Breast Cancer in the News

3D Mammography The Key to Dense Breast Screening

3D imaging aids in earlier detection of breast cancer while reducing false alarms
By Richard Budde Jr.

The latest 3D technology is no longer just for televisions and movie theaters. Tomosynthesis, commonly known as 3D mammography, is giving breast imaging specialists another tool in the early detection of breast cancer.

Tomosynthesis is similar to a routine mammogram, but instead of capturing two stationary images per breast, the 3D unit acquires multiple low dose images of each breast.
Using tomosynthesis, breast imaging experts can view complex, overlapping breast tissue one layer at a time, as opposed to the flat or two dimensional image created by traditional digital mammography.

For the patient, the experience of getting a mammogram with tomosynthesis is similar to that of a traditional digital mammogram. The length of the exam is about the same and the breast images are still transmitted electronically to the physician. The main difference is the X-ray arm of the mammography machine moves around the patient in a short arc while taking a group of low dose images in just a matter of seconds.

Moreover, tomosynthesis is especially useful for women with mild to extremely dense breast tissue. The additional slices or images provide a more thorough view of the breast tissue, enabling breast imaging specialists to see more clearly the previously obscure details on 2D mammography. Research has shown that tomosynthesis improves cancer detection in patients with dense breasts by up to 30 percent.

Breast density is measured based on the American College of Radiology's BI- RADS breast composition categories. There are four density types: "A" designates entirely fatty breast tissue and "D" indicates extremely dense breast tissue. It is generally agreed that approximately 90 percent of women fall into density categories B, C and D.

While tomosynthesis received FDA approval for use in the U.S. in 2011, it is now becoming more readily available, as more research findings are released supporting its benefits.
Studies have shown that tomosynthesis, in combination with traditional full field 2D digital mammography, can reduce false positive biopsy results by up to 15 percent as well as significantly increase cancer detection rates, including up to 40 percent more invasive cancers.

Research has also shown the more detailed imaging provided by tomosynthesis can reduce callbacks for additional testing by approximately 30 percent, thus eliminating anxiety and inconvenience for many patients.

Annual mammograms are recommended for women over 40 (or sooner for patients with a strong family history of breast cancer), regardless of the degree of breast tissue density. Regular monthly self exams and an annual clinical breast exam are also recommended. While 3D mammography is a significant emerging technology for breast imaging experts, full field digital mammography (2D) continues to be widely effective and remains the current standard of care.

By Dr. Richard Budde, Jr., is a breast imaging specialist with KentuckyOne Health Breast Care at Saint Joseph East.

Read more here:

Specific Research Aimed at Metastatic Disease

Metastatic breast cancer kills over 40,000 women a year. While there is vast research on detection, treatment and management of early disease, metastatic disease receives the least amount of funding. Since our founding in 2007, the No Surrender Breast Cancer Foundation has deeply respected the work being done at the Cold Spring Harbor Laboratory. We still do.

Today, they announced a new research grant specifically targeting how cancer cells return after chemotherapy is over.

We are proud to support all the work at CSHL and encourage all of our readers to support them as well.

"Metastatic disease is what kills people. If we can stop metastasis, then we can cut the cancer mortality rate."

LI Researcher Wins Grant to Solve a Cancer Mystery
Originally published: June 14, 2014 NEWSDAY
By Delthia Ricks

Months to years after cancer treatment has seemed effective, some malignancies come back -- rebounding with a vengeance and spreading to distant sites.

Understanding how and why potent treatments are rebuffed in certain breast cancers underlies a series of groundbreaking studies at Cold Spring Harbor Laboratory overseen by Dr. Mikala Egeblad, who late last week won a highly coveted $2.5 million research award from the Department of Defense.

The grant will aid in her efforts to find out why some breast cancers spread.

"This will really help in speeding it up," Egeblad, 43, said of her work and the additional scientists she will be able to bring onboard to delve deeper into a critical question: How cancers reseed themselves.

Known as the The Era of Hope Scholar Award, the grants are aimed at scientists still in their early career years. The defense department has been funding investigations through its Breast Cancer Research Program since 1992.

Four other scientists won grants out of more than 50 who applied for this year's awards.
Egeblad is exploring the phenomenon scientists call resistance, a cancer's capacity to repel chemotherapy. An estimated 40,000 people nationwide are affected annually by breast cancers that become resistant to treatment.

In her Cold Spring Harbor lab, Egeblad has found that a patient's own immune system cells known as macrophages play a key role in sending subversive signals that are used by tumor cells to spread.

Normally, macrophages -- chubby cells with a big mouth-like orifice -- are friends, not foe. They gobble up dead tumor cells and virtually any kind of debris, including infectious organisms. Picture the old Pac-Man video game that consumed dots.

But macrophages, Egeblad said, also send signals in the vast communication network of the body allowing cells to "talk" to each other.

"What we found is that when you give chemotherapy, the macrophages come in and clean up all these dead cells but they are also sending signals to the [tumor] cells that are not killed in the first round of chemo. And those signals are making it easier for the tumor to bounce back after chemo," she said.

Precisely what those signals are, no one knows. Egeblad is trying to decode them. She has developed a highly innovative microscopic technique that is allowing her to view -- in mice -- the activity of macrophages in real time.

Egeblad said she consulted with breast cancer survivors to better hone her work toward critical problems patients face.

One of the survivors, Joanne Marquardt of the West Islip Breast Cancer Coalition, said by zeroing in on resistant cancer cells, Egeblad is helping to unlock a critical mystery.

"Metastatic disease is what kills people," Marquardt said of cancer's spread. "If we can stop metastasis, then we can cut the cancer mortality rate."

"Right now we are getting much longer survival periods, but if you look at the mortality rates and statistics, most of the [cancer] mortality occurs in patients with metastatic disease."

Marquardt, a North Babylon resident, is a past consumer member of the Defense Department’s Breast Cancer Research Program. She has evaluated other researchers’ work and said she was excited to learn Egeblad, who lives in Cold Spring Harbor, had won a grant.

"Mikala is very humble," Marquardt said, but added her investigations are cutting-edge and she is a rising star among cancer researchers.

Your Heart: After Cancer

Important information about chest radiation and heart disease.

We have warned about this in the past, but a new study confirms earlier ones.

Bottom line: Keep an eye on your cholesterol, it elevates after chemotherapy; exercise at least 5 times a week; keep your weight down. Make sure you have your cholesterol checked when you go to your oncologist (since you probably see that doc more than any other one)

Risk of Ischemic Heart Disease in Women after Radiotherapy for Breast Cancer
Sarah C. Darby, Ph.D., Marianne Ewertz, D.M.Sc., Paul McGale, Ph.D., Anna M. Bennet, Ph.D., Ulla Blom-Goldman, M.D., Dorthe Brønnum, R.N., Candace Correa, M.D., David Cutter, F.R.C.R., Giovanna Gagliardi, Ph.D., Bruna Gigante, Ph.D., Maj-Britt Jensen, M.Sc., Andrew Nisbet, Ph.D., Richard Peto, F.R.S., Kazem Rahimi, D.M., Carolyn Taylor, D.Phil., and Per Hall, Ph.D.
N Engl J Med 2013; 368:987-998
March 14, 2013DOI: 10.1056/NEJMoa1209825

Radiotherapy for breast cancer often involves some incidental exposure of the heart to ionizing radiation. The effect of this exposure on the subsequent risk of ischemic heart disease is uncertain.

We conducted a population-based case–control study of major coronary events (i.e., myocardial infarction, coronary revascularization, or death from ischemic heart disease) in 2168 women who underwent radiotherapy for breast cancer between 1958 and 2001 in Sweden and Denmark; the study included 963 women with major coronary events and 1205 controls. Individual patient information was obtained from hospital records. For each woman, the mean radiation doses to the whole heart and to the left anterior descending coronary artery were estimated from her radiotherapy chart.

The overall average of the mean doses to the whole heart was 4.9 Gy (range, 0.03 to 27.72) Rates of major coronary events increased linearly with the mean dose to the heart by 7.4% per gray (95% confidence interval, 2.9 tp 14.5 with no apparent threshold.

The increase started withing the first 5 years after radiotherapy and continued into the third decade after radiotherapy. The proportional increase in the rate of major coronary events per gray was similar in women with and women without cardiac risk factors at the time of radiotherapy.

Exposure of the heart to ionizing radiation during radiotherapy for breast cancer increases the subsequent rate of ischemic heart disease. The increase is proportional to the mean dose to the heart, begins within a few years after exposure, and continues for at least 20 years. Women with preexisting cardiac risk factors have greater absolute increases in risk from radiotherapy than other women. (Funded by Cancer Research UK and others.)

Supported by funding to the Oxford University Clinical Trial Service Unit from Cancer Research UK, the British Heart Foundation, and the U.K. Medical Research Council and by grants from the European Commission (FI6R-012796), the U.K. Department of Health (RRX 108), the British Heart Foundation Centre for Research Excellence (CRE RE/08/004, to Dr. Cutter), and the Oxford National Institute for Health Research Biomedical Research Centre (to Dr. Rahimi).

Disclosure forms provided by the authors are available with the full text of this article at
No potential conflict of interest relevant to this article was reported.
We thank research nurses Ann-Sofie Andersson and Milka Krestelica in Sweden and Liselotte Jeppesen in Denmark for data abstraction; and Ulrich H. Koehler in Denmark for data management.
Source Information
From the Clinical Trial Service Unit (S.C.D., P.M., D.C., R.P., C.T.) and the George Centre for Healthcare Innovation (K.R.), University of Oxford, Oxford, and the Department of Medical Physics, Royal Surrey County Hospital and Surrey University, Guildford (A.N.) — both in the United Kingdom; the Department of Oncology, Odense University Hospital, Institute of Clinical Research, University of Southern Denmark, Odense (M.E.), the Oncology Department, Aalborg Hospital, Aalborg (D.B.), and the Danish Breast Cancer Cooperative Group, Rigshospitalet, Copenhagen (M.-B.J.) — all in Denmark; the Department of Medical Epidemiology and Biostatistics (A.M.B., P.H.) and the Division of Cardiovascular Epidemiology, Institute of Environmental Medicine and Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd Hospital (B.G.), Karolinska Institutet, and the Departments of Oncology (U.B.-G.) and Medical Physics (G.G.), Karolinska University Hospital — all in Stockholm; and the H. Lee Moffitt Cancer Center and Research Institute, University of Southern Florida, Tampa (C.C.).
Address reprint requests to Dr. Darby at the Clinical Trial Service Unit, Richard Doll Bldg., Old Road Campus, Oxford OX3 7LF, United Kingdom, or at

UAlberta medical researchers find DNA marker that predicts breast cancer recurrence
January 16, 2013

Medical researchers at the University of Alberta tested the DNA of more than 300 women in Alberta and discovered a ‘genetic marker’ method to help accurately profile which women were more apt to have their breast cancer return years later.

Sambasivarao Damaraju, a professor with the Faculty of Medicine & Dentistry, and at the Cross Cancer Institute just published his team’s
findings in the peer-reviewed journal, PLoS One.  Using a simple blood test, Damaraju and his team, which included his PhD student Yadav Sapkota, scanned the entire human genome of 369 women who had been diagnosed with breast cancer. Of those, 155 had their cancer come back and 214 did not.

“If we can accurately predict which women are at high risk of breast cancer recurrence, it gives the physicians and oncologists treating those women time to design a more aggressive therapy in hopes of preventing the cancer from coming back,” says Damaraju, who works in the Department of Laboratory Medicine & Pathology. “Treatment strategies could be tailor made for these women based on their genetic make-up and how susceptible it makes them to breast cancer recurrence.”

Damaraju and his team focused their research on good prognosis breast cancer – cancer that has a high success rate in terms of initial recovery and treatment. About 70% of all breast cancers fall into this category. Yet despite the high success rate with initial treatment for this type of breast cancer, the overall numbers of those who died or had their cancer spread in this ‘good prognosis’ group are substantial. The numbers are high simply because so many people have this common ‘good prognosis’ cancer.

Currently, treatment options for breast cancer patients are based on what doctors know about the tumour itself – its size, grade and the absence or presence of certain markers within the tumour. Damaraju noted there are patients who are given an excellent prognosis based on what doctors see within the tumour, yet the cancer comes back. And other women remain cancer free even though their doctors said they had a poor prognosis based on information gleaned from the tumour. Damaraju thinks that this inaccuracy of tumor based markers could be complimented with this DNA marker that can be found through a simple blood test.

Damaraju and his team are continuing their research in this area and would like to reconfirm their findings in a larger study, pending further funding. The results from that study could be published in about three years, and he suspects about two years after that, the DNA predictor test could be tested in prospective clinical studies prior to making them widely available for women.
The research was funded by the Canadian Breast Cancer Foundation – Prairies/NWT region, and the Alberta Cancer Foundation.

“The impact of Dr. Damaraju’s significant discovery on personalized treatment for breast cancer patients is substantial,” says Canadian Breast Cancer Foundation – Prairies/NWT Region CEO Trish Bronsch. “Knowing individual risks of breast cancer and reccurrence provides doctors and oncologists with a better picture in which they can create a treatment plan to fit personal needs. We are very excited to have been able to help fund Dr. Damaraju and his team to this discovery.”
The Alberta Cancer Foundation agreed.

“We are pleased to see donor dollars having a direct impact on outcomes that are important to Albertans--in this case earlier detection and improved treatment options for breast cancer recurrence,” says Myka Osinchuk, CEO of the Alberta Cancer Foundation. “We are excited to follow Dr. Damaraju and his team to ensure those women successfully treated for breast cancer continue to live cancer-free lives.”

2012 SABCS News: Triple Negative Breast Cancer Identified as Androgen Positive breast cancer may open door for Prostate Cancer drug to treat it… read more

Natural Weapon Against Triple Negative Breast Cancer
Something so simple.... nature healing nature.... Will this be the answer like mold was to penicillin?

Oncolytic Virus Kills Tumor in Triple-Negative Breast Cancer
Caroline Helwick, Medscape

October 25, 2011 (San Francisco, California) — Laboratory studies conducted at the Memorial Sloan-Kettering Cancer Center in New York City suggest that triple-negative breast cancer (TNBC) might respond to treatment with an oncolytic agent.

The findings were reported here at the American College of Surgeons 97th Annual Clinical Congress.
"We found that [the mutant herpes virus] NV1066 is an effective oncolytic agent against triple- negative breast cancer in vitro and in vivo," said Sepideh Gholami, MD, a research fellow in the laboratory of Yuman Fong, MD, which is considered to be at the forefront in oncolytic viral therapy research.

"Oncolytic viruses are attractive therapeutic agents that destroy tumor cells without the accompanying destruction of normal cells," she said. The mitogen-activated protein kinase (MAPK)signaling pathway is known to be important in TNBC, and activated (phosphorylated) MAPK signaling has been shown to mediate efficient replication of NV1066 through the deletion of the delta gamma(1)34.5 gene.

In other words, she said, TNBC cells have high levels of phosphorylated MAPK, a protein that promotes tumor growth and contributes to resistance to current therapies. The herpes virus specifically targets cells that overexpress this protein, which is the rationale for this approach. The study aimed to determine whether NV1066 could kill TNBC cells effectively. The researchers also examined the functional effects of NV1066 on the MAPK signal transduction pathway during viral infection.

Dr. Gholami and colleagues infected 5 different TNBC cell lines with the NV1066 herpes simplex virus. After treatment with the virus, the most sensitive cell lines demonstrated a 90% cell kill rate within 1 week; the less sensitive lines demonstrated a 70% cell kill rate.

In addition, sensitive cell lines expressed higher baseline levels of phosphorylated MAPK than resistant cell lines, and viral infection caused the downregulation of phosphorylated MAPK by 48 hours, she reported.

"TNBC cells support efficient viral replication, with over 1 million copy numbers observed, which is more than a 1000-fold increase," she said.
"Since baseline phosphorylated MAPK levels positively correlated with sensitivity to NV1066, they might therefore be used as a clinical marker for selecting patients for viral therapy," she suggested.

Tumor Regression Almost Complete
The researchers created flank tumors and injected them with NV1066 or a control compound. Within 5 days, tumor volume significantly decreased in the experimental group; within 3 weeks, they observed "near-complete tumor regression," Dr. Gholami reported.

Proof Positive: Regular Mammograms, Especially Early Ones, Save Lives. Period.

ABC has just released the report out of Sweden that regular mammograms, particularly those starting young, save lives. There is no question about it. So the next time your doctor tells you that you are "too young" or your breast are "too dense" or that the ACS or Komen do not recommend early, regular screenings- refer them to this report.

The No Surrender Breast Cancer Foundation is dedicated to providing the vital information to young women. This study proves that not only those at risk for Triple Negative Breast Cancer will be saved, but those who will go on to develop slower growing, estrogen responsive tumors will have fewer deaths through early, long-term screening. It is imperative  to GET SCREENED BEFORE THE AGE OF FORTY and continue yearly follow-up.

We can't do it alone. Studies like this will help us. You need to help us too. Spread the word. Donate to our foundation so we have the funds to get the message out there.

We can no longer afford to have these so-called breast cancer groups dictating when a woman "should" be screened. It is a matter of surviving the disease for a long period of time over finding a tumor that is too far gone to be stopped.

Think about this, please. And if you can, help support us.

Thank you.

Mammograms Reduce Breast Cancer Deaths, Period -- Swedish Study Finds
June 28, 2011
Mammograms save lives, period, end of story. But it takes decades to appreciate just how many.
That's the takeaway from the longest-running mammogram study -- which followed more than 100,000 Swedish women for 29 years -- that many doctors believe will put the recent ruckus over the frequency of breast cancer screening to bed.

The researchers found that seven years of mammograms made for 30 percent fewer breast cancer deaths years down the road, when compared with women who didn't receive mammograms.

"I think this study indicates the absolute benefit of screening in terms of breast cancer deaths prevented," says Stephen Duffy, a professor of cancer screening at Queen Mary, University of London, and lead author of the study.

While the American Cancer Society had long recommended that women over the age of 40 receive yearly mammograms, the U.S. Preventive Services Task Force challenged this recommendation in 2009, calling into question whether the number of lives saved were worth the cost of such regular mammograms and the increased possibility of false positives. In light of the possible adverse effects of yearly screening, the Task Force recommended that women get screened every other year starting at age 50, and stop mammogram screening altogether after age 75.

But the Swedish study, published Tuesday in the Journal Radiology, suggests that when women are followed over the course of decades (in this case 29 years) instead of the seven or so years that many past studies have looked at, mammograms may save many more lives.

Among the 133,065 women studied, one breast cancer death was prevented for every 414 to 519 women screened.

"The longer follow-up period, three decades, is crucial. It is important to have this length of time to allow the benefits of screening to become apparent," says Dr. Laurie Margolies, chief of breast imaging at Mount Sinai Medical Center in New York, who was not involved in the Swedish study.

This long-term view is important, in part because certain types of breast cancer can take decades to become lethal, says Dr. Richard Ellis, co-director of the Norma J. Vinger Center for Breast Care in Wisconsin.

"A less aggressive, slow-growing cancer could take 15 to 25 years before it spreads to a vital organ, resulting in a breast cancer death," he says. "Thus, a shorter-term follow-up study will likely account only for breast cancer deaths due to the more aggressive cancers. … That is why studies with shorter follow-up … understate the true value of screening mammography."

The Swedish Study and Mammogram Debate
The recent study looked at more than 100,000 women in two counties in Sweden. Beginning in 1977, researchers randomly assigned half the women to receive seven years of regular medical care that did not include mammograms, and the other half to receive regular mammograms -- every two years for those age 40 to 49 and every three years for those age 50 to 74.

When the seven-year trial ended, the researchers followed up with the women for 22 more years. After seven years, all the women were offered mammograms, but only those cancers detected during those first seven years were included in the study's results.

The researchers found that the preventive effect of mammograms became more apparent as the years went by: 10 years after the study began, 71 lives had been saved because of the screenings; 29 years later, 158 lives had been saved, study leader Duffy says.
The Value of Regular Screening

Critics of frequent mammograms have generally focused on the relatively few lives saved per thousands of screenings.

According to a 2009 analysis published in the Cochrane Collection, an international health care network, one in 2,000 women will have her life prolonged by 10 years because of a mammogram, but another 10 healthy women will undergo unnecessary breast cancer treatment, and 200 women will endure significant psychological stress because of a false positive result -- they'll be erroneously told they have breast cancer when they don't.

The researchers who studied the Swedish women challenge such findings, suggesting that it takes nearly half as many mammograms to save a life, perhaps fewer if mammograms were given continually throughout middle and old age -- a rate of prevention that study leader Duffy and other breast cancer experts argue makes screenings worth the risk of possible adverse effects from radiation and false positives.

For every 1,000 to 1,500 mammograms given in this study, one breast cancer death was prevented, and if the initial screening period had lasted 10 years instead of seven, only 300 screenings would have been needed to save one life, the researchers reported.

And this was found in a population that received mammograms half as frequently as the American Cancer Society currently recommends for women in the U.S. If the Swedish women had been screened every year instead, there would have been a more "dramatic" reduction in the number of breast cancer deaths, says Dr. Peter Jokich, head of the mammography Center at Rush University Medical Center in Chicago.

Overall, breast cancer experts believe this study out of Sweden supports the message they've been sending all along: Regular mammograms save lives. Period.

Is Your Chemo Working? A New Test
A Genomic Predictor of Response and Survival Following Taxane-Anthracycline Chemotherapy for Invasive Breast Cancer
JAMA. 2011 May 11;305(18):1873-1881, C Hatzis, L Pusztai, V Valero, DJ Booser, L Esserman, A Lluch, T Vidaurre, F Holmes, E Souchon, H Wang, M Martin, J Cotrina, H Gomez, R Hubbard, JI Chaco´n, J Ferrer-Lozano, R Dyer, M Buxton, Y Gong, Y Wu, N Ibrahim, E Andreopoulou, NT Ueno, K Hunt, W Yang, A Nazario, A DeMichele, J O’Shaughnessy, GN Hortobagyi, WF Symmans

Predictive tests for response to chemotherapy by patients with newly diagnosed breast cancer are needed so that appropriate chemotherapy decisions may be made. To date, molecular tests do not provide predictive superiority over the combination of standard clinicopathologic parameters. This study evaluated the strength of a genomic test for predicting response and survival in patients with breast cancer following sequential taxane and anthracycline chemotherapy, using a predictive algorithm based on sensitivity to adjuvant endocrine therapy, resistance to chemotherapy, and chemosensitivity.

Tumor biopsy samples obtained prior to systemic therapy were used for genomic studies to identify potential predictors of treatment outcome. Predictors were identified using gene expression microarrays to compare expression in samples from patients with higher risk in two responder groups (pathologic complete response or minimal residual cancer burden [RCB-I] vs moderate or extensive residual cancer burden [RCB-II/III]) in ER-negative and -positive subgroups.

Biopsy samples were obtained from 310 patients in the discovery cohort and 198 patients in the validation cohort. Patients in the validation cohort had clinical response rates of 25% (pathologic complete response) and 30% (pathologic complete response or RCB-1), and distant relapse-free survival (DRFS) rates at 3 years of 79%.

After excluding patients with predicted endocrine sensitivity, the chemopredictive test algorithm had a positive predictive value (PPV) of 56% (95% CI, 31%–78%). In the 28% of patients predicted to be treatment sensitive, the 3-year DRFS was 92% (95% CI, 85%–100%), with an absolute risk reduction (ARR) of 18% (95% CI, 6%–28%). In the patients predicted to be treatment insensitive, the 3-year DRFS was 75% (95% CI, 67%–82%), with a PPV of 25% and odds ratio for relapse of 4.01 (95% CI, 1.60–20.4). There was a significant association of predicted sensitivity to treatment and improved DRFS (P = .002). Among patients predicted to be treatment sensitive, the diagnostic likelihood ratio for occurrence vs absence of 3-year distant relapse or death was 0.33 (95% CI, 0.07–0.72).

Patients predicted to be treatment sensitive had 3-year DRFS (92%) similar to that of patients who achieved pathologic complete response after completing neoadjuvant chemotherapy (93%). In addition, patients predicted to be treatment insensitive had 3-year DRFS (75%) identical to that of patients with residual disease.

In the 30% of patients with ER-positive disease who were predicted to be treatment sensitive, 3-year DRFS was 97% (95% CI, 91%–100%) and ARR was 11% (95% CI, 0.1%–21%). In patients with ER-positive disease who were predicted to be treatment insensitive, the PPV for 3-year DRFS was 14% (95% CI, 6%–21%). A total of 26% of patients with ER-negative tumors were predicted to be treatment sensitive. In these patients, 3-year DRFS was 83% (95% CI, 68%–100%), with ARR of 26% (95% CI, 4%–48%) and PPV for pathologic response of 83% (95% CI, 36%–100%). In contrast, patients who were ER-negative and predicted to be treatment insensitive had a PPV for 3-year relapse of 43% (95% CI, 28%–55%). In patients predicted to be treatment sensitive, the test had a significant diagnostic likelihood ratio for predicted occurrence vs absence of 3-year distant relapse or death of 0.27 (95% CI, 0.01-0.94) in patients who were ER-positive and 0.35 (95% CI, 0.04–0.91) in those who were ER-negative. The type of taxane therapy was not associated with predicted treatment sensitivity and DRFS.

After adjusting for standard clinicopathologic parameters, genomic predictions were independently and significantly associated with risk of distant relapse or death (sensitive vs insensitive: hazard ratio [HR], 0.19; 95% CI, 0.07–0.55; P = .002). The predictive utility of a multivariate Cox model of clinicopathologic factors (tumor stage and ER status) was increased with the addition of the genomic prediction (likelihood ratio, 13.8; P < .001). Other previously published genomic predictors were also significantly predictive of pathologic response in the discovery and validation cohorts, but, paradoxically, predicted worse DRFS in patients predicted to be treatment sensitive.

There was a clinically meaningful survival difference between patients predicted to be treatment sensitive and those predicted to be treatment insensitive. The predictive test in this study improved on the predictions based on clinicopathologic parameters.


Radioactive Seed Localization Guides Surgeons to Nonpalpable Breast Lesions
Elsevier Global Medical News. 2011 May 11, MG Sullivan

WASHINGTON (EGMN) - Radioactive seeds were a safe and effective method of pinpointing nonpalpable breast lesions for surgery, with an 85% rate of negative margins on the first excision and an ipsilateral recurrence rate of less than 2% over 33 months, according to a large retrospective study.

Close margins occurred in 12% of the 767 patients with nonpalpable breast lesions, and positive margins occurred in 3%. The overall re-excision rate was 15%, Dr. Lee McGhan of the Mayo Clinic, Scottsdale, Ariz., said at the annual meeting of the American Society of Breast Surgeons.

Performing the procedure is "almost intuitive," with a very low learning curve, he said. "It is now our method of choice when dealing with preoperative localization of nonpalpable breast lesions."

His retrospective review of 978 prospectively collected patient records comprised 1,000 radioactive in 2003-2010. Almost 1,150 seeds were deployed.

The patients' mean age was 65 years; their mean lesion size was 1.2 cm. Most (550) had an invasive carcinoma; 217 had DCIS (ductal carcinoma in situ); 115 had atypical hyperplasia, and the remainder, uncertain or suspicious percutaneous biopsy results.

Dr. McGhan reported 33-month follow-up results on the 767 women with either invasive carcinoma or DCIS. Most patients (910) received just one seed; 84 received two seeds; 5 received three seeds; and 1 patient received four of the devices.

Most (76%) underwent the procedure at least 1 day before surgery. Typically, Dr. McGhan said, patients came to the clinic a few days before surgery for an evaluation. Many chose to have the localization on a Friday, stayed over the weekend, and had the seeds removed early on Monday morning.

The 4- to 5-mm seeds containing radioactive iodine-125 can be placed up to 5 days before surgery. They were deployed through an 18-gauge spinal needle under image guidance; post deployment, a mammogram or ultrasound confirmed their position near the lesion. "We used a handheld gamma probe to identify the area of greatest radioactivity at the skin surface, marking the optimal site of skin incision," Dr. McGhan said.

Intraoperative complications included 30 displaced seeds - including 3 suctioned up by operative tubing and 3 that were improperly deployed during radiology - as well as one instance of an incorrect incision site resulting from a miscommunication between the radiologist and the surgeon, Dr. McGhan said. All of these seeds were retrieved with no patient harm.

All of the localized lesions were successfully removed, along with their associated seeds; the specimens were sent to pathology. Among the 550 invasive cancers, margins were negative in 87%, close in 9%, and positive in 3%. Re-excision was required in 13% (69).

Among the 217 DCIS lesions, margins were negative in 77%, close in 19%, and positive in 3%. Re-excision was necessary in 23% (49).

Sentinel node biopsies occurred in 544 cases, and were successful in all but one, Dr. McGhan said. "There was no blue dye detected, which was determined to be due to tumor invasion of the lymphatics rather than a direct complication of the procedure."

The mean follow-up period was 33 months. Over this time, the overall ipsilateral recurrence rate was 1.6% (12 patients). The rate was slightly higher among patients with DCIS (3%; seven patients). The local recurrence rate was 1% (five patients) among those with invasive cancer. By the end of the follow-up period, there were six mastectomies secondary to recurrence: three (0.5%) in the invasive cancer group and three (1%) in the DCIS group.


ASBS: Mammogram Studies Suggest Use in Younger Women
By Charles Bankhead, Staff Writer, MedPage Today
May 03, 2011

WASHINGTON -- Excluding younger women from routine screening mammography
may increase the risk of larger, more advanced tumors at diagnosis and adversely
affect survival, data from a retrospective chart review suggested.
Among women younger than 50, tumors diagnosed by means other than
mammography were 50% larger and three times as likely to have lymph node
involvement, according to Paul S. Dale, MD, of the University of Missouri in
Columbia, and colleagues.

The risk of recurrence was almost six times higher, and both disease-free and overall
survival were substantially lower among women who did not have mammographically
detected cancer.

"Mammography detected cancers in women ages 40 to 49 that were smaller, had
less nodal metastasis, and were associated with increased survival," Dale said here
during a press briefing at the American Society of Breast Surgeons meeting.
"Excluding women in this age group from routine mammograms will potentially result
in later disease diagnosis and poorer survival rates for women ages 40 to 49."
Another study reported at the meeting suggested that failure to perform routine
mammography in younger women may miss opportunities for early diagnosis of
hormone-receptor positive, HER2-negative, and triple-negative tumors, particularly
among women of minority groups.

In 2009 the U. S. Preventive Services Task Force (USPSTF) ignited a firestorm of
controversy with revised breast cancer screening recommendations that encouraged
individualized decision making about mammography for women ages 40 to 49.
Previously, annual screening had been the norm for all women, beginning at age 40.
Almost immediately, proponents of annual screening at age 40 criticized the
recommendation for creating confusion and putting younger women at increased risk.
Played out largely in the media, the arguments and counterarguments reached a
point of such contention that HHS Secretary Kathleen Sebelius found it necessary to
release a statement emphasizing that the USPSTF does not set health policy.
The studies reported at the ASBS meeting approached the controversy from a "what
if" perspective, examining potential risks and consequences if younger women
diagnosed with breast cancer had been omitted from routine mammographic

"Breast cancer mortality rates have been declining since 1990," said Dale. "Mortality
rates have significantly decreased in women younger than 50, and this decrease has
been attributed to earlier detection of presymptomatic breast cancer through

To examine potential consequences of not screening younger women, Dale and his
team reviewed breast cancer records for a 10-year period and identified women
whose disease was diagnosed before age 50.

The review resulted in a study population comprising 145 women with
mammographically detected breast cancer and 166 whose cancer was diagnosed by
other means.

Comparison of the two groups showed that nonmammographically detected breast
cancer had a strong association with high-risk features:
Larger size, 30.38 mm versus 20.68 mm
Nodal involvement, 85 (56%) versus 28 (25%)
Positive family history, 38 (25%) versus 19 (15%)
Recurrence, 40 (23.4%) versus 7 (5%)
Additionally, women with mammographically detected breast cancer had a five-year
disease-free survival of 94% versus 71% for nonmammographically detected cancer
and overall survival of 97% versus 78%.

Even when detected at an early stage, breast cancer in younger women tends to be
higher risk, data from the second study showed.

Those findings came from an analysis of 46,700 women who had diagnoses of ductal
carcinoma in situ (DCIS) or T1N0 breast cancer included in the California Cancer
Registry from 2004 to 2008.

The study population included 10,566 women ages 40 to 49 (22.6% of the total), said
Sharon Lum, MD, of Loma Linda University in California.
Comparison of clinical and demographic features of younger (40 to 49) and older (50
to 74) patients showed that the cancers in younger women were significantly more
likely to be:
Hormone receptor positive, OR 1.85 (DCIS) and OR 1.43 (T1)
HER2 positive, OR 1.46 (T1)
Triple negative, OR 1.67 (T1)
Younger women with DCIS or T1 disease were significantly more likely to be from
minority racial/ethnic groups (OR 1.44 to OR 1.82).

Excluding women ages 40 to 49 from mammographic screening could affect early
diagnosis of high-risk cancers and would disproportionately affect minorities, possibly
leading to diagnosis of more advanced-stage disease, said Lum.

Primary source: American Society of Breast Surgeons
Source reference:
Dale P, et al "Mammography in 40-year-old women: The potential impact of the U.S.
Preventative Services Task Force (USPSTF) mammography guidelines" ASBS 2011;
Abstract 1754.
Additional source: American Society of Breast Surgeons
Source reference:
Aragon RJ, et al "The potential impact of USPSTF recommendations on the early
diagnosis of breast cancer" ASBS 2011; Abstract 1670.
© 2004-2011 MedPage Today, LLC. All Rights Reserved.

New Drug Combo for Metastatic Disease

An early-phase study showed that the new taxoid, cabazitaxel (XRP6258), is not only safe but has significant activity when combined with capecitabine in patients with metastatic breast cancer previously treated with paclitaxel-like agents. This is a new drug combo with great promise that women who have Stage 4 disease can use in their arsenal against their cancer.

Eur J Cancer. 2011 May 1;47(7):1037-1045, C Villanueva, A Awada, M Campone, JP Machiels, T Besse, E Magherini, F Dubin, D Semiond, X Pivot

Background: Most patients with metastatic breast cancer (MBC) progress after chemotherapy. Cabazitaxel (XRP6258) is a new taxoid that is active in chemotherapy-resistant tumour cell lines. The objectives of this phase I/II study were to assess the maximum tolerated dose (MTD), safety profile, pharmacokinetics, and activity of cabazitaxel plus capecitabine in patients with MBC who had been previously treated with taxanes and anthracyclines.

Patients and Methods: In part I, we used a 3 + 3 dose–escalation scheme to assess the MTD of intravenous cabazitaxel (day 1) with oral capecitabine twice daily (days 1–14) every 3 weeks. In part II, we evaluated the objective response rate (ORR) at the MTD.

Results: Thirty-three patients were enrolled and treated (15 in part I; 18 in part II). Cabazitaxel 20 mg/m2 plus capecitabine 1000 mg/m2 was the MTD. Pharmacokinetic analysis showed no apparent drug–drug interaction. In all patients, the main grade 3–4 toxicities were asthenia (n = 5), hand–foot syndrome (n = 5), neutropenia (n = 21), neutropenic infection (n = 1), and neutropenic colitis (n = 1). One patient had febrile neutropenia. Antitumour activity was observed at all dose-levels with two complete responses, five partial responses (PRs), and 20 disease stabilisations (seven unconfirmed PR). At the MTD, 21 patients were evaluable for efficacy. The ORR was 23.8% (95% CI: 8.2–47.2%). The median response duration was 3.1 months (95% CI: 2.1–8.4 months), with four of five lasting for more than 3 months. Median time to progression was 4.9 months.

Conclusions: Cabazitaxel combined with capecitabine is active, has a safety profile consistent with a taxane plus capecitabine combination and warrants further investigation in patients with MBC.

Breaking the Code

The next time someone asks, "Where is the cure?" consider the following: Breast cancer is not one disease. Further, as new research clearly illuminates, its mutations are multitudinous.

Genomic research into the DNA of breast cancer cells will lead us to better treatments, however, it will be a long time before a cure can be found. But they are certainly getting closer, however long the road ahead may be - God's Speed, dear researchers!

DNA of 50 breast cancer patients decoded
Published: Saturday, April 2, 2011 - 09:33 in Health & Medicine
Matthew J. Ellis, MD, PhD

In the single largest cancer genomics investigation reported to date, scientists have sequenced the whole genomes of tumors from 50 breast cancer patients and compared them to the matched DNA of the same patients' healthy cells. This comparison allowed researchers to find mutations that only occurred in the cancer cells. They uncovered incredible complexity in the cancer genomes, but also got a glimpse of new routes toward personalized medicine. The work was presented at the American Association for Cancer Research 102nd Annual Meeting 2011.

In all, the tumors had more than 1,700 mutations, most of which were unique to the individual, says Matthew J. Ellis, MD, PhD, professor of medicine at Washington University School of Medicine in St. Louis and a lead investigator on the project.

"Cancer genomes are extraordinarily complicated," Ellis says. "This explains our difficulty in predicting outcomes and finding new treatments."

To undertake the massive task, Washington University oncologists and pathologists at the Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine collaborated with the university's Genome Institute to sequence more than 10 trillion chemical bases of DNA — repeating the sequencing of each patient's tumor and healthy DNA about 30 times to ensure accurate data.

"The computing facilities required to analyze this amount of data are similar in scale to those of the Large Hadron Collider, used to understand the workings of sub-atomic particles," Ellis says.
The DNA samples came from patients enrolled in a clinical trial that Ellis is leading for the American College of Surgeons Oncology Group. All patients in the trial had what is called estrogen-receptor-positive breast cancer. These cancer cells have receptors that bind to the hormone estrogen and help the tumors grow.

To slow tumor growth and make the tumors easier to remove, patients received estrogen-lowering drugs before surgery. But, for unknown reasons, this treatment does not always work. Twenty-four of the 50 tumor samples came from patients whose tumors were resistant to this treatment, and 26 came from patients whose tumors responded. Comparing the two groups might help explain why some estrogen-receptor-positive breast cancer patients do well with estrogen-lowering drugs and others poorly.

Confirming previous work, Ellis and colleagues found that two mutations were relatively common in many of the patients' cancers. One called PIK3CA is present in about 40 percent of breast cancers that express receptors for estrogen. Another called TP53 is present in about 20 percent.

Adding to this short list of common mutations, Ellis and colleagues found a third, MAP3K1, that controls programmed cell death and is disabled in about 10 percent of estrogen-receptor-positive breast cancers. The mutated gene allows cells that should die to continue living. Only two other genes, ATR and MYST3, harbored mutations that recurred at a similar frequency as MAP3K1 and were statistically significant.

"To get through this experiment and find only three additional gene mutations at the 10 percent recurrence level was a bit of a shock," Ellis says.

In addition, they found 21 genes that were also significantly mutated, but at much lower rates — never appearing in more than two or three patients. Despite the relative rarity of these mutations, Ellis stresses their importance.

"Breast cancer is so common that mutations that recur at a 5 percent frequency level still involve many thousands of women," he says.

Ellis points out that some mutations that are rare in breast cancer may be common in other cancers and already have drugs designed to treat them.

"You may find the rare breast cancer patient whose tumor has a mutation that's more commonly found in leukemia, for example. So you might give that breast cancer patient a leukemia drug," Ellis says.

But such treatment is only possible when the cancer's genetics are known in advance. Ideally, Ellis says, the goal is to design treatments by sequencing the tumor genome when the cancer is first diagnosed.

"We get good therapeutic ideas from the genomic information," he says. "The near-term goal is to use information on whole genome sequencing to guide a personalized approach to the patient's treatment."

This work builds on previous collaborations between Washington University oncologists and the Genome Institute. In a study published last year in Nature, they reported the complete tumor and normal DNA sequences of a woman with "triple-negative" breast cancer, a particularly aggressive type that is difficult to treat and more common in younger women and African-Americans.

While many mutations are rare or even unique to one patient, Ellis says quite a few can be classified on the basis of common biological effects and therefore could be considered together for a particular therapeutic approach.

Ellis looks to future work to help make sense of breast cancer's complexity. But these highly detailed genome maps are an important first step.

"At least we're reaching the limits of the complexity of the problem," he says. "It's not like looking into a telescope and wondering how far the universe goes. Ultimately, the universe of breast cancer is restricted by the size of the human genome."


Five years of Tamoxifen reduces cancer: study

A study conducted by the researchers based at the Cancer Research UK and UCL Cancer Trials Centre for Tamoxifen, demonstrated that the cancer was less likely to come back in women who took the drug for five years, compared to two years.

The results of the trial, with 3,500 patients, suggested that the cancer came back in around 40% of the patients who took the medicine for five years, as compared to those who has taken Tamoxifen for two years.

According to the scientists, taking Tamoxifen for five years gives the best chance of survival from breast cancer.

Cancer Research UK Clinical Research director Kate Law said this large Cancer Research UK-funded study is the first to look at the long-term performance of Tamoxifen - considered to be one of the most important drugs in the history of breast cancer treatment.

"Our research is behind many important drugs, including Tamoxifen, that have contributed to more than three quarters of women with breast cancer now surviving their disease for ten years or more," Law said.


Drug combinations may improve triple negative breast cancer treatment
HOUSTON -- (March 21, 2011) -- Researchers led by Baylor College of Medicine have found a new way to tackle a difficult-to-treat form of breast cancer – a discovery that is being translated into human studies with currently approved FDA drugs.

The new strategy begins with their discovery that a gene called PTPN12 plays a pivotal role in triple negative breast cancer, an aggressive form of the disease that accounts for approximately 20 percent of new cases of the disease and is resistant to common drugs such as Tamoxifen and Herceptin®. Until now, the genes that drive the growth of triple negative breast cancer have been a mystery, making it difficult for scientists to devise new therapies for this disease.

In a report in a recent issue of the journal Cell, Dr. Thomas F. Westbrook of BCM and colleagues describe their new understanding of the forces that drive this aggressive disease and, more important, how to use a combination of drugs to block those forces.
PTPN12 prevents breast cancer
"This study gives us promising new insight into how to treat patients with triple negative breast cancer and possibly other cancers," said Westbrook, assistant professor of biochemistry and molecular biology and molecular and human genetics at BCM and senior author of the report.

In this study, Westbrook and his collaborator, Dr. Stephen J. Elledge of Harvard Medical School, screened literally tens of thousands of genes for their role in human breast cancer. They found that the gene PTPN12 prevents or suppresses breast cancer. Next, together with researchers at the BCM Lester & Sue Smith Breast Center, Westbrook showed that most triple negative breast cancers have lost that protective gene.

Most important, the researchers found that the loss of PTPN12 unleashes a specific combination of cancer-promoting enzymes called tyrosine kinases. These enzymes work in concert to cause aggressive growth and spread of triple negative breast cancer. Blocking just one kinase is not enough, said Westbrook. Specific combinations of kinases have to be blocked to stop the growth of the breast cancer.
Combining kinase inhibitors
Because drugs that block some of these kinases are already FDA-approved for patients, this study provides an exciting strategy for combining specific kinase inhibitors to combat triple negative breast cancer as well as other forms of cancer.

This double-barreled discovery gives researchers a new foothold from which to fight triple negative breast cancer.

"This discovery is an important advance for patients, because we may now be able to rationally combine drugs that inhibit these kinases to treat patients with triple negative breast cancer (and other cancers) that were previously thought intractable to such therapies," said Westbrook, also a member of the NCI-designated Dan L. Duncan Cancer Center.
Combos block spread
Westbrook and colleagues showed that inhibiting specific combinations of these kinases effectively blocks the growth and spread of triple negative breast cancer in animals. Because drugs that block some of these kinases are already approved for patients, this study provides an exciting strategy for combining specific kinase inhibitors to combat triple negative breast cancer as well as other forms of cancer.

Many researchers and physicians believe it will be important to combine drugs for cancer treatment," said Westbrook.

"But the strategy of which medicines to combine is difficult to predict. Here, we are providing a new rationale to combine a specific set of medicines to treat this debilitating disease, and we are now pursuing clinical trials to test this new idea."

May play role in other cancers
In addition to triple negative breast cancer, PTPN12 may play a role in other difficult-to-treat malignancies such as lung cancer. In fact, there may be a whole class of genes that behave like PTPN12 to inhibit kinases and cancer formation.

"By discovering these new genes and how they work, we think we can develop new therapies for many types of cancer," said Westbrook.

Others who took part in this study include Tingting Sun, Kristen L. Meerbrey, Jessica D. Kessler, Maria Botero, Jian Huang, Ronald J. Bernardi, Earlene Schmitt, Mitchell Rao, Chad J. Creighton, Susan G. Hilsenbeck, Chad A. Shaw, Donna Muzny, Richard A. Gibbs, David A.Wheeler, C. Kent Osborne, Rachel Schiff and Ilenia Migliaccio,, all of BCM; Nicola Aceto and Mohamed Bentires-Alj of the Friedrich Miescher Institute for Biomedical Research in Basel, Switzerland; Natalya Pavlova, Guang Hu, Mamie Li, Noah Dephoure, Steven Gygi, and Chunshui Zhou, all of Harvard Medical School, and Don Nguyen of Yale University School of Medicine.

Funding for this work came from The V Foundation and the Mary Kay Ash Foundation for Cancer Research, the Susan G. Komen for the Cure Foundation, the Special Program of Research Excellence of the National Cancer Institute, the U.S. Army and the Howard Hughes Medical Institute.
Radiation RECALL Notice
From the New York Times
March 21, 2011
Riddled With Metal by Mistake in a Study
Women participating in a study of patients with breast cancer have been inadvertently left with hundreds of tiny particles of the heavy metal tungsten in their breast tissue and chest muscles. The particles came from a device used during surgery. The device has since been recalled.

It is not known if the metal is dangerous to health because relatively little research has been done on its long-term effects in the body. But it shows up on mammograms, and may make them difficult to read, an especially troubling effect for women who have already had breast cancer and worry about recurrences. (The particles resemble calcium deposits, which can indicate cancer.)

About 30 women have been affected, according to the manufacturer of the device that caused the problem, the Axxent FlexiShield Mini. The women are in a quandary. At least one, fearing that the tungsten could cause cancer or another illness, is trying to decide whether to get rid of the particles by having her breast and its underlying tissue removed in a radical and disfiguring operation.

Twenty-seven of the cases occurred at Hoag Memorial Hospital Presbyterian in Newport Beach, Calif. Eleven of those women have had mammograms, and all 11 showed tungsten. Hospital officials declined interviews, but issued a statement acknowledging that the problem had occurred.

Two other women were treated in a study at Karmanos-Crittenton Cancer Center in Rochester Hills, Mich. A hospital spokeswoman said that both patients had been informed of the recall and the potential problem but had not returned to the hospital.

The episode casts doubt on the safeguards for people who participate in medical research and on the Food and Drug Administration’s ability to protect the public from flawed medical devices.

The Axxent FlexiShield Mini had been cleared by the agency in June 2009 in an abbreviated process used for devices that are considered equivalent to products already on the market. That process, known as 510(k), takes less time than the procedure used to approve a new device, and it generally does not require tests on humans. The FlexiShield Mini equipment was recalled last month. Neither its manufacturer nor the F.D.A. could explain what went wrong with the device.

Karen Riley, a spokeswoman for the agency, said it was just beginning its review of the device and the recall. So far, she said, F.D.A. toxicologists had found no evidence that the tungsten was toxic or that patients were harmed.

Ms. Riley said the 510(k) process was used to avoid “reinventing the wheel” for products that were essentially the same as others that had already passed muster with the agency.

The women who were exposed to the tungsten were taking part in a study of a radiation technique that some doctors predicted would be a big advance in the treatment of breast cancer. Unlike the usual five to seven weeks of daily radiation sessions, the newer method delivers the entire course of treatment in one dose while the woman is still in the operating room after undergoing a lumpectomy for breast cancer.

But in the study, a device that was temporarily placed in the women’s incisions during the radiation treatment was apparently flawed, and riddled their breasts with tungsten. The Axxent Flexishield Mini, a $100 disk made of tungsten and silicone, was used to shield healthy tissue from the radiation.

The first patient to take part in the study at Hoag said the events had shattered her faith in the vigilance of the drug agency, the hospital and her surgeon, who she said enthusiastically talked her into participating, emphasizing how convenient it would be to finish radiation treatment before she even woke from surgery.

“I do work, so it was appealing,” said the woman, a 57-year-old psychologist with a busy practice who did not want her name used for privacy reasons.

The purpose of the study was not to test the new radiation treatment itself, but rather to determine whether imaging studies could correctly predict which women would be candidates for it. The device’s manufacturer did not pay for the study.

It never occurred to the first patient that the equipment might be faulty, she said, because she knew that it had been approved by the F.D.A. She also trusted the doctor and hospital to ensure that the study was safe.

“I had this illusion, like most people do, that the F.D.A. wouldn’t allow this to happen,” she said. “I definitely feel like a lab rat now.”

The manufacturer, Xoft, which was bought in December by iCad, intended the shield to be used with its portable radiation device, the Axxent Electronic Brachytherapy System.

The president of iCad, Ken Ferry, said his company bought Xoft because the idea of giving radiation treatment during surgery seemed so promising. A study published last summer showed good results from a different radiation machine using the same technique. Mr. Ferry said he thought the procedure might eventually be used to treat half of the 270,000 women a year in the United States who develop breast cancer.

“We think the growth of the procedure will be dramatic over the next three years,” Mr. Ferry said. “That’s what really drove us to acquire the company.”

But iCad also acquired the tungsten problem, which became apparent only a week or two after the deal was closed.

“Dumb luck, if you want to use that word, is what it feels like to iCad that we ran into it,” Mr. Ferry said. But, he added, “it doesn’t diminish our enthusiasm.”

The psychologist is suing Hoag and the manufacturer.

She first learned that something was wrong in December, when she had a routine follow-up mammogram six months after her lumpectomy and radiation.

The image showed hundreds of tiny spots scattered inside her breast and along the muscle at the back of her chest wall. Doctors did not know what the spots were, but her radiologist said some resembled the calcifications that can indicate cancer. “I was terrified,” she said. “It looked like it was snowing inside my breast.”

A biopsy found the tungsten.

“I went to my oncologist,” she said. “He just was beside himself. He just said: ‘You’ve got to get this out of you. It’s toxic. You can’t have this in your system.’ ”

He urged her to have a mastectomy and recommended a surgeon, who told her that to remove the tungsten, he would have to remove her entire breast and some of the chest muscles.

“I would have a dent in my side,” she said. “He said he didn’t really want to move ahead until there was more information because it would be so disfiguring. That made me physically ill. I’d kind of gotten myself used to the idea of having a mastectomy, but not being disfigured.”

ICad has offered to pay for toxicology consultations for the exposed women, along with blood and urine tests to measure tungsten. The company has also said it will consider paying for mastectomies, and it commissioned a report to examine the scientific data on tungsten. The report said its toxicity appeared low, but that long-term studies were lacking.

Dr. Steven Markowitz, a physician at Queens College in New York who specializes in occupational and environmental medicine, said there was not much information about the effects of pure tungsten like that used in the shields. Most research, he said, involves workplace exposure to tungsten compounds.
“Given this unorthodox route of exposure, it’s hard to say a whole lot about likely consequences,” Dr. Markowitz said.

The first patient in the Hoag study said she had consulted a toxicologist, who told her little was known about the long-term health effects of tungsten but said that she (the toxicologist) would probably not leave it in her own body. The patient said that she was leaning toward having the surgery. But, she added, “I would love to hear there’s evidence that there’s nothing to worry about.”

(AP) Researchers are making progress on a blood test that can spot a single cancer cell among a billion healthy ones.

The health care company Johnson & Johnson says it will join scientists at Massachusetts General Hospital, where the test was invented, to try to bring the test to market within the next several years.
Researchers think the test has the potential to transform care of many types of cancer, especially breast, colon, prostate and lung.
Doctors hope to use it to determine what treatment would be best for a particular tumor, and to find out quickly if the treatment is working.
Ultimately, the test may offer another way to screen for cancer besides the mammograms, colonoscopies and other methods used now. But that will require more study.

Vitamin D Levels Low Even In Breast Cancer Patients Taking Supplements
Zosia Chusteck/Medscape

December 10, 2010 (San Antonio, Texas) — Vitamin D levels are low even in postmenopausal women with breast cancer who are taking supplements, a new study has found.

The research was featured in a poster presentation here at the 33rd Annual San Antonio Breast Cancer Symposium. It was based on a cross-sectional study of 391 postmenopausal women with stage I to III breast cancer who were taking aromatase inhibitors. Vitamin D deficiency was found in 35% of these women.
A majority of the women (73%) were taking vitamin D supplements, but even among this group, vitamin D deficiency was found in 25%.

The main message from this work is that vitamin D supplementation is not "one size fits all," said lead author Claire Friedman, BS, from the New York University School of Medicine in New York City. There are some women who might benefit from extra doses, such as women who are obese and overweight or who are nonwhite, she told Medscape Medical News.

The finding that so many of these postmenopausal breast cancer survivors were found to be vitamin D deficient is of concern, because previous research has shown that vitamin D deficiency is associated with worse breast cancer outcome, she explained.

Ms Friedman is a fourth-year medical student, and was working under the guidance of senior author Jun Mao, MD, MSCE, from the University of Pennsylvania in Philadelphia. The patients were being treated at the Rena Rowan Breast Cancer Center at the University of Pennsylvania, she noted.
Vitamin D levels were measured in a blood sample taken from each patient, and deficiency was defined as a level below 30 ng/mL.

The median level of vitamin D was 35 ng/mL (range, 6.78 to 93.15).
However, 35% of women had levels of vitamin D that indicated deficiency. After adjustment for age and vitamin D supplementation, the researchers found that vitamin D deficiency was more likely to be found in minorities than in whites (adjusted odds ratio, 2.18; P = .009), and in women who were obese or overweight than in those of normal weight (adjusted odds ratio, 3.21; P < .001).
"Hypovitaminosis D is common in breast cancer survivors, and women who are nonwhite or overweight are at higher risk of deficiency, despite taking vitamin D supplements," the researchers conclude.

33rd Annual San Antonio Breast Cancer Symposium (SABCS). Abstract P2-14-11. Presented December 10, 2010.

High CTC levels predicted poor outcome in metastatic breast cancer
SAN ANTONIO — A high level of circulating tumor cells (CTCs) — cells that have detached from a tumor and are circulating in the body through the blood — are an independent prognostic marker in metastatic breast cancer as first-line therapy. In addition, persistence of high CTC level during therapy was found to be an early marker of poor outcome.

"This is the largest, prospective series validating the prognostic value of CTCs in first-line chemotherapy metastatic breast cancer, independently from serum tumor markers for overall survival," said Jean-Yves Pierga, M.D., Ph.D., professor of the medical oncology department, Institut Curie and Université Paris Descartes, France. "Persistence of a high level of CTCs before the second cycle of chemotherapy was a strong and early predictive marker of poor outcome."

Pierga presented results of this study at the 33rd Annual CTRC-AACR San Antonio Breast Cancer Symposium, held here Dec. 8-12, 2010.

Breast cancer can metastasize from a primary tumor in the breast to distant organs, such as the liver, lungs or bone, through the blood. New techniques have allowed for the detection of metastasis by testing blood for CTCs.
Previous research has not established that routine use of CTC measurements can improve patient outcomes, therefore, it is not currently a recommended practice, said Pierga.

The researchers prospectively tested CTCs as an outcome predictor compared with serum tumor markers in metastatic breast cancer patients treated by first-line chemotherapy. Serum tumor markers are proteins or glycoproteins released into the blood; however, tumor markers only indirectly reflect the presence of cancer and can be associated with dead cells, according to Pierga. In fact, some breast cancers can metastasize without any increase in tumor serum markers.

This study included 267 patients with metastatic breast cancer who were receiving first-line chemotherapy and had undergone assessment for three tumor markers: CA 15.3, CEA and LDH. Patients were enrolled in one of five cancer centers in France between June 2007 and Sept. 2009, and were followed for a median of 16 months.

Sixty-five percent of the patients had one or more CTCs; 44 percent had five or more CTCs. Of the measured tumor markers, 64 percent of patients had high CA 15.3, 51 percent had high CEA and 45 percent had high LDH.

High CTC levels were predictive of poor progression-free survival and overall survival, independent of serum tumor markers.

Evaluation of serum tumor markers showed that baseline levels of CA 15.3, CEA and LDH were prognostic for poor progression-free survival, but only LDH was prognostic for overall survival. CTCs were highly associated with tumor markers, tumor burden, performance status, and number of metastatic sites, but were also independent of tumor biology, such as HER2 status, or grade of cancer.

"CTCs add an independent prognostic marker in metastatic breast cancer at first-line chemotherapy, and an early predictive marker of clinical benefit after one cycle of chemotherapy," Pierga said.


Mixed Result for Bone Drug in Cancer Study
By Andrew Pollack, NY Times

The results of a new study are tempering hopes that a drug used to treat bone loss might also help stave off relapses of breast cancer especially for younger women, researchers said Thursday.

The clinical trial found that women with early breast cancer who were treated with the bone drug zoledronic acid did not have fewer recurrences of their cancer than women who did not receive the drug. The results surprised and disappointed some experts because they conflicted with the findings of a previous, widely publicized trial.

“Most people in the breast cancer community were very hopeful that this would be a positive study,” Dr. Sharon Giordano of the M. D. Anderson Cancer Center in Houston said in an interview. She was not involved in the study but is to deliver a commentary about it on Friday at the San Antonio Breast Cancer Symposium, where the results will be presented.

Still, Dr. Giordano and others said the latest results would not be the final word because additional studies were under way. Moreover, the new study suggested that the bone drug could help stave off recurrences for women well past menopause.

Zoledronic acid, sold by Novartis under the name Zometa, is one of a class of bone drugs known as bisphosphonates. It is approved to prevent fractures and other skeletal problems that can occur when breast cancer or other tumors spread to the bone.

A study published in The New England Journal of Medicine in February 2009 suggested that zoledronic acid would be useful in treating the cancer itself. In that trial, the bone drug reduced the risk of breast cancer recurrence or spread by about a third.

A leading theory for that effect was that the breakdown of bone provided substances that stimulate tumor growth. Drugs that slow that breakdown deprive tumors of those substances.

But the new study contradicts those findings. This study involved 3,360 patients, mainly in Britain, who had their breast tumors removed by surgery and underwent whatever chemotherapy or other treatment their physicians chose to prevent recurrence. Half the patients also received intravenous infusions of zoledronic acid for five years.

After nearly five years, the number of women who had had a recurrence or had died without a recurrence was about the same — 403 in the control group and 404 in the group receiving zoledronic acid. Those receiving the bone drug had a somewhat lower risk of dying, but the difference was not statistically significant.

However, the bone drug did seem to help women in the study who were at least five years past menopause, who accounted for about 30 percent of the participants. Among these women, there were 116 recurrences for those who got zoledronic acid compared with 147 in the control group, a risk reduction of 27 percent. Their risk of death was reduced 29 percent, with 86 deaths among those who got the drug compared with 120 deaths in the control group.
Dr. Robert E. Coleman of the University of Sheffield in England, the lead investigator of the study, said this suggested that zoledronic acid could help prevent relapse or spread only in the absence of estrogen or some other substance no longer produced by postmenopausal women.

In the study from nearly two years ago, the 1,800 participants were all premenopausal but were given a drug that shut down their ovaries, preventing them from making estrogen.

Dr. Michael Gnant of the Medical University of Vienna, who was the lead investigator of the earlier study, said at a news conference at the San Antonio symposium that the new results strengthened his belief in zoledronic acid.
But Dr. Giordano said that conclusions based on a subset of patients must be regarded with caution and that they should not change medical practice. She and others said there were other differences between the trials that might explain the divergent outcomes.

One thing experts agreed on was that zoledronic acid should now not be given to younger women with functioning ovaries unless the cancer had spread to their bones. That is true not only because the new trial showed no cancer benefit for these women but also because the drug can destroy jawbones in some patients.

The new study was sponsored by the University of Sheffield. Dr. Coleman and Dr. Gnant are paid consultants for Novartis, which contributed some money.
Just last week, a study published in The Lancet showed that zoledronic acid reduced the risk of disease progression and improved survival in patients with multiple myeloma, a cancer of the bone marrow.

Benefits of Estrogen Are Debated
By Tara Parker Pope/ NY Times

Certain women who take estrogen to relieve menopausal symptoms may be protected from Breast Cancer according to data released Thursday at the San Antonio Breast Cancer Symposium.

The finding, an analysis of data from a study known as the Women’s Health Initiative, drew criticism. Other studies have shown that hormone combinations that include estrogen and progestin increase breast cancer risk.
The new analysis involved women who had had Hystorectomies and as a result took only estrogen. The study, by Dr. Joseph Ragaz, an oncologist and clinical professor at the University of British Columbia, showed a statistically significant lower risk of breast cancer among estrogen users who did not have a family history of breast cancer.

The finding applies only to women who have had hysterectomies; a woman with a uterus who seeks Menopause treatment must use estrogen plus progestin to prevent uterine cancer.

Dr. Ragaz said he wanted to call attention to the health initiative data to reassure women and to encourage more study of the role estrogen alone may play.

“Estrogen alone for women who suffer menopause symptoms is actually safe and may be highly protective,” he said.

The report met with skepticism from other experts. Four years ago, the health initiative reported that women who used estrogen alone did not face higher breast cancer risk and might have a lower risk, said Dr. Rowan Chlebowski, a professor of medicine at the University of California, Los Angeles. “There is nothing new here,” he said.

Weightlifting Reduces Likelihood of Lymphoedema After Breast-Cancer Treatment: Presented at SABCS

    •    By Jill Stein SAN ANTONIO -- December 9, 2010 -- Weightlifting can significantly decrease the risk of lymphoedema after treatment for breast cancer, according to data presented here at the 33rd annual San Antonio Breast Cancer Symposium (SABCS). Kathryn Schmitz, PhD, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, said results of her team's study undermine the popular notion that breast-cancer survivors with lymphoedema or at risk of lymphoedema should categorically avoid upper-body exercise.

The recommendation against upper-body exercise in these patients has been described in clinical guidelines. About 47% of women who undergo surgery to remove multiple lymph nodes near the breast typically develop lymphoedema, Dr. Schmitz said on December 8. Her team randomised 295 breast-cancer survivors with stable arm lymphoedema or survivors at risk of lymphoedema to either a treatment group involving 13 weeks of supervised instruction followed by 9 weeks of no instruction or to a control group that only received the intervention after study completion.

During the 13-week instruction period, women attended twice-weekly, 90-minute classes led by certified fitness professionals who taught them techniques for upper- and lower-body weightlifting using both free weights and machines. The primary outcome was the change in arm swelling at 1 year, as measured by water volumetry of the affected and unaffected arms.

Results showed that the weightlifting regimen decreased the risk of lymphoedema by 35%; that is, 11% of women in the weightlifting treatment group developed lymphoedema versus 17% of women in the control group, who did not alter their normal physical-activity regimen. The analysis also showed that the weightlifting intervention had a more dramatic impact in the subset of women with >=5 lymph nodes excised during surgery. This subgroup had a nearly 70% risk reduction, with 22% of control patients developing lymphoedema, compared with 7% in the treatment group.

Dr. Schmitz emphasised that women with lymphoedema or at risk of the condition should speak with their physician before embarking on a weightlifting program. [Presentation title: Balancing Risk for Deconditioning vs Weight-Lifting for Breast Cancer Survivors. Abstract ES9-3]

Syndax Pharmaceuticals' Entinostat in Combination Shows Activity in Breast Cancer

--Animal data being presented at the San Antonio Breast Cancer Symposium--

WALTHAM, Mass., Dec. 10, 2010 /PRNewswire/ -- Syndax Pharmaceuticals, Inc., a clinical-stage epigenetics oncology company, announces results from two preclinical studies on entinostat, an orally bioavailable, highly selective, class I histone deacetylase (HDAC) inhibitor, in animal models of breast cancer. The data are being presented as oral poster discussions at the San Antonio Breast Cancer Symposium December 8 through December 12 in San Antonio Texas.

The following poster discussions are being presented:
    •    "A Combination of HDAC Inhibitor Entinostat (MS-275), All Trans Retinoic Acid (ATRA) and Chemotherapy Drug(s) Causes Regression of Established Xenografts of Triple Negative Breast Cancer" December 9, 2010 from 5:30 to 7:30 PM CT by Nguyen K. Nguyen from Johns Hopkins University School of Medicine

    •    "HDAC Inhibitor Entinostat Restores Responsiveness of Letrozole Resistant MCF-7Ca Xenografts to AIs through Modulation of Her-2" December 10, 2010 from 5:30 to 7:30 PM CT by Gauri J. Sabnis, Ph.D. from the University of Maryland School of Medicine

"These promising results in predictive animal models provide important insight into the molecular mechanisms by which entinostat can target resistance pathways in breast cancer," said Joanna Horobin, M.D., president and chief executive officer of Syndax. "In the phase 2 ENCORE 303 study presented at ASCO, we showed that the addition of entinostat could halt disease progression emerging on treatment with all of the commercially available aromatase inhibitors. Dr. Sabnis' work provides an elegant hypothesis supporting our clinical findings. We are optimistic that our ongoing ENCORE 301 study, a double-blind, randomized, placebo-controlled phase 2 study of entinostat in combination with the aromatase inhibitor exemestane, will provide further evidence supporting the clinical benefit and tolerability of entinostat in postmenopausal women with progressing metastatic breast cancer. We expect to see results in the first half of next year."

The University of Maryland study looked at the ability of entinostat to restore responsiveness of letrozole resistant MCF-7Ca xenografts to aromatase inhibitors. Entinostat was able to increase estrogen receptor expression and aromatase activity in the letrozole resistant tumors. The results suggest that entinostat may modulate Her-2 signaling and reverse the acquired resistance to letrozole caused by up-regulation of estrogen independent growth factor signaling pathways.

"While aromatase inhibitors have significantly improved the outcomes of hormone responsive post-menopausal breast cancer, not all tumors respond and many eventually acquire resistance," said Gauri J. Sabnis, Ph.D., assistant professor of pharmacology and experimental therapeutics at the University of Maryland School of Medicine. "These animal models have been confirmed in the clinic giving us hope that entinostat, if approved, will provide these women with a new treatment option to help overcome the resistance that many of them experience while on aromatase inhibitors."

Triple negative breast cancer (TNBC) is a sub-group of breast cancer that is normally unresponsive to hormone therapy as well as many forms of chemotherapy. Researchers from Johns Hopkins University School of Medicine reasoned that combining epigenetic therapy, entinostat, with differentiation therapy, retinoic acid receptor beta 2 agonist (ATRA) will provide an effective combination of drugs against TNBC. Low-doses of chemotherapy also were added to the combination. The results showed that entinostat plus ATRA and doxorubicin has the potential to be an effective treatment against TNBC.

"These findings provide encouraging new information for a non-toxic and novel combination of drugs with entinostat that could be effective in the treatment of triple negative breast cancer -- a condition desperately in need of new treatments," said Sara Sukumar, Ph.D., professor of oncology and pathology at Johns Hopkins University School of Medicine. "With chemotherapy as the primary treatment option for triple negative breast cancer patients, these results are encouraging that this patient population could have another treatment option in the future."

For more Information regarding the SABCS presentations please visit the SABCS website at

About Entinostat
Entinostat is an orally bioavailable, highly selective, class I histone deacetylase (HDAC) inhibitor with a long half-life that allows for weekly or every-other-week dosing. Entinostat is currently being investigated in multiple phase 2 clinical studies: in advanced breast cancer in combination with aromatase inhibitors; in combination with erlotinib in metastatic lung cancer and as a single agent in Hodgkin's lymphoma. Entinostat also is being studied in advanced non-small-cell lung cancer and in advanced colorectal cancer in combination with azacitidine under a Cooperative Research and Development Agreement (CRADA) with the NCI.

Research has shown that HDACs are involved in the expression of various genes, such as the estrogen receptor, that regulate cell growth, differentiation and apoptosis. Such genes are frequently silenced in cancer cells through the over-expression of enzymes including HDACs. HDACs are therefore recognized as promising targets for cancer treatment. Further, studies have demonstrated that HDAC inhibition can significantly enhance anti-cancer activity when used in combination with a broad range of anti-cancer agents. The potential therefore exists to overcome tumor resistance to targeted agents.

SOURCE Syndax Pharmaceuticals, Inc.

Muscle and Joint Symptoms are Common During Taxane-based Treatment for Breast Cancer: Presented at SABCS

    •    By Jill Stein SAN ANTONIO -- December 10, 2010 -- New data show a high frequency of muscle and joint symptoms during taxane treatment for breast cancer. The findings were released on December 10 here at the 33rd annual San Antonio Breast Cancer Symposium (SABCS). Jenna van Draanen, Odette Cancer Centre, Toronto, Ontario, and colleagues presented results from 95 women receiving taxane-based therapy for breast cancer. The prevalence and severity of muscle and joint symptoms in patients receiving taxane-based chemotherapy are poorly documented, according to the authors. They added that oestrogen may play a role in inflammation and nociceptive neural processing, and chemotherapy-induced premature menopause may influence muscle and joint symptoms. At baseline, all women were taxane-naïve and were scheduled to receive at least 3 cycles of docetaxel, paclitaxel, or nab-paclitaxel chemotherapy.

All of them completed questionnaires and symptom diaries every 3 months for 12 months following each cycle. Results showed that the percent of patients reporting joint pain peaked at 67.9%, 66.1%, and 59.4% in cycles 1, 2, and 3, respectively. The mean worst joint pain score remained high in all cycles with pain scores peaking on day 5 at 6.0 on a 10-point scale, 5.1, and 5.2 for cycles 1, 2, and 3, respectively. The proportion of patients experiencing muscle pain peaked at 63.8%, 60.9%, and 61.9% in cycles 1, 2, and 3, respectively. Throughout the 3 cycles, the mean worst muscle pain score remained high with pain scores peaking on day 5 at 5.7, 4.9, and 4.9 for cycles 1, 2, and 3, respectively. More than a third of patients reported that their muscle and joint symptoms interfered with an activity of daily living. Overall, this study confirms the significant burden of muscle and joint symptoms during taxane chemotherapy, the authors said. They emphasised, however, that the methodology used in the study only allowed for descriptive analysis and did not allow the attribution of pain to chemotherapy.

[Presentation title: Muscle and Joint Symptoms in Breast Cancer Patients Receiving Taxane-Based Chemotherapy. Abstract P3-15-05]

ImmunoGen, Inc. Announces Clinical Data for T-DM1 Used in Combination with Pertuzumab for First-Line Treatment of HER2+ Metastatic Breast Cancer

WALTHAM, Mass.--(BUSINESS WIRE)--ImmunoGen, Inc. (Nasdaq: IMGN), a biopharmaceutical company that develops anticancer therapeutics using its Targeted Antibody Payload (TAP) technology, today announced the presentation of the first clinical data for trastuzumab-DM1 (T-DM1) used in combination with pertuzumab for first-line treatment of HER2+ metastatic breast cancer (mBC). These data were presented at the 33rd Annual San Antonio Breast Cancer Symposium (SABCS).

“The data that have been reported with T-DM1 for the first-line treatment of HER2+ metastatic breast cancer are highly encouraging, both with T-DM1 as a single agent and used in combination with pertuzumab”
T-DM1 consists of the HER2-targeting antibody, trastuzumab, with ImmunoGen’s cancer cell-killing agent attached using the Company’s linker and method of attachment. T-DM1 is in global development by Roche under a licensing agreement between ImmunoGen and Genentech, a member of the Roche Group. Pertuzumab is a HER2 Dimerization Inhibitor in development by Roche.

T-DM1 Plus Pertuzumab for First-Line HER2+ mBC
The data reported today are from a Phase Ib/II clinical trial conducted by Roche to assess T-DM1 used in combination with pertuzumab to treat HER2+ mBC. The study enrolled 21 patients who had not received prior systemic anticancer therapy for metastatic disease. Among these patients, 57.1% had a confirmed objective response to treatment with T-DM1 plus pertuzumab.
All of these patients had received anticancer agents prior to their development of metastatic disease (e.g., as adjuvant therapy). Eighty-six percent (86%) of these patients had received Herceptin® (trastuzumab), 71% had received a taxane, and 62% had received an anthracycline before being diagnosed with metastatic disease.

T-DM1 Used Alone for First-Line HER2+ mBC
In October, preliminary data were reported for T-DM1 used alone as first-line treatment for HER2+ mBC.1 Those data were from a 137-patient, randomized Phase II trial. At the time of the cut-off date for the data included in that presentation, 47.8% of patients receiving T-DM1 as a single agent had a confirmed objective response, as compared to 41.4% of patients treated with Herceptin used in combination with a taxane. It was noted in the oral presentation that the study groups included patients with unconfirmed responses at the time of the data cut-off. Updated data from this trial are expected in 2Q2011.

“The data that have been reported with T-DM1 for the first-line treatment of HER2+ metastatic breast cancer are highly encouraging, both with T-DM1 as a single agent and used in combination with pertuzumab,” commented Daniel Junius, President and Chief Executive Officer. “Our TAP technology is designed to produce effective anticancer agents that also are well tolerated, supporting their evaluation in earlier stages of disease and/or as part of combination regimens.”

About the Development of T-DM1 for First-Line Use
In addition to the Phase II trial reported, a Phase III trial, MARIANNE, is underway that assesses T-DM1 for first-line treatment of HER2+ mBC. In MARIANNE, T-DM1 given as a single agent and T-DM1 given in combination with pertuzumab are both compared to Herceptin used in combination with a taxane.

About the Trial Reported at SABCS
The Ph 1b/II trial reported at SABCS was designed to assess T-DM1 used in combination with pertuzumab for HER2+ mBC, both as first-line therapy and to treat patients with disease that had recurred after treatment with other anticancer regimens. In addition to the findings reported at SABCS for the first-line setting, data were reported for the 46 patients with relapsed disease which were consistent with those previously reported for a subset of these patients.2

About ImmunoGen’s Targeted Antibody Payload (TAP) Technology
The Company’s TAP technology uses tumor-targeting manufactured antibodies to deliver one of ImmunoGen’s highly potent cancer-cell killing agents (e.g., DM1, DM4) specifically to tumors. These agents are many-fold more potent than standard chemotherapy drugs and were developed by ImmunoGen specifically for targeted delivery to tumors. ImmunoGen also has engineered linker technology that keeps the cancer-cell killing agent attached to the antibody until it reaches the cancer cell and then controls the release of the agent inside the cell. In addition to T-DM1, six other compounds that make use of ImmunoGen’s TAP technology are in clinical testing.

About ImmunoGen, Inc.
ImmunoGen, Inc. develops targeted anticancer therapeutics using the Company's expertise in tumor biology, monoclonal antibodies and potent cancer-cell killing agents. The Company's TAP technology uses monoclonal antibodies to deliver one of ImmunoGen's proprietary cancer-cell killing agents specifically to tumor cells. There are currently seven TAP compounds in the clinic, with a wealth of clinical data reported with the technology. ImmunoGen’s collaborative partners include Amgen, Bayer Schering Pharma, Biogen Idec, Biotest, Genentech (a member of the Roche Group), Novartis, and sanofi-aventis. The most advanced compound using ImmunoGen's TAP technology, trastuzumab-DM1 (T-DM1), is in Phase III testing through the Company's collaboration with Genentech. More information about ImmunoGen can be found at
1Perez, E., Dirix, L., Gianni, L., et al. ESMO 2010. 2Miller, K., Gianni, L., Andre, F, et al. ASCO 2010.
Herceptin® is a registered trademark of Genentech.

Pfizer, Novartis, AstraZeneca Cancer Drugs Raise Heart Risks, Study Says
By Michelle Fay Cortez - Dec 9, 2010 10:15 AM ET Thu Dec 09 15:15:25 GMT 2010

Pfizer Inc.’s breast-cancer drug Aromasin and similar treatments from AstraZeneca Plc and Novartis AG make women 26 percent more likely to develop heart disease than an older therapy, a study found.

The trial, presented today at the San Antonio Breast Cancer Symposium in Texas, suggests that women already at risk for cardiac conditions should limit use of these drugs, researchers said. Tamoxifen, a generic alternative approved in 1977, carries less risk of heart complications, the study found.

Aromasin, AstraZeneca’s Arimidex, and Femara from Novartis, are in a family of medicines known as aromatase inhibitors that work by halting production of estrogen, a hormone that fuels cancer growth. These drugs generated more than $3.5 billion last year, often used after tamoxifen, which prevents tumor cells from using estrogen. Two thirds of all breast-cancers are fed by estrogen, according to the National Institutes of Health.

“It appears that aromatase inhibitors have a significant increase in cardiotoxic side effects, such as heart attack, angina and heart failure,” said Eitan Amir, a senior fellow in oncology and hematology at the Princess Margaret Hospital in Toronto, in a statement. “Switching drugs may reduce the side effects.”
Heart disease is the leading cause of death in women, killing almost 433,000 annually, according to the American Heart Association. An estimated 209,000 women will be diagnosed with breast cancer this year, making it the most common tumor type in women, according to the American Cancer Society. More than 40,000 women die from it each year.

Heart, Fracture Risk
Women who took aromatase inhibitors were 26 percent more likely to have heart disease and 47 percent more likely to suffer a fracture than those on tamoxifen, regardless of how long they took the medicine, an analysis of seven studies used to win approval of the drugs found. The research was conducted in older, post-menopausal women with early breast cancer. Patients on tamoxifen were more likely to develop endometrial cancer and dangerous blood clots in the legs during the studies. There was a suggestion that women who switched to aromatase inhibitors after starting on tamoxifen were less likely to die from something other than breast cancer than those who started treatment with the medicines. The approach didn’t seem to reduce the risk of serious side effects, the researchers said.

Drug Sales
Pfizer, based in New York, reported revenue of $483 million from Aromasin last year. London-based AstraZeneca had sales of $1.92 billion for Arimidex. Novartis, of Basel, Switzerland, generated $1.27 billion from Femara in 2009.
A second study today found Pfizer’s Aromasin worked as well as AstraZeneca’s Arimidex, the market leader with $1.9 billion in sales last year. The researchers originally hypothesized that Aromasin, currently used a second-line therapy, may be more effective with fewer side effects than Arimidex. They conducted the first head-to-head comparison of the medicines to identify any differences.

More than 7,500 women participated in the study, which was funded by the National Cancer Institute in the U.S. and the International Breast Cancer Study Group in Europe. Women taking Aromasin were less likely to have osteoporosis and elevated cholesterol levels, and had higher rates of mood changes and signs of reduced liver function.
To contact the reporter on this story: Michelle Fay Cortez in Minneapolis at

Roche's Avastin Fails to Beat Chemotherapy in Early Breast-Cancer Patients
By Michelle Fay Cortez and Dermot Doherty - Dec 10, 2010 7:53 PM ET Sat Dec 11 00:53:09 GMT 2010

Roche Holding AG’s Avastin failed to eradicate tumor cells better than standard chemotherapy in women with early stage breast cancer, a finding that could limit the efforts to expand use of the oncology drug.

The 1,190-patient trial found 15 percent of women on chemotherapy had no signs of disease when they underwent surgery, compared with 17.5 percent of those also given Avastin. The difference wasn’t statistically meaningful, researchers said yesterday at the San Antonio Breast Cancer Symposium.

The U.S. Food and Drug Administration is due to decide by Dec. 17 whether to revoke Avastin’s marketing clearance for breast malignancies. Outside advisers in July voted to rescind an accelerated approval after Avastin failed to show as much of a benefit when added to chemotherapy as hoped. The agency will rule on Avastin’s use with various chemotherapies. Results from four more Avastin trials in early breast cancer are pending.

“We’re still waiting for the results of the definitive trials, but it’s a little concerning,” said Eric Winer, chief of the division of women’s cancer at the Dana-Farber Cancer Institute in Boston. “I don’t think people are thinking necessarily so positively.”

The goal of the trial was to wipe out even microscopic signs of disease in an effort to cure more women. The study, funded by Roche, of Basel, Switzerland, and Paris-based Sanofi- Aventis SA, provides the first results from late-stage testing of Avastin in women with early breast cancer, according to Gunter von Minckwitz, managing director of the German Breast Group, which ran the study.

$6.3 Billion Revenue
Avastin generated 6.2 billion Swiss francs ($6.3 billion) in revenue last year. The medicine was developed by Roche’s South San Francisco, California-based Genentech unit, fully acquired by the European drugmaker last year for $46.8 billion.

The drug is approved in several other cancer types, including colorectal, lung and brain tumors. Avastin is the first medicine to fight cancer by blocking the growth of blood vessels that feed tumors, a process called angiogenesis. Roche has said it expected U.S. sales of Avastin in breast cancer to be about $600 million this year.

There are more studies under way with the use of Avastin in early breast cancer after surgery, said Sandra Horning, global head of clinical development hematology and oncology at Roche’s Genentech unit. Little is known about how Avastin will work when it is given before surgery, known as the neoadjuvant setting, where the company has one study, she said.
“We felt that it was important, given the results we’ve seen in the advanced stage, to study it in the early stage as well,” Horning said in an interview. “There is more information coming. We still have a lot to learn.”

Previous Studies
Two previous studies of Avastin as a treatment for early- stage colorectal cancer also failed to meet their main goals. Roche is seeking to boost sales of the drug by testing it in more tumor types and in earlier stages of the disease.
European regulators said Sept. 24 they would review Avastin’s use in metastatic breast tumors. A clinical trial that Roche says supports expanded use of the treatment was inconsistent with results from previous studies, particularly in terms of efficacy, according to the European Medicines Agency.
The FDA’s 2008 clearance overruled an advisory panel that concluded the benefit of slowing the spread of breast tumors wasn’t worth the risk of side effects including high blood pressure and death. Approval was accelerated, and done on the condition that later research confirmed Avastin’s benefit for breast cancer patients.

Decision Delayed
The FDA in September delayed its decision on whether to allow wider use of Avastin in breast cancer or rescind clearance for this use. The agency is set to decide by Dec. 17. The FDA usually follows panels’ advice, though it isn’t required.

Previous studies showed Avastin slowed the disease, said Edith Perez, deputy director of the Mayo Clinic Comprehensive Cancer Center in Jacksonville, Florida.

“For my patients, I think it’s good if we can delay progression,” she said in an interview. “I like to be able to tell a woman she will have a statistically significant better chance of being alive without cancer at one year.”

Important Information for Tamoxifen Users
We have been pushing for this test for a long time. Now it appears it has gained some attention.
This was sent to us by Coyne PR

Contact Information:
Bill Borden McDavid Stilwell Coyne PR GTx, Inc. 973-316-1665 901-507-2667

New Survey of Breast Cancer Patients Shows that Women Taking Tamoxifen Want a CYP2D6 Genetic Test

MEMPHIS, TN – December 6, 2010 – While the medical community continues to debate the benefits of CYP2D6 genetic testing for women on the breast cancer treatment tamoxifen, patients using the medication are anxious to have the tests. According to a new survey of more than 700 women with breast cancer currently taking tamoxifen, almost 80 percent of respondents would choose to have a genetic test that determines CYP2D6 genotype, yet only 14 percent of these women have been tested. CYP2D6 is an enzyme that influences how well the body processes tamoxifen into its more active form.

Several studies suggest that women determined to be “poor” or “intermediate” metabolizers of tamoxifen due to a CYP2D6 genetic variation may experience a higher cancer recurrence rate than those found to be “normal” metabolizers. Other studies, however, have not established a connection between CYP2D6 genetic variation and tamoxifen treatment outcomes. New research on the topic will be presented at the upcoming San Antonio Breast Cancer Symposium on December 9th.

“As a clinician, these data tell me that our patients want more discussion on the pros and cons of emerging science, in this case CYP2D6 testing, even if we don’t yet have definitive answers to all of their questions,” said Dr. William J. Irvin Jr. of the University of North Carolina, Chapel Hill, an oncologist and expert on CYP2D6 metabolism who also helped design the survey.

The survey also found that more than two-thirds of respondents (68 percent) were unaware that commonly used over-the-counter (OTC) medications (including sleep aids and allergy medicines containing diphenhydramine or acid reducers containing cimetidine) may interfere with the metabolism of tamoxifen. Twenty percent responded that they take OTC sleep aids or stomach acid reducers two to seven times each week.

Further, the majority of respondents (58.5 percent) were aware that commonly used antidepressants – such as fluoxetine, bupropion, sertraline and paroxetine – may interfere with the body’s ability to process tamoxifen. The most commonly used anti-depressant by respondents is venlafaxine which does not interfere with tamoxifen metabolism.

“It is encouraging to see the high level of patient awareness of antidepressant drug interactions with tamoxifen,” Dr. Irvin said. “This reflects the change in the practice of medicine over the last five years as it has become more broadly understood that certain medicines inhibit CYP2D6 metabolism.”

Survey Methodology
The survey, the first to explore patient awareness and attitudes regarding CYP2D6 metabolism and tamoxifen, was fielded over a three-week period in November 2010 among 791 women diagnosed with breast cancer who are currently taking tamoxifen. It was administered exclusively on, a leading online breast cancer information resource. The survey was sponsored by GTx, a pharmaceutical company which markets FARESTON 60mg (toremifene citrate) tablets, which is approved by the United States Food and Drug Administration for the treatment of metastatic breast cancer in postmenopausal women with estrogen receptor-positive (ER+) or unknown tumors.

Understanding the CYP2D6 – Tamoxifen Connection
Scientific researchers continue to explore how genetic differences and drug-drug interactions influence the body’s ability to metabolize certain medications. For example, for tamoxifen to work properly in the body, it must first be metabolized in the liver by CYP2D6 into a more active form called endoxifen.

It is estimated that as many as 30 percent of Caucasians and 50 percent of both African Americans and Asians may a genetic variation resulting in reduced activity of CYP2D6 and are “poor” or “intermediate” CYP2D6 metabolizers. These patients may not receive the same benefit from tamoxifen therapy as women with fully functional CYP2D6 activity. Additionally, several commonly used prescription antidepressants and OTC products such as sleep aids and allergy medicines are known to block the CYP2D6 enzyme, making it difficult for the body to process drugs such as tamoxifen. A more extensive list of medicines which may interfere with tamoxifen has been compiled by the Consortium on Breast Cancer Pharmacogenomics and can be found at

To date, studies on the correlation between CYP2D6, tamoxifen metabolism and recurrence rates have been mixed. A 2008 Mayo Clinic study showed that women with breast cancer taking tamoxifen who have an inherited deficiency in CYP2D6 enzymatic function have a nearly fourfold higher risk of early breast cancer recurrence than women who do not have the genetic deficiency.

Several other studies have shown women treated with antidepressants which inhibit tamoxifen metabolism to a similar degree as “poor” genetic metabolizers have a higher cancer recurrence rate than women not treated with these antidepressants. However, other recent studies have not shown a difference in cancer recurrence in women taking tamoxifen based on CYP2D6 status or the concomitant use of tamoxifen and commonly prescribed antidepressants. Regardless, experts agree that women taking tamoxifen should avoid certain antidepressants and OTCs; however few recommend that women receive the CYP2D6 test.

Important Safety Information about FARESTON
FARESTON is not right for everyone. Before taking FARESTON tell your doctor about any other medications that you are taking and if you are allergic to FARESTON or any of its ingredients. If you are pregnant, nursing or may become pregnant, do not take FARESTON, as it may cause fetal harm. Side effects may include hot flashes, sweating, nausea, vaginal discharge, dizziness and swelling. 
You should not take FARESTON if you have had or are at risk for getting blood clots in the legs, lungs or eyes, as it may increase the risk of blood clots. If you have leg pain or warmth, swelling of the legs, hands or feet, chest pain, shortness of breath or a sudden vision change, stop taking FARESTON and call your doctor as these may be signs of a blood clot. 

FARESTON may prolong a part of the heart rhythm known as the QT interval. Tell your doctor if you or a family member have had problems with heart rhythm or heartbeat (such as QTc prolongation) or if you are receiving drugs that prolong the QTc interval such as quinidine, dofetilide, sotalol, amiodarone, erythromycin, and certain antipsychotics. Before taking FARESTON talk to your doctor about all of your medical conditions.

You are encouraged to report negative side effects of prescription drugs to the FDA.  Visit or call 1-800-FDA-1088.

About GTx

GTx, Inc., headquartered in Memphis, Tenn., is a biopharmaceutical company dedicated to the discovery, development, and commercialization of small molecules that selectively target hormone pathways for the treatment and prevention of cancer, the treatment of side effects of anticancer therapy, cancer supportive care, and other serious medical conditions.


The D-bate on Vitamin D
A new study is out...this study replaces the old study that was once new but is now outdated because this one says so. Are you with me so far? Good.

I am a woman who has had breast cancer twice. When I got my E-Ticket to Cancerland the second time, my oncologist tested my Vitamin D blood level. I was severely deficient. He told me that most women who are diagnosed with breast cancer are. So we supplemented with a mega-dose once a week for a month and got it up a few points. Not enough, but we were headed in the right direction. At the same time he started me on Femara, a drug that is used to help women who have breast cancer that responds to estrogen, stay cancer-free. By inhibiting estrogen in the body, the buffet is closed to any hungry, opportunistic lurking cancer cells. Femara and drugs like it are saving women's lives. But it comes with a cost. Many women, one out of three to be exact, get horrible side effects from these drugs which include body aches, weight gain, and a general sense of misery. Add that to the lingering side effects of chemotherapy and it is hard to feel good again.

I believe there is a notation in my medical chart somewhere that reads: "Warning, this chick gets every side effect listed and even ones that aren't listed. She's even allergic to Benadryl." Now I ask you, who the heck is allergic to Benadryl??? Me.

I was ready for the onslaught of misery after breast cancer. I knew that little yellow pill that would keep the cancer away was going to do me in. It had to. Guess what? It didn't. I felt fine. No, better than fine. All the lingering chemo side effects went away, too. Was I finally catching a break? No. My vitamin D blood levels were above 50. Other studies have found that high blood values of D not only prevent breast cancer recurrence, but help prevent side effects from hormonal treatments for breast cancer. It also helps with body aches, mood swings and weight gain. I was the poster child for this theory.

I am not a doctor. I will not give you medical advice. But I will tell you this: the study I am attaching below is not going to effect my D taking routine. Because I know what it does for me. And I also know in a few months another study will come out contradicting it. If you want to be safe, don't take more than 2,000 ius a day. Get your D-level checked. If you are deficient, get it up there. Your body will thank you.

So with that preamble, please enjoy the latest new study on the Sunshine Vitamin :)
Report: A bit more vitamin D is good, not too much
November 30, 2010 by THE ASSOCIATED PRESS
WASHINGTON (AP) — Got milk? You may need a couple cups more than today’s food labels say to get enough vitamin D for strong bones. But don’t go overboard: Long-awaited new dietary guidelines say there’s no proof that megadoses prevent cancer or other ailments — sure to frustrate backers of the so-called sunshine vitamin.

The decision by the prestigious Institute of Medicine, the health arm of the National Academy of Sciences, could put some brakes on the nation’s vitamin D craze, warning that super-high levels could be risky.

“More is not necessarily better,” cautioned Dr. Joann Manson of Harvard Medical School, who co-authored the Institute of Medicine’s report being released Tuesday.

Most people in the U.S. and Canada — from age 1 to age 70 — need to consume no more than 600 international units of vitamin D a day to maintain health, the report found. People in their 70s and older need as much as 800 IUs. The report set those levels as the “recommended dietary allowance” for vitamin D.

That’s a bit higher than the target of 400 IUs set by today’s government-mandated food labels, and higher than 1997 recommendations by the Institute of Medicine that ranged from 200 to 600 IUs, depending on age.

But it’s far below the 2,000 IUs a day that some scientists recommend, pointing to studies that suggest people with low levels of vitamin D are at increased risk of certain cancers or heart disease.

“This is a stunning disappointment,” said Dr. Cedric Garland of the University of California, San Diego, who wasn’t part of the institute’s study and says the risk of colon cancer in particular could be slashed if people consumed enough vitamin D.

“Have they gone far enough? In my opinion probably not, but it’s a step in the right direction,” added prominent vitamin D researcher Dr. Michael Holick of Boston University Medical Center, who said the new levels draw needed attention to the vitamin D debate and encourage more food fortification.
Vitamin D and calcium go hand in hand, and you need a lifetime of both to build and maintain strong bones. But the two-year study by the Institute of Medicine’s panel of experts concluded research into vitamin’s D possible roles in other diseases is conflicting. Some studies show no effect, or even signs of harm.

A National Cancer Institute study last summer was the latest to report no cancer protection from vitamin D and the possibility of an increased risk of pancreatic cancer in people with the very highest D levels. Super-high doses — above 10,000 IUs a day — are known to cause kidney damage, and Tuesday’s report sets 4,000 IUs as an upper daily limit — but not the amount people should strive for.
And Manson pointed to history’s cautionary tales: A list of other supplements — vitamins C and E and beta carotene — plus menopause hormone pills that once were believed to prevent cancer or heart disease didn’t pan out, and sometimes caused harm, when put to rigorous testing.

Stay tuned: To help settle the issue, Manson is heading a government-funded study that’s recruiting 20,000 healthy older Americans to test whether taking 2,000 IUs of vitamin D really will lower their risk for heart disease, a stroke or certain cancers.

In the meantime, it’s hard to consume 600 IUs of vitamin D from food alone. A cup of D-fortified milk or orange juice has about 100 IUs. The best sources may be fatty fish — some servings of salmon can provide about a day’s supply. Other good sources are D-fortified cereals.

But here’s the report’s big surprise: While some people truly are seriously deficient in vitamin D, the average American in fact already has enough circulating in his or her blood — because we also make vitamin D from sun exposure, and because many people already take multivitamins or other D-containing dietary supplements.
Wait a minute: Headlines in recent years have insisted the opposite, that a majority of people don’t get enough vitamin D, especially during the winter. What explains the contradiction?

Most testing laboratories are using a too-high cutoff for those blood levels, said report co-author Dr. Clifford Rosen of the Maine Medical Center. The report says at least 20 nanograms is adequate for bone health, while many labs instead list people as low if their blood levels are below 30 ng. Serious vitamin D deficiencies are diagnosed when levels dip well below 20, something that hasn’t changed.
Rosen called the state of vitamin D testing “the wild, wild West,” and said he hoped that “with this report, we can at least temper people’s enthusiasm for just taking tons of supplements.”

As for calcium, the report recommended already accepted levels to go along with your daily D
— about 1,000 milligrams of calcium a day for most adults, 700 to 1,000 mg for young children, and 1,300 mg for teenagers and menopausal women. Too much can cause kidney stones; the report said that risk increases once people pass 2,000 mg a day.

It’s true that most studies link poor health to vitamin D levels that are below 20 ng, said preventive cardiologist Dr. Erin Michos, a Johns Hopkins University School of Medicine professor who wasn’t part of the study.

But, “I’m not sure I’m going to dramatically change my practice,” said Michos, who pushes her patients to boost their levels until they’re between 30 and 50 ng.
Xgeva Approved to Prevent Fractures in Bone Cancer Patients
Fri Nov 19, 11:47 pm ET

FRIDAY, Nov. 19 (HealthDay News) -- Xgeva (denosumab) has been approved by the U.S. Food and Drug Administration to prevent fractures and other skeletal complications in people with advanced cancer that has metastasized (spread) to the bones.
As many as 75 percent of people with advanced cancer of the prostate, lung or breast have it spread to the bones, Xgeva's manufacturer, Amgen Inc., said in a news release. This may lead to complications such as debilitating pain, bone fractures and compression of the spinal cord, the drug maker said.
Xgeva, injected once monthly, targets a cancer-related protein that destroys bone cells, the FDA said in a news release. The drug's safety and effectiveness were evaluated in clinical studies involving 5,723 people. The trials showed Xgeva was superior to, or at least as effective, as an older drug designed to reduce bone complications from cancer, Zometa (zoledronic acid).
Side effects of Xgeva included lower blood calcium levels, and osteonecrosis of the jaw, a severe disease resulting from reduced blood flow to the jaw, the FDA said.
In June, the drug was first approved under a different name, Prolia, to treat postmenopausal women at high risk of osteoporotic bone fractures.
Amgen is based in Thousand Oaks, Calif.

Cough Syrup Might Help With Dosing of Breast Cancer Drug
Fri Nov 19, 11:47 pm ET

FRIDAY, Nov. 19 (HealthDay News) -- A new, small study suggests that the main ingredient in cough syrup might help doctors determine the best dose of tamoxifen, a drug commonly used to prevent and treat breast cancer.
The idea is that the body absorbs cough medicine at about the same rate as tamoxifen, allowing doctors to use it to test how patients respond to the breast-cancer drug.
"This study is starting to identify a personalized medicine type of approach that will help identify those patients who should have their tamoxifen doses adjusted," said Dr. Leonidas Koniaris, who's familiar with the study findings. He's an associate professor of surgery at the Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine in Florida.
Currently, it can be difficult to set a proper dose of tamoxifen for a patient. If the dose is off, the drug may lose effectiveness or cause a higher number of side effects, the study authors said.
The authors, led by Anne-Joy de Graan, a graduate student at Erasmus Medical Center in Rotterdam, the Netherlands, focused on whether dextromethorphan, the active ingredient in cough medicine, is metabolized by the body at about the same rate as tamoxifen. Dextromethorphan "is a so-called 'probe' drug, a harmless substance that can be used to predict the metabolism of another drug," de Graan said in a news release provided by the European Cancer Organization.
The study authors gave 30 milligrams of dextromethorphan in cough syrup form to 40 breast cancer patients and then gave them tamoxifen two hours later. Over the next 24 hours the researchers determined whether the women's bodies metabolized the drugs at similar rates. They did.
The cough medicine test needs more research and isn't ready to be used in doctors' offices, Koniaris stressed. The next steps will be to validate the research and see if the test results actually lead to better health for patients. For now, he said, "it certainly looks quite promising."
The study findings were to be released Friday at the Symposium on Molecular Targets and Cancer Therapeutics in Berlin, Germany. Research presented at meetings should be viewed as preliminary until it is published in a peer-reviewed journal.

Halaven Approved for Late-Stage Breast Cancer
Injected therapy believed to stifle cancer cell growth

HealthDay/ScoutNews LLC

MONDAY, Nov. 15 (HealthDay News) -- Halaven (eribulin mesylate) has been approved by the U.S. Food and Drug Administration to treat metastatic (spreading) breast cancer among people who have had at least two prior chemotherapy treatments for late-stage disease.

In a news release published Monday, the agency said breast cancer is the second-leading cancer cause of death of among women, citing statistics from the National Cancer Institute. Some 207,090 women are expected to be diagnosed with breast cancer this year, resulting in 39,840 deaths, the FDA said.

Halaven, derived from a sea sponge, is believed to work by inhibiting cancer cell growth. Its safety and effectiveness were evaluated in clinical studies involving 762 women with metastatic breast cancer who had had at least two prior chemotherapies for late-stage disease. Median survival was 13.1 months among those who took Halaven, compared to 10.6 months among those who didn't get the drug, the agency said.

The most common adverse reactions were a decrease in white blood cells, anemia, hair loss, fatigue, nausea, nerve damage and constipation.

IGF-1 Receptor May Present Therapeutic Target in Triple-Negative Breast Cancer

Elsevier Global Medical News. 2010 Sept 28, K Wachter

The insulin-like growth factor 1 receptor may offer a much-needed therapeutic target for triple-negative breast cancer, which can be notoriously difficult to treat.

High levels of insulin-like growth factor 1 receptor (IGF1-R) expression appears to confer a survival benefit for a subset of patients with this type of cancer, based on the results of a small study.

"In triple-negative breast cancer patients younger than 55, high expression is associated with longer survival," Dr. Agneiszka W. Witkiewicz said during a press briefing Sept. 28 sponsored by the American Association for Cancer Research (AACR).

Unlike hormone receptor-positive or HER2-positive breast cancers, triple-negative breast cancer has lacked a drug target and is managed with conventional chemotherapy. While triple-negative breast cancer accounts for only 15%-20% of breast cancer cases, it results in half of all breast cancer deaths, said Dr. Witkiewicz, a pathologist at Thomas Jefferson University in Philadelphia and an investigator on the study.

The researchers evaluated tissue from 99 women with triple-negative breast cancer. They stained the samples with anti-IGF1R antibody (Ventana Medical Systems Inc.), and scored IGF1-R protein expression according to standardized criteria originally developed to assess HER 2 expression. Patients were stratified as high expression (a score of 3) or low expression (scores 0-2).

More than a quarter of patients (29%) had high IGF1-R expression - and this was significantly correlated with negative lymph nodes. Among patients older than 55 years, there was no survival difference between those with low and high IGF1-R expression.

IGF1-R belongs to the large class of tyrosine kinase receptors that appear to control proliferation and apoptosis in tumors, and may play a role in resistance to chemotherapy. Importantly, a number of drugs targeting IGF1-R are currently under investigation in clinical trials.

The study was presented in Denver as a poster at the AACR's International Conference on Molecular Diagnostics in Cancer Therapeutic Development.

Disclosures: One of the coauthors is employed by Ventana Medical Systems, which makes an anti-IGF1-R antibody and is developing an IGF1-R probe.

10-Year Breast Cancer Survival Rates Improve
Elsevier Global Medical News. 2010 Sept 29, H Splete

Only one in four women diagnosed with breast cancer in the 1940s was alive 10 years later, compared with three of four women diagnosed in recent years, based on data gathered over a 6-decade period at a single institution.

Overall, the 10-year survival rate for all types of breast cancer improved significantly over 60 years, from 25% between 1944 and 1954, to 77% between 1995 and 2004. This improvement is because of earlier disease detection and a multimodal approach to managing and treating patients with different stages of breast cancer, Dr. Aman Buzdar, the study's lead author, reported Sept. 29.

The goal of the study was to quantify the steady improvements in breast cancer survival rates over the past 6 decades in patients seen at the MD Anderson Cancer Center in Houston. Dr. Buzdar said he believes that the survival rates seen at MD Anderson are generalizable to survival rates at smaller regional hospitals and community cancer centers, given the rapid adoption of the multimodal treatment model and new therapies.

"If patients are appropriately managed, they have a much better chance of surviving breast cancer today than they would have had 30 or 20 or even 10 years ago, because the therapies are constantly evolving and improving," Dr. Buzdar, professor of medicine and breast medical oncology at the center, said in a written statement. Therefore, if the approaches used at MD Anderson are applied in the community, similar outcomes can be achieved, he said during a press briefing sponsored by the American Society of Clinical Oncology.

Dr. Buzdar and his colleagues reviewed the center's detailed database on breast cancer patients dating back to the 1940s. The database included approximately 57,000 breast cancer patients seen between 1944 and 2004. The review included 12,809 patients who had their diagnoses established and treatments initiated at MD Anderson.

Ten-year survival rates improved significantly from the 1944-1954 period to the 1995-2004 period: For local breast cancer, the rates rose from 55% to 86% and for regional breast cancer they increased from 16% to 76%. The survival rate for metastatic disease improved from 3% to 22%.

BRCA Mutations Common in Triple-Negative Breast Cancer
Elsevier Global Medical News. 2010 Sept 30, K Wachter

The incidence of BRCA mutations in women with triple-negative breast cancer appears to be greater than previously thought, which may have important screening and treatment implications.

In all, 20% of unselected patients with triple-negative breast cancer had BRCA mutations in a small study of 77 patients. Surprisingly, the mutations were associated with significantly better recurrence-free survival and a trend toward better survival.

Moreover, all but one of the mutations were germline - that is, found only in tumor tissue - making the mutations an attractive therapeutic target, Dr. Ana M. Gonzalez-Angulo said during a press conference that was held in advance of the annual Breast Cancer Symposium sponsored by the American Society of Clinical Oncology.

The study obtained DNA from tumor and normal tissue samples that had been taken from each of 77 patients with triple-negative breast cancer. The samples had been stored in a tissue bank.

The researchers sequenced BRCA1/2 exons and flanking regions, and patients were classified as having mutant or wild-type BRCA1/2. Sequencing was performed on both tumor and normal tissue to differentiate the mutations as either germline (only in tumor tissue) or somatic (in both tissue types).

In all, 20% of patients had BRCA mutations (BRCA1 mutations, 12 patients; BRCA2 mutations, 3 patients). All but one (a BRCA1 mutation) were found only in the tumor.

Six of 14 germline mutation carriers and the one somatic BRCA1 mutation carrier had not been referred for genetic analysis. Nine of the 14 germline mutation carriers had no first-degree family history of breast or ovarian cancer.

A rate of "almost 20% mutations in an unselected population is quite high," said Dr. Gonzalez-Angulo of the department of breast medical oncology at the University of Texas M.D. Anderson Cancer Center in Houston. "So I think that we probably have to start lowering our [threshold] for at least sending these patients for genetic counseling," she said.

Dr. Jennifer C. Obel, moderator of the press briefing, agreed. "We have long known that women with BRCA mutations develop triple-negative breast cancer at a higher rate. Researchers in this study asked the flip side of the question. They found that women with triple-negative breast cancer have BRCA mutations more frequently than expected," she said.

"We may need to consider offering genetic testing to more of these patients in order to better screen them for more BRCA-associated malignancies, and to extend testing for their family members, who may also be at risk," said Dr. Obel, a medical oncologist at NorthShore University HealthSystem and a clinical faculty member at the University of Chicago.

If the findings are replicated, they may have treatment implications for triple-negative breast cancer patients.

BRCA is a DNA-repair enzyme. "So tumors that have BRCA mutations are basically very, very sensitive to agents that damage DNA," said Dr. Gonzalez-Angulo. Although there are conventional chemotherapy drugs to consider, newer investigational agents - such as PARP (ADP ribose polymerase) inhibitors - are particularly promising. Several of these agents are under investigation in clinical trials, with promising early results reported so far in breast and ovarian cancers.

BRCA1 or 2 mutations can cause errors in DNA repair that lead to breast cancer. Basically PARP-inhibiting drugs block PARP from compensating for the loss of BRCA function and from repairing DNA damage. With no functioning repair mechanism in place, the cell dies in a process called synthetic lethality.

"It may become important to identify women with these mutations because the mutation provides a rational target for treatment with PARP inhibitors - a class of drugs currently under development," said Dr. Obel.

That BRCA mutations were associated with better survival outcomes was a surprise to the investigators. Over a median follow-up of 43 months, there were 33 recurrences and 35 deaths in the study population.

The estimated 5-year recurrence-free survival rates were 51.7% for patients with wild-type BRCA 1/2 vs. 82.6% for patients with a BRCA mutation. This difference was significant.

The estimated 5-year overall survival rates were 52.8% for patients with the wild-type gene, compared with 73.3% for patients with BRCA mutations. This difference was not significant, however.

Disclosures: Three of the study authors reported significant financial relationships with Myriad Genetics Inc., a company that has a monopoly on molecular diagnostic testing for BRCA1 and 2.

On Judah Folkman and Avastin
The very miracle that gives us life can also take it away. This is what Dr. Judah Folkman discovered when he realized the mechanism of angiogenesis. Angiogenesis: the creation of a new blood supply from cells within the body. The most beautiful of angiogenesis is a fetus. The most deadly is found in cancer.

Two polar opposites, that which gives life and that which takes it away, are both developed through angiogenesis.

When Dr. Folkman made his discovery, over two decades ago, the world thought the key to unlocking the door that stops cancer had been found. However, it was not so easy. Creating an anti-angiogenesis drug proved difficult if not impossible. Until Avastin (Bevacizumab) hit the oncology world. It showed in clinical trials that it stops cancer cells from creating their own blood supply, thus stopping cancer from growing.

It was paired with other chemotherapies and there were some very good outcomes along with some deadly side effects, for some. However, it did work on women who had advanced breast cancer. It also showed promise in the treatment of early stage disease. I personally know women who benefited from this drug. It represented the future of cancer care. Until now.

This week, the FDA is considering pulling it from the market because studies show "not enough benefit compared to the risk when paired with current chemotherapies." Women who are currently benefiting from this drug will lose their insurance coverage for Avastin if the FDA succeeds in pulling this drug.

Avastin is a powerful weapon in the arsenal against breast cancer. If the FDA does not feel it works well with current, well established chemotherapies, they should have a warning for practitioners and patients alike. But they must not close the door for its use for future drugs that it may work extremely well with. One example is the new hope that is being found in Parp Inhibitors for triple negative disease. There has not been sufficient testing of Parp i, nor has there been combination trials of Avastin with these future drugs to completely rule out this hope for women who are desperate for a therapy that will extend their lives.

Pull Avastin from the market? The FDA should ask the women whose metastatic disease is now stable because of it before they close yet another door on survival. If Dr. Folkman were still alive today, he would most likely agree.

FDA May Pull Avastin From Market
Molly Peterson, BLOOMBERG News
Roche Holding AG’s top-seller Avastin may shed $1 billion in annual revenue if U.S. regulators follow a panel recommendation to revoke approval of the drug for use in breast cancer.

Scientific advisers to the Food and Drug Administration voted 12-1 yesterday to rescind Avastin’s clearance in breast cancer after finding the drug paired with chemotherapies didn’t work better than other medicines alone. The agency usually follows panels’ advice, though it isn’t required to do so.
Roche, Europe’s largest drugmaker, won FDA approval of Avastin for breast cancer in 2008 under an accelerated review that required the company to conduct trials proving the drug, with $5.97 billion in sales last year, slows progression of the disease. Tests failed to meet this goal, the FDA panel found. Withdrawal of U.S. approval could trim as much as $1 billion from annual sales by 2015, said Sanford C. Bernstein & Co. analyst Tim Anderson, in a report yesterday after the vote.

“Given the overwhelming majority against Avastin, we think there is a good chance the FDA will follow the committee’s advice,” Anderson said. He projected worldwide Avastin sales of about $6.5 billion this year, including approximately $1.2 billion from breast cancer. Eliminating U.S. breast cancer sales may cut Roche’s earnings a share by about 5 percent, he said.

No Expanded Use
Panelists also rejected Roche’s application to expand use of Avastin in breast cancer for pairings with more varieties of chemotherapy. Wider use from that approval could have pushed global breast-cancer revenue for Avastin to about $3 billion a year, said Martin Voegtli, an analyst with Kepler Capital Markets in Zurich, in a telephone interview yesterday before the panel vote.

“We are disappointed by the committee’s recommendation and believe Avastin should continue to be an option,” Sandra Horning, head of clinical development hematology/oncology at Roche said in an e-mailed statement today. “We will continue to discuss the data from the more than 2,400 women who participated in three phase III studies with the FDA.”

Roche, based in Basel, Switzerland, fell 6 Swiss francs, or 4.2 percent, to 137 francs at the 5:30 p.m. close of trading in Zurich. The stock declined 4.2 percent, the most in more than a year, July 16 after a FDA report concluded Avastin didn’t slow breast tumors in new studies as much as in earlier tests used to win approval.

“It is clear that the FDA do not believe Avastin adds a clinically meaningful benefit to patients,” said Dominic Valder, a London-based analyst with Evolution Securities, in a July 19 research report.
Sept. 17 Decision

“Today’s advisory committee vote does not change the current availability of Avastin for women with advanced breast cancer,” Charlotte Arnold, a spokeswoman for Roche’s South San Francisco, California-based Genentech unit, said yesterday in an e-mailed statement. The FDA will make a final decision by Sept. 17, she said.

Avastin is the first medicine to fight cancer by blocking the growth of blood vessels that feed tumors, a process called angiogenesis. It targets a chemical signal known as vascular endothelial growth factor, or VEGF. The treatment, also approved for brain, lung and colon tumors, costs about $50,000 a year. Avastin was developed by the company’s Genentech unit, fully acquired by the European drugmaker last year for $46.8 billion.

Most Common Malignancy
Breast cancer is the most common malignancy in females and strikes about 1 million women a year globally, according to the Geneva-based World Health Organization. Avastin is approved for about three quarters of women whose breast cancer has been recently diagnosed as having spread to other organs. It doesn’t include women who have a mutation to the HER2 protein, a known risk factor. Patients with HER2 mutations are eligible for another Roche drug, Herceptin.

The FDA’s 2008 clearance of Avastin for breast cancer overruled an advisory panel that concluded the benefit of slowing the spread of tumors wasn’t worth the risk of side effects including high blood pressure and death.

Approval was based on a clinical trial, called E2100, which showed Avastin slowed the spread of breast cancer by an additional 5.5 months when paired with paclitaxel chemotherapy, compared with the other drug alone, the FDA said in its report.

One trial completed since then, called Avado, showed that a high dose of Avastin paired with docetaxel chemotherapy extended the time patients lived without their disease worsening by 0.9 months, compared with treatment with chemotherapy alone, the FDA report said. A lower dose of Avastin gave patients 0.8 months.

Extended Life
A second trial finished after approval, called Ribbon-1, found Avastin combined with taxane or anthracycline-based chemotherapies stalled tumor growth by 1.2 months, compared with treatment with chemotherapy alone, the agency said in its review. Patients who got Avastin combined with Xeloda lived 2.9 months longer without their disease progressing, compared with chemotherapy alone.
“We have a far more comprehensive picture here of the role of Avastin than we had in 2008,” said Richard Pazdur, director of the FDA’s Office of Oncology Drug Products, told the panel before yesterday’s vote.

Drugs that win conditional clearance through the FDA’s accelerated-approval program can later be pulled from the market if subsequent data fails to show that a treatment increases long-term survival or slows progression of the disease while improving quality of life.

‘Overwhelming Majority’
While Avastin is expensive and doesn’t work as well as early trials suggested, the “overwhelming majority” of breast cancer specialists think the drug has a use in certain patients, Jack Scannell, a Bernstein analyst in London, said in a July 15 research note.

Breast-cancer patients may lose insurance coverage for Avastin if the FDA revokes approval of the treatment, said Francisco Esteva, a professor of breast medical oncology at the University of Texas MD Anderson Cancer Center in Houston.

“Even if we wanted to use it, patients would have to consider that it’s a very expensive therapy,” Esteva said July 15 in a telephone interview. “Without insurance support, I don’t think patients would be able to take it.”

We have written several articles, blog posts and shared too many personal stories to take this anymore. Women are not getting early screening for breast cancer and that means their cancers are being found too late. They are found spread to lymph nodes and distant organs - found too late to treat - too late to do anything that could be prevented.

We do NOT have a cure yet. Until then, it is up to US, to take the pledge and save the lives of women who do not even know they have breast cancer: Because early detection is our ONLY DEFENSE.

Are you ready?
Take the Before Forty Initiative Pledge!

Mammogram uproar as pols, doctors reject guidelines
Originally published: July 11, 2010 6:32 PM Updated: July 11, 2010 9:42 PM

Eight months ago, a federal advisory panel triggered an uproar by saying most women needed fewer mammograms and should begin them at a later age. Today, the confusion over those guidelines has intensified as physicians and lawmakers demand they be withdrawn.

The recommendations suggested women without risk factors for breast cancer could wait until 50 to start annual screening. Within a day of their release, Health and Human Services Secretary Kathleen Sebelius issued a statement saying the guidelines didn't represent government policy, and advised women to "do what you've always done."
But the guidelines from the U.S. Preventive Services Task Force, a panel of outside experts chosen by HHS, are still posted on an official government website run by Health and Human Services although they have been modified slightly to say women between 40 and 49 who want a mammogram should get one if their doctor recommends it.
Still, the furor over the guidelines will not go away.

Sen. David Vitter (R-La.) wrote to Sebelius in May saying passage of the Patient Protection and Affordable Care Act in December required that the government withdraw the guidelines.

Vitter said the bill, passed by a bipartisan vote, called on HHS to remove the recommendations from its website and "cease all promotion of the November 2009 recommendations related to breast cancer screening and mammography"
In his letter, he wrote: "The fact that these recommendations are still being presented to the general public as 'current' is only serving to further confuse women on this critical issue. The recommendations were ill-conceived from the start. . . . They represent a step backward in our fight against a horrible disease."

Vitter spokesman Joel DiGrado said they have yet to receive a reply from Sebelius. "The senator's office has not heard anything back from HHS. This is not all that untypical for an agency. Their responses to formal letters can take quite some time."
Newsday made several attempts to get HHS to address the status of the guidelines - whether the agency still endorses them now that they've been edited, or whether they will be withdrawn, as some lawmakers are seeking. The agency did not provide answers to the questions and no one from HHS would address whether scrapping the guidelines is seriously under discussion.

Dr. Christine Hodyl, director of breast surgery at South Nassau Communities Hospital in Oceanside, said she never took the guidelines seriously - they're unrealistic for Long Island.

"This week alone," she said recently, "I operated on two women. One was 37 and the other was 41. Here on Long Island, the breast cancer rate is so high I tell women to get their baseline [first mammogram] at 35 to 40. If these [two] women had waited until 50, the cancer would have metastasized."

Another critic, Dr. Brian O'Hea, director of the Carol M. Baldwin Breast Care Center at Stony Brook Medical Center, said he never stopped recommending routine screening at age 40. "We're still in line with the American Cancer Society and have not changed a bit," O'Hea said.

Last month, a Harvard mammography expert charged that the guidelines are based on faulty science and should be retracted.

None of the task force members were experts in breast cancer or mammography.
Health care insurers, such as Empire BlueCross Blue-Shield and Vytra, say they are sticking with the cancer society's recommendations.

There is now proof that the US Task Force has done damage. This group of people announced in the fall that women under 50 years of age do not need mammograms. The No Surrender Breast Cancer Foundation is vehemently against this decision and has made our opinion known.

Before Forty Initiative is  working hard to get the word out to all women that Early Detection is your BEST defense. If you want the highest chance of beating cancer: find it while it is still small. That is why we are educating women about the importance of baseline screenings BEFORE the age of Forty and follow-up care that involves not only mammography, but ultra sound and breast MRI.

We need your help to help us save the lives of women.

Please see our

DONATE to our foundation to help us. We need funding.

Read today's news, and you will find more proof why it is our duty to protect the women who come after us.

Mammogram screening down 13 percent since 'flawed' recommendations
By Aimee Heckel Camera Staff Writer
Posted: 06/23/2010 09:14:36 AM MDT

Read more:
Mammogram screening down 13 percent since 'flawed' recommendations - Boulder Daily Camera

Terry Stiven, of Lafayette, almost didn't get the test.
She had no family history of breast cancer. She'd had mammograms in the past, and she had no signs of cancer.

Then, this fall, the United States Preventative Service Task Force released new recommendations: Women between 40 and 49 years old don't need mammograms. The benefits of testing don't outweigh the risks, the task force said.

Now, it seemed there was no reason to get the 10-minute, slightly uncomfortable screening. In February, Stiven, 46, went ahead and got tested anyway, expecting nothing.
She had cancer.

Not invasive breast cancer, though. Doctors removed the lump, and she had four weeks of radiation. The experience was frightening, but not damaging.

Today -- just four months later -- Stiven is cancer-free, with extremely low chances of it returning. She still has both breasts, she runs triathlons and her life expectancy has not been shortened.

"If I'd waited four years, I don't know if I would have been alive," she says.
Stiven is one reason of many that local doctors have launched an aggressive campaign to counter the U.S. Preventative Task Force's advisory.

"Getting a mammogram is one of the most important things a woman can do to live a long, healthy life," says David Oppenheimer, the chief physician of the mammography department of the Boulder Community Hospital.

And he's not just talking about women older than 50.

One third of women diagnosed with breast cancer in Boulder County are between 40 and 49 years old, according to the Boulder Community Hospital. More than 40 percent are younger than 50 -- the task force's "arbitrary" age cut-off, Oppenheimer says.

Since the task force's recommendation, the hospital's imaging department reports a 13 percent decline in mammograms -- the majority among women in their 40s and 50s.

Nanna Bo Christensen, the Boulder Community Hospital's Breast Health Navigator, attributes this drop at least in part to the national recommendation.

Other women may be afraid they can't afford it -- even though it is illegal in Colorado for insurance companies not to cover screenings for women age 40 and older. The Women's Wellness Connection offers financial support for women who need it, too, says Christensen.

"Mammography saves lives," she says. "The key to survival is early detecting."

In fact, the younger the woman, the faster the breast cancer grows, doctors say, due to higher levels of estrogen, which feeds the cancer cells.

And if you find cancer before it spreads to the lymph nodes, Oppenheimer says, doctors have a 97 percent chance of curing it. Once it hits the lymphs, the cure rate plunges.

The number of women who die from breast cancer is down since 1990, and experts say that's primarily due to increases in the number of women being screened.

So why would a government panel recommend against something that statistics show helps save lives?
The task force looked at false-positive tests and the related anxiety, unnecessary biopsies and exposure to radiation.

Oppenheimer asserts data used for the recommendation was scientifically flawed, and that the task force left out several important studies to skew the numbers in favor of its recommendation. As to the radiation question, he says about 1 in 3 million mammograms actually causes cancer.

"However, we know that one in eight women are going to get breast cancer in their lives, so the advantages far outweigh the tiny risk," he says.

Mammograms detect cancer 90 percent of the time, the hospital says, making them the most effective screening tool.

A slew of organizations have since denounced the recommendation, including the National Cancer Institute, the American Cancer Society, the Susan G. Komen Breast Cancer Foundation, Avon Foundation, the Obama Administration, American College of Radiology, American Society of Breast Imaging, American College of Obstetricians and Gynecologists.

"Now we as physicians and a health care community have a huge job on our hands to re-educate the community," Oppenheimer says. "Once people stop getting tested, it's a huge effort to convince people to start again."

The U.S. task force also said women older than 50 only need to get a mammogram every two years instead of annually.

When Jill Kamon, of Boulder, heard that, she says she was horrified.

Kamon was diagnosed at age 51 with breast cancer. If she had followed the recommendations, she would have skipped the mammogram that found the small lump in the back of her breast. The cancer would have had a year to grow before her next mammogram. She couldn't feel it with a self-exam.

"To me, the mammogram and radiologist who read the mammogram completely saved my life. There is no question," says Kamon, who had a double mastectomy in the summer of 2007. The lump was only 6 millimeters big, but it was growing aggressively.

"I'd had a mammogram exactly one year earlier that was clear," she says. "That dot was not there."

By the numbers
13 percent -- Decrease in mammograms at the Boulder Community Hospital since the U.S. 
Preventative Service Task Force recommendation in the fall. The majority of these women are in their 40s and 50s.
30 percent -- Decrease in breast cancer's death rate since 1990, nationally.
42 percent -- Of women diagnosed with breast cancer at the Boulder Community Hospital were younger than 50; 32 percent were in their 40s.
More than 30 percent -- Decreased death rate, due to mammography screenings for women in their 40s.
One in eight -- American women are affected by breast cancer.
97 percent -- Chance of curing breast cancer if it's caught before spreading to the lymph nodes.
About 1 in 3 million -- Chance of the radiation from a mammogram causing breast cancer.
Sources: Boulder Community Hospital, Susan G. Komen for the Cure.

Important information for Tamoxifen Users
OncologySTAT has released this very important discussion about CYP2D6 enzyme and tamoxifen. Be aware that there are drugs you may be taking that could render Tamoxifen powerless, leaving you vulnerable for breast cancer recurrence.

Dr. Matthew P. Goetz: Tamoxifen Metabolism, Endoxifen, and CYP2D6 Polymorphism
2010 Jun 15, Interview by L Scott Zoeller
Please go to
THIS LINK for more information.

Get moving after breast cancer surgery...
See our post surgical exercises

Exercise Preserves Freedom of Movement After Breast Cancer Surgery

Washington, June 16 (ANI): A study has found that exercise can help patients maintain shoulder movement and minimize loss of arm or shoulder function after breast cancer surgery.
The new Cochrane review found exercise programs needed to be created to help patients who have just had surgery, as most survivors develop pain, shoulder stiffness and arm swelling after treatment.

Physicians usually prescribe arm and shoulder exercises after surgery to prevent pain and stiffness in those areas on the side of the cancer, but the problems often persist for years.

"There has been some concern that too much aggressive movement soon after surgery might cause pain, delay healing, and increase the risk of arm swelling," said lead review author Margaret McNeely, an assistant professor of physical therapy at the University of Alberta and clinical researcher at the Cross Cancer Institute, in Canada.

McNeely's team examined 24 research studies comprising 2,132 women with a confirmed breast cancer diagnosis and who had undergone surgery such as a radical mastectomy, modified radical mastectomy, or a local wide excision or lumpectomy.

They had also all had surgery removing lymph nodes from the axilla, or armpit, to determine the extent of the cancer.

Specially designed programs included range-of-motion movements for the shoulders and stretching exercises.

The review showed that starting exercise early after surgery, within the first to third day, might result in better shoulder movement in the early weeks following surgery.

"However, starting exercise that soon after surgery may cause more wound drainage and require drains to remain in place longer than if exercise is delayed by about one week," McNeely said.

The Cochrane Collaboration, an international organization that evaluates medical research, published the review.

Fourteen studies compared the effect of structured exercise to usual care, in which women received an exercise pamphlet or no exercise instruction at all.

Of these, structured programs including physical therapy regimens in the early postoperative period led to a significant improvement in shoulder range of motion over the short and long term.

"Several persistent complications can greatly diminish a patient's quality of life," said Douglas Blayney, M.D., medical director at the University of Michigan's Comprehensive Cancer Center.

Blayney said that although current surgical treatment is attempting to move away from disturbing the axilla, more women, especially younger women, are choosing mastectomy over breast conserving surgery.

"Combined, these trends in primary treatment of breast cancer make this review highly relevant," said Blayney, who has no affiliation with the review.

Nevertheless, he noted that making suitable exercise programs widely available to breast cancer patients in a timely manner would be a challenge.

He said optimal breast cancer care now involves a team with a wide range of health specialists: surgeons, radiation oncologists, medical oncologists, reconstructive surgeons and others.

"This review demonstrates that early involvement of a new team member who manages exercise or physical therapy is also useful for the best outcome," he said.

"Implementation of modern primary treatment strategies - - including early intervention with suitable exercises - should reduce the incidence of these heartbreaking complications," Blayney added. (ANI)

Sequential seems superior...
Longer Therapy, Iatrogenic Amenorrhea, and Survival in Early Breast Cancer
N Engl J Med. 2010 Jun 3;362(22):2122-2124, SM Swain, JH Jeong, CE Geyer Jr, JP Costantino, ER Pajon, L Fehrenbacher, JN Atkins, J Polikoff, VG Vogel, JK Erban, P Rastogi, RB Livingston, EA Perez, EP Mamounas, SR Land, PA Ganz, N Wolmark
In this study that enrolled more than 5000 women with early-stage, node-positive, operable breast cancer, chemotherapy with sequential-ACT improved both DFS and OS when compared with four cycles of doxorubicin/docetaxel...

Background: Chemotherapy regimens that combine anthracyclines and taxanes result in improved disease-free and overall survival among women with operable lymph-node-positive breast cancer. The effectiveness of concurrent versus sequential regimens is not known.

We randomly assigned 5351 patients with operable, node-positive, early-stage breast cancer to receive four cycles of doxorubicin and cyclophosphamide followed by four cycles of docetaxel (sequential ACT); four cycles of doxorubicin and docetaxel (doxorubicin-docetaxel); or four cycles of doxorubicin, cyclophosphamide, and docetaxel (concurrent ACT). The primary aims were to examine whether concurrent ACT was more effective than sequential ACT and whether the doxorubicin-docetaxel regimen would be as effective as the concurrent-ACT regimen. The secondary aims were to assess toxic effects and to correlate amenorrhea with outcomes in premenopausal women.

Results: At a median follow-up of 73 months, overall survival was improved in the sequential-ACT group (8-year overall survival, 83%) as compared with the doxorubicin-docetaxel group (overall survival, 79%; hazard ratio for death, 0.83; P=0.03) and the concurrent-ACT group (overall survival, 79%; hazard ratio, 0.86; P=0.09). Disease-free survival was improved in the sequential-ACT group (8-year disease-free survival, 74%) as compared with the doxorubicin-docetaxel group (disease-free survival, 69%; hazard ratio for recurrence, a second malignant condition, or death, 0.80; P=0.001) and the concurrent-ACT group (disease-free survival, 69%; hazard ratio, 0.83; P=0.01). The doxorubicin-docetaxel regimen showed noninferiority to the concurrent-ACT regimen for overall survival (hazard ratio, 0.96; 95% confidence interval, 0.82 to 1.14). Overall survival was improved in patients with amenorrhea for 6 months or more across all treatment groups, independently of estrogen-receptor status.

Conclusion: Sequential ACT improved disease-free survival as compared with doxorubicin-docetaxel or concurrent ACT, and it improved overall survival as compared with doxorubicin-docetaxel. Amenorrhea was associated with improved survival regardless of the treatment and estrogen-receptor status.

Liver Mets? Consider Surgery
Liver Resection for Multimodal Treatment of Breast Cancer Metastases: Identification of Prognostic Factors
Ann Surg Oncol. 2010 Jun 1;171546-1554, K Hoffmann, C Franz, U Hinz, P Schirmacher, C Herfarth, M Eichbaum, MW Büchler, P Schemmer

In this retrospective analysis of patients with hepatic metastases from breast cancer who underwent exploratory laparotomy, the 5-year overall survival rate after liver resection was 48%.

Supplementary editorial provided by OncologySTAT
In this retrospective analysis of patients with hepatic metastases from breast cancer who underwent exploratory laparotomy, the 5-year overall survival rate after liver resection was 48%.

The role of liver resection (LR) is controversial as a component of multimodal therapy for hepatic metastases (HM) associated with breast cancer. Thus, a better understanding of the benefits and clinical outcomes of the surgical approach is needed, along with identification of the potential prognostic factors for long-term survival.

To this end, Hoffmann et al. retrospectively evaluated data that were prospectively collected for 41 patients with hepatic breast cancer metastases. All of these patients underwent exploratory laparotomy for LR. Of the 41 patients, 40 patients had primary tumor adenocarcinoma, and 1 patient had a mucinous carcinoma of the breast. Patients selected for hepatic resection were stable, having no more than five metastases and with extrahepatic metastases under remission. No vascular invasion was evident, and R0 resection was deemed possible. Karnofsky index was ≥80%.

The median time from treatment of the primary breast tumor to diagnosis of HM was 3.4 years (interquartile range [IQR], 1.2–8.0 years). Segment resections were performed in 19 patients (45%) and major hepatectomy was performed in 22 patients (right hemihepatectomy, 25%; left hemihepatectomy, 12%; extended right hemihepatectomy, 7%; extended left hemihepatectomy, 9%).

The primary outcome measure was overall survival from the date of LR. Secondary outcome parameters were disease-free survival, progression-free survival, and recurrence-free survival from the date of LR and overall survival from the date of primary breast tumor operation.

Median follow-up was 34 months after LR (IQR, 8–68 months). The estimated median survival was 58 months. The 3- and 5-year survival rates after LR were 68% and 48%, respectively, although they were 80% and 59%, respectively, from the time of diagnosis of HM, with an estimated median survival of 79 months. The 5-, 10-, and 15-year survival rates after treatment of the primary tumor were 84%, 76%, and 50%, respectively, with a median survival of 211 months. Incidence of HM earlier than 12 months after treatment of the primary tumor (5-year overall survival, 28%) was associated with a three-times-higher likelihood of mortality (hazard ratio, 3.8) compared with HM occurring later than 1 year after treatment of the primary tumor (5-year overall survival, 58%). R0 resection resulted in 3- and 5-year survival rates of 80% and 62%, respectively, while patients after R1/R2 resection had a median survival of 28 months after LR, with patients six times more likely to die compared with patients after R0 resection (hazard ratio, 6.3).

In the absence of extrahepatic metastases at the time of LR, the 3- and 5-year overall survival rates were 75% and 59%, respectively, compared with rates of 51% and 31%, respectively (P = 0.15), for patients who did have extrahepatic metastases.

Following R0/R1 resection, patients without extrahepatic disease at the time of LR (n = 26) had an estimated median disease-free survival of 34 months; the 3- and 5-year disease-free survival rates were 46% and 31%, respectively, with HM reducing the respective rates to 26% and 13%.

The median time to intrahepatic recurrence in patients without extrahepatic disease at the time of LR was 8.6 months; the 3- and 5-year intrahepatic recurrence-free survival rates were 71% and 62%, respectively.

The results of this study showed that, in patients with hepatic breast cancer metastases (without any type of peritoneal carcinomatosis and/or positive hilar lymph nodes), LR was safe and improved long-term survival. No perioperative deaths occurred during this study.

Check that label first...
Some sunscreens contain dangerous chemicals
June 4, 2010 3:10 PM

We all know it's important to use sunscreen. But it's also important to check the label for ingredients that are safe for you and the environment.

The Environmental Working Group, a nonprofit public health and environmental research and advocacy organization based in Washington, D.C., studied nearly 1,000 brand-name sunscreens in 2009. Three in five did not adequately protect skin from the sun or contained harmful chemicals.

One controversial sunscreen ingredient is oxybenzone. It absorbs ultraviolet light, but research shows it also can be absorbed through the skin. The Centers for Disease Control and Prevention released a study in 2008 showing that 97 percent of Americans it tested were contaminated with oxybenzone.
Oxybenzone is allowed in sunscreens, but recent research has linked it to allergies, hormone disruption and cell damage that can lead to skin cancer. It's bad for the environment, too. Researchers believe oxybenzone, once washed down the drain or off swimmers' bodies, contributes to the feminizing of certain species of male fish in our oceans, rivers and lakes.

So why is oxybenzone still considered "safe" in sunscreens? Unfortunately, the Federal Drug and Food Administration, which regulates sunscreen safety, has not updated mandatory sunscreen standards in more than 30 years.

What should you do? Look for a broad-spectrum sunscreen that offers protection from both UVA and UVB rays but does not contain oxybenzone.
Sunscreens containing zinc oxide or titanium oxide are recommended by the Environmental Working Group.

Emerging studies show that we are out of balance with too much Omega 6 verses the healthy Omega 3s. Extra virgin olive oil helps us regain that balance. Stay away from other fats and processed foods and you will not only feel the difference, but you will see it, too.
Breast Cancer Survivors Lose More Weight On Olive-Oil Enriched Diet
04 Jun 2010
Researchers from The Miriam Hospital have found that olive oil may offer another potential health benefit - it produces greater weight loss in breast cancer survivors compared to a more traditional low-fat diet.

The findings may be of significance to women with breast cancer, since excess weight at the time of diagnosis, or even moderate weight gain during cancer treatment, is associated with an increased risk of cancer recurrence, particularly in post-menopausal women.

In this pilot study, women followed two 1,500-calorie diets - a conventional low-fat diet recommended by the National Cancer Institute (NCI) and a plant-based olive oil diet similar to the Mediterranean diet. After eight weeks on each diet, participants selected one diet to follow for an additional six months of continued weight loss or weight management.

According to the findings, published in the June issue of the Journal of Women's Health, 80 percent of women who started with the plant-based olive oil diet lost more than 5 percent of their baseline weight, compared to 31 percent who started with the NCI diet. But researchers were most surprised to find that after trying both diets, most women chose to stick with the less conventional, higher fat olive oil diet, saying they found the food more appetizing, accessible and affordable.

Mary Flynn, PhD, RD, LDN, the study's lead author and a research dietitian at The Miriam Hospital, says many breast cancer patients don't realize there is a link between weight and cancer recurrence.

"That's why it was important for us to compare these two diets and determine which one the women not only enjoyed following, but also produced the best weight loss, because that's the diet they're more likely to stick with," says Flynn. "In this case, it was a diet enriched with extra virgin olive oil, which is a source of healthy fats, and includes foods associated with improving one's health, such as vegetables, beans and other plant products."

Extra virgin olive oil has been associated with decreasing breast cancer risk in Greece, Spain and Italy, where it is consumed in great quantities. Many studies have also demonstrated the cancer protective properties of carotenoids, a phytonutrient found in the red, orange and yellow pigments of fruits and vegetables. The NCI lists obesity as a risk factor for disease recurrence but does not recommend a specific diet for weight loss, although it has consistently recommended lowering dietary fat to prevent breast cancer.

Flynn developed the olive oil diet used in the study, which included at least three tablespoons of olive oil per day, with nuts at breakfast. Women also ate three servings of fruit and unlimited vegetables daily, and whole grains were also emphasized. Women could eat limited amounts of poultry and fish per week but red meat and polysaturated fats, like vegetable oils, were prohibited.

Because the NCI-recommended low-fat diet is not as specific, women had a less restrictive meal plan. Their diet consisted of at least five servings of fruits and vegetables, approximately 25 to 50 grams of fat (including canola oil) and six to seven ounces of lean meat (not red meat) daily.

The study included 44 overweight women (BMI of at least 25) diagnosed with invasive breast cancer after the age of 50 who were within four years after completing treatment. The order of the diets was randomly assigned, and participants followed each diet for eight weeks. Women were provided with meal plans and recipes for each diet and were asked to keep three-day food diaries at weeks four and eight of each diet and during months three and six of the follow-up period. Weight was measured and blood samples were taken at the end of each study period.

Overall, 28 of the 44 women completed both diets and 19 of the 22 eligible for the six months of follow-up chose to follow the plant-based olive oil diet. All 19 women either maintained their weight loss or lost additional weight during this time.

"I found this surprising, particularly since the low-fat diet is more commercial and more recognizable to women, so I thought the preference would be more evenly split," says Flynn, who is also an assistant professor of medicine at The Warren Alpert Medical School of Brown University. "But the women who enjoyed the olive oil diet said not only were they losing weight but they weren't as hungry. That's because they were advised to include fat in the form of olive oil or nuts at each meal, so they weren't as likely to snack between meals, which can cause weight gain."

As researchers expected, the plant-based olive oil diet also resulted in lower triglycerides (a type of fat found in the blood) and higher high-density lipoprotein cholesterol (HDL, or "good" cholesterol). High triglycerides and low levels of HDL have both been linked with increased cancer risk.

The study was supported by a grant from The Susan G. Komen for the Cure Foundation. Steven E. Reinert, MS, from Lifespan Information Services, was co-author on the study.

Source: Lifespan

Copyright: Medical News Today

Scientific Proof helps us promote our Before Forty Campaign...
Breast Cancer Screening: MRI Sensitive, No Added Value With Mammography, Study Suggests

ScienceDaily (Mar. 8, 2010) — Do we need a revision of current recommendations for breast cancer screening? According to a recent prospective multicenter cohort study published in the Journal of Clinical Oncology, this appears advisable at least for young women carrying an increased risk of breast cancer. The results of the EVA trial confirm once more that magnetic resonance imaging (MRI) is substantially more accurate for early diagnosis of breast cancer than digital mammography or breast ultrasound: MRI is three times more sensitive for breast cancer than digital mammography.

For the EVA trial, almost 700 women were enrolled. Aim of the trial was to refine existing guidelines for surveillance of women at high and moderately increased risk of breast cancer. Findings suggest that in these women, MRI is essential for early diagnosis -- and that a mammogram or an ultrasound examination does not increase the "cancer yield" compared to what is achieved by MRI alone. Researchers conclude that annual MRI is not only necessary, but in fact sufficient for screening young women at elevated risk of breast cancer. In women undergoing screening MRI, mammograms will have no benefit and should be discontinued. Moreover, MRI screening is important not only for women at high risk, but also for those at moderately increased risk.

Between 2002 and 2007, the EVA trial recruited 687 women who carried a moderately increased risk of breast cancer (lifetime risk of 20% and over). Women underwent 1679 screening rounds consisting of annual MRI, annual digital mammography and half-annual screening ultrasound examinations. During this time span, 27 women received a new diagnosis of invasive cancer or DCIS (Ductal Carcinoma In Situ).

Of all imaging methods under investigation (digital mammography, ultrasound and MRI), MRI offered by far the highest sensitivity: MRI identified 93% of breast cancers. 37% of cancers were picked up by ultrasound. The lowest sensitivity was achieved by digital mammography, which identified only one-third of breast cancers (33%). These results confirm once more that MRI is essential for surveillance not only of women at high risk, but also for women at moderately increased risk of breast cancer. Moreover, the results contradict current guidelines according to which mammography is considered indispensable for breast cancer screening. One aim of the EVA trial was to question this concept and to ask whether it is still appropriate to require that MRI should only be used in addition to mammography. The results speak for themselves: If an MRI is available, then the added value of mammography is literally negligible. Researchers conclude that MRI is necessary as well as sufficient for screening young women at elevated risk of breast cancer. Since mammography appears to be unnecessary in women undergoing MRI, its use is no longer justifiable, and current guidelines should be revised to reflect this.

Current guidelines questionable

Current guidelines for women at high familial risk of breast cancer recommend annual MRI (with or without ultrasound) and annual MRI starting at age 25-30. "These guidelines were set up based on little or no scientific evidence, and mainly reflect expert opinion," summarizes Prof. Christiane Kuhl, radiologist at the University of Bonn and principal investigator of the EVA trial. "In the light of the results of the EVA trial, such recommendations should be revisited." This seems even more important because digital mammography uses x-rays (ionizing radiation) to detect breast cancer. "The radiation dose associated with regular mammographic screening is clearly acceptable and safe," underscores Kuhl. "However, regular mammographic screening usually starts at age 40-50." The situation is different if systematic annual mammographic screening is started at age 25-30. "Not only because these women will undergo more mammograms and therefore will experience a cumulative lifetime radiation dose that will be substantially higher, but also because the breast tissue of young women is more vulnerable to the mutagenic effects of radiation." This appears to be especially true for BRCA mutation carriers. "Accordingly, we impose more radiation on less radiation-tolerant breast tissue -- for a very limited, if any, diagnostic benefit." Therefore, Kuhl advocates a revision of existing guidelines: "It is no longer justifiable to insist on annual mammographic screening women in their thirties if they have access to screening MRI."

MRI is a mature technology

In the past, MRI was used strictly in addition to mammography only. The allegedly high rate of "false positive" diagnoses and the allegedly insufficient sensitivity for DCIS were the main reason to discourage its use as a stand-alone method for breast cancer screening. "In this multicenter trial, with basic quality assurance implemented not only for mammography, but also for MRI, we were able to prove that false positive diagnoses are avoidable if MRI studies are interpreted with adequate radiologist expertise." In the EVA cohort, the Positive Predictive Value achieved with MRI was already even higher than that of mammography or breast ultrasound. "Moreover, we found that MRI offered the highest sensitivity especially for DCIS," adds Dr. Kuhl. "It is simply wrong to state that we need a mammogram to detect intraductal cancer."

Kuhl et al. Prospective Multicenter Cohort Study to Refine Management Recommendations for Women at Elevated Familial Risk of Breast Cancer: The EVA Trial. Journal of Clinical Oncology, 2010; DOI: 10.1200/JCO.2009.23.0839

Targeted therapy for TNBC...this could be big

This could be big. Breast cancer is not one disease as we all know. Triple Negative Breast Cancer has been on the back burner in terms of new therapies, until now. PARP treatment is changing the future of metastatic TNBC patients. Now, a new, targeted therapy has identified a sub-type of TNBC tumors...

New Subtype of Breast Cancer Responds to Targeted Drug
ScienceDaily (Mar. 2, 2010) — A newly identified cancer biomarker could define a new subtype of breast cancer as well as offer a potential way to treat it, say researchers at Washington University School of Medicine in St. Louis.

Their findings will be published in the March 1 online early edition issue of the Proceedings of the National Academy of Sciences.

The research could further refine what recent breast cancer research has concluded: that breast cancer is not one disease, but many. So far, research has firmly established that at least five subtypes of breast cancer exist, each having distinct biological features, clinical outcomes and responses to traditional therapies.

The biomarker identified by the Washington University researchers is found frequently in breast cancers and especially in those that have poorer outcomes. It stems from overactivation of a gene called LRP6 (low-density lipoprotein receptor-related protein 6), which stimulates an important cell-growth signaling pathway. LRP6 can be inhibited by a protein discovered in the same laboratory, which could become an effective drug against the breast cancer type, the researchers say.

"We found increased expression of the LRP6 gene in about a quarter of breast cancer specimens we examined, and we think LRP6 overexpression could be a marker for a new class of breast cancer," says Guojun Bu, Ph.D., professor of pediatrics and of cell biology and physiology. "In addition, we found that this biomarker is often associated with breast cancers that are either harder to treat or more likely to recur. We already have an agent that seems to be effective against LRP6-overexpressing tumors, which could someday become a therapy for tumors that right now have few treatment options."
The research was conducted primarily by Chia-Chen Liu, a graduate student in the Bu lab, who is a fellow in the Cancer Biology Pathway Program at the Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital.

The researchers' analysis of human breast cancer tissue samples found significant increases in LRP6 levels in 20 percent to 36 percent of the tumors. LRP6 was increased more frequently in ER (estrogen receptor)-negative or HER2 (human epidermal growth factor receptor 2)-negative samples. LRP6 was also increased more frequently in so-called triple-negative breast tumor samples, which test negative for ER, HER2 and PR (progesterone receptor).

In general, patients who have triple-negative breast cancers have an increased risk of disease recurrence after initial treatment and a poorer prognosis. Furthermore, although ER-positive and HER2-positive tumors can be targeted with specific therapies, ER-negative and HER2-negative tumors cannot. So it appears that LRP6 overexpression is often associated with tumors that are currently difficult to treat, says Bu.

Research in the lab had earlier discovered a protein that binds to and inhibits LRP6. This study showed that the protein, called Mesd (mesoderm development), was able to slow the growth of breast cancer cells in the laboratory and to inhibit mammary tumor growth in laboratory mice.

Importantly, mice treated with Mesd did not experience any of the known side effects, such as bone lesions, skin disorders or intestinal malfunctions, associated with inhibition of this growth pathway.
"Our work introduces Mesd as a promising antitumor agent that might be further developed for breast cancer therapy," Bu says. "It would be analogous to such successful breast cancer therapies as Herceptin (trastuzumab), which specifically targets HER2-positive breast cancer."

The researchers also found that a small segment of Mesd has the same effect as the larger molecule. This segment, or peptide, is more stable than the whole protein molecule and can be easily synthesized.

The researchers have patented the protein and the peptide through the university's Office of Technology Management. Recently, Raptor Pharmaceutical Corp. licensed Mesd from the university to develop it for clinical use.

Funding from the National Institutes of Health and the Siteman Cancer Center supported this research.

Got Hope? TNBC patients do now!

The Reviews Are in:
Blockbuster drug known as PARP = A future of hope

"I believe that in the next two to three years, PARP inhibitors will do for triple-negative breast cancer what trastuzumab [Herceptin] did for HER2 breast cancer." Jenny Chang, Baylor

"This development may have the potential to change patient survival . . . and appears to potentially change the natural history of at least a subclass of metastatic breast cancer [TNBC]" Clifford Hudis, MSK

“When you go home, be excited. Be really excited about this. Tell your patients there is reason to be hopeful.” Eric Winer, Dana Farber

Until now, the treatment for triple negative breast cancer has been limited. The options for metastatic patients were few and far between. Until now. The first completed studies of PARP, have shown that not only does it slow progression of disease, but patients are experiencing a complete response to the drug.

The side effects of PARP are generally well tolerated and do not include hair loss.

Where once there was no hope, no magic drug for triple negative patients, PARP is proving itself to be, as Dr. Jenny Chang, of the Baylor School of Medicine said, “What Herceptin did for HER2 breast cancer.”

“Many experts have argued that it is not possible to change survival in stage IV breast cancer. Certainly now there evidence for an alternative viewpoint; that with the use of very effective drugs, we can change overall survival, and we should aim for that." Clifford Hudis, MSK

For more information, speak to your oncologist. For information on recruiting trials for PARP click the following links:

Chang C.  Interview with Neil Love.  in Conversations with Oncology  Investigators - Bridging the Gap between Research and Patient Care.  Breast Cancer Update 2009;8(6):3-6 [Track 5; with audio].

Hudis C.  Interview by L Scott Zoeller 2009 Oct 21.  Extended Survival With PARP Inhibitors Changes Expectations in Metastatic Breast Cancer.  Viewpoints.  In OncologySTAT 2009.

Carlson R.  PARP Inhibitors Show Promise Against Metastatic Triple-Negative Breast Cancer in Early Studies.  Oncol Times 2009;31(15):10-11.

Genomic project zeroes in on TNBC...

Triple Negative Breast Cancer News: Genome Project

Background: Drug companies have developed an array of drugs to attack cancer and other conditions influenced by genetics, but it’s difficult to tell which patients will respond to which drugs.

What’s happening: A new study will sequence the genomes of cancer tissue from 14 breast cancer patients whose tumors have progressed despite multiple treatments.

The future: Proponents of “genomic medicine” think it will become increasingly possible to use sequencing to steer individual patients to the drugs most likely to work.

A Carlsbad biotechnology company is helping launch an unusual cancer study that may eventually lead to doctors tailoring treatments to patients’ genes. Life Technologies says the study — involving sequencing the genomes of 14 patients with a tough-to-treat form of breast cancer — is a step toward a future of “genomic medicine,” a decade after the sequencing of the first human genome.

It’s evidence of how quickly work in this area is progressing, with the $2.6 billion that went into the Human Genome Project reduced to $6,000 per genome on Life Technologies’ latest sequencing instrument. “This is a pretty amazing example of how far these tools of genomics are moving into direct patient applications,” said Jeffrey Trent, president of the Phoenix-based Translational Genomics Research Institute, which is working with Life Technologies on the project.

The company will announce the study today to coincide with the opening of a two-day conference on genomic medicine in La Jolla, at which experts will discuss the latest breakthroughs and the outlook for more advances in the field. Already, biotechnology research has created numerous drugs that target genetic problems that lead to cancer and other conditions. In the case of breast cancer, at least a dozen such drugs are on the market, said Dr. Daniel
D. Von Hoff, physician-in-chief at the translational genomics institute. A big problem, however, is that it’s difficult to predict which drugs will work for a particular patient. That’s where sequencing is supposed to help.

“For those mutations for which we do have drugs, we can help the physician make more informed decisions than they’re making today,” said Linh Hoang, director of personalized medicine at Life Technologies.
The study could also help scientists identify promising areas to explore for future drugs. It’s impossible to know ahead of time whether the 14 patients have genetic patterns that current drugs address, but researchers will also look for similarities in the DNA of the 14.

“It may lead to more targets that pharmaceutical companies will want to design drugs around,” Hoang said.
The study will involve patients with what’s known as triple-negative breast cancer whose tumors have progressed despite multiple therapies. That type of cancer makes up about a fifth of breast cancer cases and doesn’t respond to common drugs, such as Herceptin. Patients will be enrolled by U.S. Oncology, a Houston-area company that specializes in cancer-treatment services, and Von Hoff said the plan is to take the first 14 people who meet the study criteria.

A spokeswoman for U.S. Oncology said the company plans to enroll patients from about a half-dozen of its sites with the highest incidences of triple-negative cases. Sites in Colorado, Oregon, Texas and Virginia have already been identified.

Tissue samples will be obtained through noninvasive surgery, Von Hoff said. Then the patients will go home to await sequencing results that should be produced within a few weeks.

The idea is to then direct them to appropriate treatment, but Von Hoff declined to predict in how many cases that will be possible. “We don’t know,” Von Hoff said. “We do know there are more and more drugs out there for patients who have mutations.”
There have been other studies that sequenced disease tumors, most notably an ongoing government effort known as the Cancer Genome Atlas that aims to produce comprehensive genetic maps of at least 20 types of cancer.

What separates the new study is its attempt use the data to drive treatment strategies, not merely to collect information “It’s a different question,” the genomics institute’s Trent said. “This is a study about how we’re going to start to use this in a precision medicine approach.”

A big effort will go into “bioinformatic” analysis, which Von Hoff said will involve a trillion pieces of data per patient. Hoang said one project in lung cancer found 30,000 mutations.

In coming years, scientists expect the cost of sequencing to decline and the sophistication of the tools to improve to the point that sequencing becomes more viable as a diagnostic device.

Hoang said Life Technologies expects the cost of the reagent chemicals that it sells, which enable genome sequencing, to drop from $6,000 to $3,000 by the end of the year. “This is really laying the foundation for a future that may take five or 10 years to materialize,” Hoang said. “But it is truly groundbreaking.”

When to Consider prophylactic bilateral mastectomy...
Contralateral Prophylactic Mastectomy Associated With Survival in Select Breast Cancer Patients
ScienceDaily (Mar. 3, 2010) — Contralateral prophylactic mastectomy (CPM), a preventive procedure to remove the unaffected breast in patients with disease in one breast, may only offer a survival benefit to breast cancer patients age 50 and younger, who have early-stage disease and are estrogen receptor (ER) negative, according to researchers at The University of Texas M. D. Anderson Cancer Center.

Published online February 25 in the Journal of the National Cancer Institute, it's the first population-based study to find an association between the procedure and survival in any group of breast cancer patients. The findings should offer evidence to both the women making this often agonizing decision and the physicians responsible for their care.

According to Isabelle Bedrosian, M.D., assistant professor in M. D. Anderson's Department of Surgical Oncology, a growing number of breast cancer patients are opting for the procedure; recent statistics have shown that the rate of CPM in women with stage I-III breast cancer increased by 150 percent from 1998 to 2003 in the United States.

"In our clinic, we've seen a dramatic increase in the number of women requesting CPM, and across the breast cancer community, studies have shown that the utilization of the procedure is skyrocketing," said Bedrosian, the study's co-corresponding author. "Until now, we've counseled these patients on a very important, personal decision in a vacuum. With our study, our goal was to understand the implications of the surgery and who may benefit."

For the retrospective, population-based study, the researchers used the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) registry, the premier population-based cancer registry now representing 26 percent of the country's population, to identify 107,106 breast cancer patients who underwent a mastectomy for treatment, as well as a subset of 8,902 women who had CPM. All of the women were treated for stages I -- III breast cancer between 1998 and 2003. Patients were stratified for ER status, stage of disease and age. Breast cancer-specific survival served as the study's primary endpoint.

Rigorous analysis was paramount in the design of the study, said George J. Chang, M.D., assistant professor in M. D. Anderson's Department of Surgical Oncology.

"It was important to take a critical eye and look at all the different ways the data could be misinterpreted to ensure that biases were not impacting our findings," said Chang, the study's co-corresponding author. "Using multi-variable analysis as well as risk stratification, we did our analysis in many different ways -- through SEER, comparing the survival of these patients to that of the general population, as well as examining non-cancer related versus cancer-specific survival. All alternative analyses resulted in the same conclusion; we found one group for whom this surgery offers a true survival benefit."

The researchers found a clear survival benefit for a select group of women that represents less than 10 percent of the breast cancer population. Those younger than age 50 with stage I or II cancer with ER negative disease had a survival benefit of 4.8 percent at five years. However, both Bedrosian and Chang expect that future research will show increased survival benefit with longer follow-up in the population, as a patient's likelihood of getting a second breast cancer increases with time.

While the findings should serve as a guideline for breast cancer patients and their physicians to have an informed, medically-based discussion about CPM, they do not determine that CPM is medically inappropriate for all others with the disease, said the researchers.

"Our research found that breast cancer patients over the age of 60 can be reassured that they will not benefit from CPM," said Bedrosian. "However, there are other populations -- such as women between the age of 50 and 60 -- where the findings about the procedure remain less clear. In addition, for young women with early stage, estrogen receptive positive breast cancer who receive Tamoxifen for only five years, we really do not know whether they would derive a life-long protective effective from a second breast cancer event. Therefore, for some additional breast cancer patients, CPM may very well be a medically-appropriate option."

In addition, the researchers note, the study captured neither family history nor BRCA status; it also did not include DCIS, or stage 0 breast cancer patients.

In addition to Bedrosian and Chang, Chung Yuan Hu in the Department of Surgical Oncology, also authored the all-M. D. Anderson study.

Pomegranate Therapy...

Natural Compounds in Pomegranates May Prevent Growth of Hormone-Dependent Breast Cancer
ScienceDaily (Jan. 6, 2010) — Eating fruit, such as pomegranates, that contain anti-aromatase phytochemicals reduces the incidence of hormone-dependent breast cancer, according to results of a study published in the January issue of Cancer Prevention Research, a journal of the American Association for Cancer Research.
Pomegranate is enriched in a series of compounds known as ellagitannins that, as shown in this study, appear to be responsible for the anti-proliferative effect of the pomegranate.

"Phytochemicals suppress estrogen production that prevents the proliferation of breast cancer cells and the growth of estrogen-responsive tumors," said principal investigator Shiuan Chen, Ph.D., director of the Division of Tumor Cell Biology and co-leader of the Breast Cancer Research Program at City of Hope in Duarte, Calif.

Previous research has shown that pomegranate juice -- punica granatum L -- is high in antioxidant activity, which is generally attributed to the fruit's high polyphenol content. Ellagic acid found in pomegranates inhibits aromatase, an enzyme that converts androgen to estrogen. Aromatase plays a key role in breast carcinogenesis; therefore, the growth of breast cancer is inhibited.

Chen, along with Lynn Adams, Ph.D., a research fellow at Beckman Research Institute of City of Hope, and colleagues, evaluated whether phytochemicals in pomegranates can suppress aromatase and ultimately inhibit cancer growth.

After screening and examining a panel of 10 ellagitannin-derived compounds in pomegranates, the investigators found that those compounds have the potential to prevent estrogen-responsive breast cancers. Urolithin B, which is a metabolite produced from ellagic acid and related compounds, significantly inhibited cell growth.

"We were surprised by our findings," said Chen. "We previously found other fruits, such as grapes, to be capable of the inhibition of aromatase. But, phytochemicals in pomegranates and in grapes are different."

According to Gary Stoner, Ph.D., professor in the Department of Internal Medicine at Ohio State University, additional studies will be needed to confirm the chemopreventive action of Urolithin B against hormone-dependent breast cancer.

"This is an in vitro study in which relatively high levels of ellagitannin compounds were required to demonstrate an anti-proliferative effect on cultured breast cancer cells," said Stoner, who is not associated with this study. "It's not clear that these levels could be achieved in animals or in humans because the ellagitannins are not well absorbed into blood when provided in the diet."
Stoner believes these results are promising enough to suggest that more experiments with pomegranate in animals and humans are warranted.

Powel Brown, M.D., Ph.D., medical oncologist and chairman of the Clinical Cancer Prevention Department at the University of Texas M. D. Anderson Cancer Center, agreed with Stoner's sentiments and said these results are intriguing. He recommended that future studies focus on testing pomegranate juice for its effect on estrogen levels, menopausal symptoms, breast density or even as a cancer preventive agent.

"More research on the individual components and the combination of chemicals is needed to understand the potential risks and benefits of using pomegranate juice or isolated compounds for a health benefit or for cancer prevention," Brown said. "This study does suggest that studies of the ellagitannins from pomegranates should be continued."

Until then, Stoner said people "might consider consuming more pomegranates to protect against cancer development in the breast and perhaps in other tissues and organs."


Trial Launched to Test New Treatment for Pre-Invasive Breast Cancer
ScienceDaily (Mar. 2, 2010) — Can a drug that has been used to treat malaria for years possibly be used to treat breast cancer before it becomes invasive? That's what researchers at George Mason University's Center for Applied Proteomics and Molecular Medicine (CAPMM) and Inova Breast Care Institute (IBCI) are trying to prove.

In January, the IBCI and CAPMM launched the PINC Trial, short for Preventing Invasive Breast Neoplasia with Chloroquine. This three-year clinical trial will test the effectiveness of the anti-malarial drug chloroquine in treating 90 women with ductal carcinoma in situ (DCIS), a type of breast cancer in which the cancer cells start in the milk ducts but have not yet become invasive and spread in the breast. Once the cancer cells start to spread in the breast and throughout the body, the condition is considered invasive and can often be fatal.

With an estimated 254,650 patients diagnosed in 2009 alone, breast cancer is the most common form of cancer in women according to statistics by the American Cancer Society. Approximately one quarter of those patients will have DCIS. Many more women are being diagnosed with DCIS, non-invasive breast cancer, with the routine use of screening mammography.

According to Kirsten Edmiston, MD, the trial's principal investigator and medical director of cancer services at Inova Health System, the trial is designed to prevent breast cancer cells from becoming deadly by killing pre-invasive cancer cells using a novel therapy with chloroquine, which has been used to treat malaria in the past.

"We have identified a particular cellular process called autophagy that is very involved in the survival of DCIS. In pre-clinical work, our team found that if we block autophagy in DCIS cells with chloroquine, that it kills the cells so that they're not able to become invasive," says Edmiston. "What this trial is proposing is to treat DCIS patients with chloroquine, an autophagy blocker before they receive standard of care surgery to treat their DCIS disease. We believe that the treatment will kill the DCIS cells before they become invasive and shrink the size of the DCIS. We may be able to prevent someone from needing a mastectomy and offer them breast conserving surgery."

Once patients have consented and enrolled, the size of their breast tumor will be measured through a non-invasive imaging technique called magnetic resonance imaging (MRI). Tissue samples will be taken from patients by Inova's doctors and transported to CAPMM for analysis. The PINC trial will combine chloroquine with Tamoxifen depending on the patient's tumor profile. After treatment, the MRI will be repeated to see if the tumor has shrunk and the patient will then proceed with surgery and follow up therapy.

What made the researchers think to use a malaria drug to treat breast cancer? According to Ginny Espina, a CAPMM research assistant professor, it works by starving the cancerous cells.

"Pre-cancerous cells have adapted to survive inside the milk duct without a blood supply and with very few nutrients. They overcome starvation through a process called autophagy. It's a way for a cell to make its own food and store it in a 'cookie jar.' In the breast ducts, the DCIS cells use these 'cookies' to survive and potentially spread. Simply put, chloroquine goes into the cell's 'cookie jars' and prevents the cells from using that food so that they eventually die from starvation," says Espina.

Of note, researchers are also using chloroquine in patients with unique types of brain tumors.

The treatment of DCIS is controversial because most DCIS lesions remain dormant and do not become invasive. Physicians do not want to over treat DCIS and cause unnecessary side effects if the DCIS does not become aggressive. However, chloroquine is a relatively safe treatment that does not have the severe side effects of typical chemotherapy.

"I think the most exciting thing is that we are able to offer women a new clinical trial using a well tolerated therapy in a new way to help prevent the development of invasive breast cancer and hopefully, ultimately, it will keep them from needing any additional treatment or surgery," says Edmiston. "We look forward to a future where all breast cancer can be prevented or destroyed."

The clinical study is being funded by George Mason University and Inova Health System. This study is based on scientific findings made under a Department of Defense funded breast cancer grant to George Mason University (Lance Liotta MD, PhD) in partnership with Inova.

Her2 News...
Neoadjuvant Chemotherapy With Trastuzumab Followed by Adjuvant Trastuzumab Versus Neoadjuvant Chemotherapy Alone, in Patients With HER2-Positive Locally Advanced Breast Cancer (the NOAH Trial)

Lancet. 2010 Jan 30;375(9712):377-384, L Gianni, W Eiermann, V Semiglazov, A Manikhas, A Lluch, S Tjulandin, M Zambetti, F Vazquez, M Byakhow, M Lichinitser, MA Climent, E Ciruelos, B Ojeda, M Mansutti, A Bozhok, R Baronio, A Feyereislova, C Barton, P Valagussa, J Baselga

Addition of neoadjuvant and adjuvant trastuzumab to neoadjuvant chemotherapy improved event-free survival and tumor response rates in women with HER2-positive locally advanced or inflammatory breast cancer

Supplementary editorial provided by OncologySTAT
Addition of neoadjuvant and adjuvant trastuzumab to neoadjuvant chemotherapy improved event-free survival and tumor response rates in women with HER2-positive locally advanced or inflammatory breast cancer.

Lee Schwartzberg, MD, Editor-in-Chief Oncology Stat
In HER2-positive breast cancer, adding trastuzumab to chemotherapy yields impressive benefit in both the adjuvant and metastatic setting and is the standard of care. The current trial fills in the gaps by providing randomized clinical trial evidence of a 41% improvement in event-free survival when trastuzumab was given to patients with HER2-positive locally advanced or inflammatory breast cancer in the neoadjuvant setting. Particularly noteworthy in this NOAH trial was the use of every-3-weeks dosing of trastuzumab from initiation of treatment, a low cardiac event rate despite concurrent adriamycin/trastuzumab therapy, and a marked benefit recorded in the inflammatory breast cancer group of a 73% improvement in event-free survival.

Background: The monoclonal antibody trastuzumab has survival benefit when given with chemotherapy to patients with early, operable, and metastatic breast cancer that has HER2 (also known as ERBB2) overexpression or amplification. We aimed to assess event-free survival in patients with HER2-positive locally advanced or inflammatory breast cancer receiving neoadjuvant chemotherapy with or without 1 year of trastuzumab.

We compared 1 year of treatment with trastuzumab (given as neoadjuvant and adjuvant treatment; n=117) with no trastuzumab (118), in women with HER2-positive locally advanced or inflammatory breast cancer treated with a neoadjuvant chemotherapy regimen consisting of doxorubicin, paclitaxel, cyclophosphamide, methotrexate, and fluorouracil. Randomisation was done with a computer program and minimisation technique, taking account of geographical area, disease stage, and hormone receptor status. Investigators were informed of treatment allocation. A parallel cohort of 99 patients with HER2-negative disease was included and treated with the same chemotherapy regimen. Primary endpoint was event-free survival. Analysis was by intention to treat. This study is registered, number ISRCTN86043495.

Trastuzumab significantly improved event-free survival in patients with HER2-positive breast cancer (3-year event-free survival, 71% [95% CI 61–78; n=36 events] with trastuzumab, vs 56% [46–65; n=51 events] without; hazard ratio 0•59 [95% CI 0•38–0•90]; p=0•013). Trastuzumab was well tolerated and, despite concurrent administration with doxorubicin, only two patients (2%) developed symptomatic cardiac failure. Both responded to cardiac drugs.

The addition of neoadjuvant and adjuvant trastuzumab to neoadjuvant chemotherapy should be considered for women with HER2-positive locally advanced or inflammatory breast cancer to improve event-free survival, survival, and clinical and pathological tumour responses.

Copyright © Elsevier Inc. All rights reserved

PARP Props...

PARP Inhibition Could Have Broad Application
Elsevier Global Medical News February 2010

Lee Schwartzberg is Senior Partner and Medical Director, The West Clinic, Memphis, TN. 
1. In your view, which development in breast cancer that has occurred in 2009 could have the most significant impact on oncology?
The development in 2009 with the potential for the most impact was the emergence of poly(ADP-ribose) polymerase (PARP) inhibitors as a new class of agent for the treatment of malignancies. Reports this year confirmed both single-agent activity of PARP inhibitors and synergy with chemotherapy. Moreover, the benefit was highly significant, leading to better overall survival in one small randomized trial.

2. What specific changes in oncology have you observed or do you foresee as a result of this development?

If results hold up, PARP inhibition will be the first systemic therapy designed for hereditary cancers that contain a somatic mutation responsible for the malignancy, specifically BRCA1 or BRCA2 mutations. Patients with these mutations lack functional BRCA proteins, which are important in normal DNA repair, and thus they develop cancers. More broadly, there is exciting evidence of benefit from PARP inhibition in triple-negative breast cancer, an aggressive subtype for which there is currently no specific therapy.

3. Could you put this development into historical perspective for the practicing oncologist?

While PARP enzymatic function as a DNA repair mechanism has been recognized for some time, what is new is the idea that inhibition of this pathway in cells where alternative repair systems (such as BRCA) have already been damaged could lead to cancer cell death. This concept is termed synthetic lethality. This could represent a paradigm shift leading to exploration of similar approaches in other critical cellular pathways.

4. Would you sum up in a single sentence why you chose this development as the top story of the past year?

PARP inhibition capitalizes on a central and critical function of malignant tissue, DNA repair, and has already shown strong evidence of benefit. This class of drugs could have broad application in treating other cancers as well.
1. O'Shaughnessy J, Osborne C, Pippen J, et al. Final results of a randomized phase II study demonstrating efficacy and safety of BSI-201, a Poly (ADP-ribose) polymerase (PARP) inhibitor, in combination with gemcitabine/carboplatin (G/C)in metastatic triple-negative breast cancer (TNBC) (abstract 3122). Presented at 32nd San Antonio Breast Cancer Symposium 2009; San Antonio, TX; December 10-13, 2009. 


It's not you, it the treatment...
Decline in Breast Cancer Mortality Means Increase in Chronic Symptoms
Elsevier Global Medical News. 2008 Jan 17, B. Jancin

SAN ANTONIO (EGMN) - The other side of the impressive decline in breast cancer mortality during the last several decades is the unprecedented number of survivors with tough to control chronic symptoms caused by the disease or its aggressive therapy, Dr. Charles L. Loprinzi said at the San Antonio Breast Cancer Symposium. 

He focused on evidence-based therapies of five of the most common and problematic breast cancer survivorship issues: vaginal dryness, fatigue, chemotherapy-induced neuropathy, diminished libido, and hot flashes.

Vaginal dryness: Pilocarpine shows enough promise that Dr. Loprinzi and colleagues have embarked on an ongoing randomized, double-blind, placebo-controlled trial of the oral drug at 5 mg once daily or b.i.d. in 192 women treated for breast cancer. Results should be available next year.

The impetus for the study was an anecdotal report a few years ago of marked clinical improvement in cyclophosphamide-induced vaginal dryness in four patients, along with a separate earlier report of significantly decreased vaginal dryness as a secondary outcome measure in a phase III trial of pilocarpine for oral and ocular dryness in patients with Sjögren's syndrome (Arch. Intern. Med. 1999;159:174-81). The drug is approved for that indication as well as for dry mouth caused by head and neck radiation therapy.

Estrogen therapy is effective for vaginal dryness and is worthwhile in some severely affected women, but there is concern that it could promote breast cancer recurrence. That concern extends to vaginal estrogens as well.

"All of the vaginal agents, in my mind, do lead to systemic levels of estrogen in some patients," said Dr. Loprinzi, professor of medicine and chair of oncology at the Mayo Clinic, Rochester, Minnesota.

Nonestrogenic vaginal lubricants are "somewhat effective," but are clearly inferior to estrogen in comparative studies, he added.

Fatigue: This is a major complaint for cancer patients across the full spectrum of disease, from those on adjuvant chemotherapy to patients with advanced, incurable cancer. Exercise is the intervention with the strongest evidence base.

"Exercise is the answer, not more rest," Dr. Loprinzi emphasized.

Modafinil, donepezil, L-carnitine, and methylphenidate have been looked at in pilot studies, but more work is needed before any of them can be recommended for cancer-related fatigue. 

Similarly, Dr. Loprinzi and coworkers were encouraged by the results of their pilot 8-week, double-blind dose-finding study of American ginseng, in which roughly 25% of cancer patients on 1,000 or 2,000 mg/day of ginseng reported their fatigue was moderately to very much better, compared with 10% on placebo. 

"The evidence isn't there to recommend ginseng for use at this time, but we're excited about it. The toxicity profile looked very favorable. We're about to start a larger placebo-controlled trial," the oncologist said.

Chemotherapy-induced neuropathy: Gabapentin is widely prescribed for this problem. However, the sole rigorous study to date - a multicenter, placebo-controlled, double-blind, crossover trial conducted by Dr. Loprinzi and colleagues in the North Central Cancer Treatment Group (NCCTG) - failed to demonstrate any benefit (Cancer 2007 Nov. 1;110:2110-8).

Vitamin E (alpha-tocopherol) at a dose of 400 mg/day was reported to protect against cisplatin-induced peripheral neuropathy and ototoxicity in an interim analysis of a 50-patient randomized, placebo-controlled study presented at last year's American Society of Clinical Oncology meeting. The NCCTG has an ongoing randomized trial, also comparing vitamin E at 400 mg/day and placebo. Until the results are in, Dr. Loprinzi urged caution in using vitamin E for prevention of chemotherapy-induced neuropathy.

"We haven't proved that it's helpful, number 1, and also there are some data suggesting that vitamin E can get in the way of cytotoxic therapy, particularly radiation therapy for the head and neck area. Maybe that will also apply to chemotherapy. We need to sort all this out," he said.

Low libido: Sexual counseling is the only thing that can be recommended. Transdermal testosterone cream proved ineffective in a double-blind, randomized, placebo-controlled crossover trial conducted by Dr. Loprinzi and the NCCTG (J. Natl. Cancer Inst. 2007 May 2; 99:672-9).

Testosterone did improve low libido in several prior studies in women without cancer. The most likely explanation for the disparate results lies in the fact that all participants in those studies were either premenopausal or on estrogen replacement therapy; in contrast, the cancer patients weren't receiving estrogen, he noted.

Hot flashes: Effective nonhormonal therapies are available. Dr. Loprinzi and his colleagues showed in a randomized, double-blind, placebo-controlled trial that venlafaxine at 37.5 or 75 mg/day reduced hot flash scores by 40% and 60%, respectively, from baseline (Lancet 2000; 356:2059-63).

In a subsequent double-blind, placebo-controlled crossover trial, they demonstrated that fluoxetine at 20 mg/day also was effective in reducing hot flashes in women with a history of breast cancer (J. Clin. Oncol. 2002;20:1578-83), although it appears to be less so than venlafaxine.

Paroxetine at 20 mg/day appears to be roughly as effective as venlafaxine at reducing hot flashes, based upon randomized controlled studies by other investigators. Sertraline at 50 and 100 mg/day doesn't seem to work as well as do the other antidepressants.

A couple of negative venlafaxine studies have been reported. However, neither featured adequate pretreatment baseline hot flash scores. That's a fatal methodologic flaw, according to Dr. Loprinzi, who noted that in his study that venlafaxine reduced hot flash scores by an average of 30% on day 1, compared with the baseline week.

Tamoxifen is metabolized by cytochrome P450 2D6 to a key active metabolite, endoxifen, which is believed to be responsible for the selective estrogen receptor modulator's efficacy in preventing breast cancer. Coadministration of paroxetine and tamoxifen has been reported to result in a significant decrease in plasma endoxifen levels (J. Natl. Cancer Instit. 2003;95:1758-64). In contrast, venlafaxine didn't reduce endoxifen levels in another study (Clin. Pharmacol. Ther. 2006;80:61-74).

Another nonhormonal option is gabapentin, which at 900 mg/day, significantly reduced hot flash scores in a placebo-controlled trial by investigators at the University of Rochester (Obstet. Gynecol. 2003;101:337-45). 

Copyright © 2008 International Medical News Group

At last, they are coming to their senses...

New Mammogram Guidelines Issued ... Again Mon Jan 4, 3:16 pm ET

Breast cancer screening just got more confusing today, as two medical organizations announced annual mammograms should begin at age 40, and earlier for high-risk women. The recommendations contradict a recent advisory for less frequent screenings beginning at age 50, not 40.
The recommendations for less frequent mammograms, released in November, came from the U.S. Preventive Services Task Force, with panel experts saying they were responding to data showing routine mammograms starting at age 40 rarely saved lives and more often resulted in misdiagnoses that just fueled anxiety and debilitating treatment.
This new advice, which is published in the January issue of the Journal of the American College of Radiology, comes from the Society of Breast Imaging (SBI) and the American College of Radiology (ACR). And these groups suggest just the opposite - that the screening does save lives.
"The significant decrease in breast cancer mortality, which amounts to nearly 30 percent since 1990, is a major medical success and is due largely to earlier detection of breast cancer through mammography screening," said lead study author Dr. Carol H. Lee, a radiologist at Memorial Sloan-Kettering Cancer Center. "For women with the highest risk of developing breast cancer, screening technologies in addition to mammography have been adopted," said Lee, who is the chair of ACR's Breast Imaging Commission.
What's a woman to do? Regarding how women should follow the task force recommendations from November, Dr. Carl D'Orsi, director of Emory University's Breast Imaging Center, said, "As a bottom line, they should be ignored." D'Orsi was a member of the team that came out with today's recommendations.
Dr. Ned Calonge, chairman of the U.S. Preventive Services Task Force, had not responded to a request for an interview as of this writing.
Screening science
D'Orsi and his colleagues reviewed the results of several randomized trials in Europe and North America, which included nearly 500,000 women in total. The review of these studies showed a 26 percent reduction in breast cancer mortality.
"This is scientifically driven with data, unlike what the task force did," D'Orsi said.
While today's recommendations are consistent with those put out by other groups, including the American Cancer Society, the new ones include other imaging techniques in addition to mammography.
Here are some of the highlights:

  • The average patient should begin annual mammograms at age 40, and high-risk patients should begin by age 30 but not before 25. A woman with certain mutations to the BRCA1 or BRCA2 genes would be considered a high-risk individual.
  • Annual MRI (magnetic resonance imaging) starting by age 30 is recommended for carriers of deleterious BRCA mutations. Women who are considered to have at least a 20 percent lifetime risk for breast cancer based on family history should get annual mammograms and annual MRI starting at age 30 (not before age 25), or 10 years before the age of the youngest affected relative, whichever is later.
  • Ultrasound, in addition to mammography, can be considered for high-risk women and those with dense breast tissue. While ultrasound isn't as sensitive as MRI to detecting breast cancer, D'Orsi said some women can't get an MRI due to their weight (those over 300 pounds) and other factors.
Comparing recommendations
The U.S. Preventive Services Task Force, an independent government agency made up of 16 primary care physicians and public health specialists, in November recommended breast cancer screening every other year for women aged 50 to 74. They argued against routine screening before this age.
That was counter to their own guidelines from 2002, D'Orsi said.
"All of a sudden, with no new data - ignoring the fact that there are seven trials that demonstrate a drop in breast cancer mortality with use of mammography versus no mammography, plus that breast cancer mortality has dropped 30 percent - they come out with a recommendation that no screening be done at age 40 to 49," D'Orsi told LiveScience.
He added, "Basically they said nothing is good. Just wait until it breaks through your skin and we'll take care of it. That's what we did in 1940."
In fact, the task force did note a 15-percent reduction in mortality among those ages 40 to 49 who are screened," D'Orsi and colleagues wrote in their research paper. But they stated the harms outweigh the benefits. These harms include: anxiety over false positive results, the screening itself, need for additional testing or biopsy, and the possibility of overdiagnosis and overtreatment.
Why start screening at age 50? Essentially, years ago scientists began grouping women under and over age 50 into separate groups. And so when the age groups get compared, there are far fewer incidences of breast cancer in the younger group than in those 50 and older.
"Of course there's more breast cancer there, because it's age dependent," D'Orsi said. "That doesn't mean you don't screen. As a matter of fact those cancers [in the younger age group] are biologically more significant and may have a greater impact on life expectancy."

November, 2009
Government Panel Urges Change in Age from 40 to 50 for Mammograms-
A response

To save money, to reduce insurance costs and to reduce "Anxiety" a panel that guides the ACS has declared that women should skip mammograms until the age of 50, and then only have them every other year or so... because they don't do any good.... they cause too much anxiety....they cost too much.

Not having screening and having your cancer found too late costs a lot of money, too. It causes anxiety that is beyond all compare. And they can't do any good because your cancer is already spreading.

This blog post is dedicated to the women we have lost, only very few had the genetic cancer link that is exempt from this murderous recommendation. Most of these women were diagnosed before the age of 40 or in their early 40s.  None of them are alive today.
Kari Lynn
Mary Ellen

In Reversal, Panel Urges Mammograms at Age 50, not 40
By Gina Kolata

Most women should start regular breast cancer screening at age 50, not 40, according to new guidelines released Monday by an influential group that provides guidance to doctors, insurance companies and policy makers.

The new recommendations, which do not apply to a small group of women with unusual risk factors for breast cancer, reverse longstanding guidelines and are aimed at reducing harm from overtreatment, the group says. It also says women age 50 to 74 should have mammograms less frequently — every two years, rather than every year. And it said doctors should stop teaching women to examine their breasts on a regular basis.
Just seven years ago, the same group, the
United States Preventive Services Task Force, with different members, recommended that women have mammograms every one to two years starting at age 40. It found too little evidence to take a stand on breast self-examinations.
The task force is an independent panel of experts in prevention and primary care appointed by the federal
Department of Health and Human Services.

Its new guidelines, which are different from those of some professional and advocacy organizations, are published online in The
Annals of Internal Medicine They are likely to touch off yet another round of controversy over the benefits of screening for breast cancer.
Dr. Dianna Petitti vice chairwoman of the task force and a professor of biomedical informatics at Arizona State University said the guidelines were based on new data and analyses and were aimed at reducing the potential harm from overscreening.

While many women do not think a screening test can be harmful, medical experts say the risks are real. A test can trigger unnecessary further tests, like biopsies, that can create extreme anxiety. And mammograms can find cancers that grow so slowly that they never would be noticed in a woman’s lifetime, resulting in unnecessary treatment.

Over all, the report says, the modest benefit of mammograms — reducing the breast cancer death rate by 15 percent — must be weighed against the harms. And those harms loom larger for women in their 40s, who are 60 percent more likely to experience them than women 50 and older but are less likely to have breast cancer, skewing the risk-benefit equation. The task force concluded that one cancer death is prevented for every 1,904 women age 40 to 49 who are screened for 10 years, compared with one death for every 1,339 women age 50 to 74, and one death for every 377 women age 60 to 69.

The guidelines are not meant for women at increased risk for breast cancer because they have a gene mutation that makes the cancer more likely or because they had extensive chest radiation. The task force said there was not enough information to know whether those women would be helped by more frequent mammograms or by having the test in their 40s. Other experts said women with close relatives with breast cancer were also at high risk.

Dr. Petitti said she knew the new guidelines would be a shock for many women, but, she said, “we have to say what we see based on the science and the data.”
The National Cancer Institute said Monday that it was re-evaluating its guidelines in light of the task force’s report.
But the American Cancer Society and the American College of Radiology both said they were staying with their guidelines advising annual mammograms starting at age 40.
The cancer society, in a
statement by Dr. Otis W. Brawley, its chief medical officer, agreed that mammography had risks as well as benefits but, he said, the society’s experts had looked at “virtually all” the task force and additional data and concluded that the benefits of annual mammograms starting at age 40 outweighed the risks.
Other advocacy groups, like the National Breast Cancer Coalition, Breast Cancer Action, and the National Women’s Health Network, welcomed the new guidelines.
“This is our opportunity to look beyond emotions,” said Fran Visco, president of the National Breast Cancer Coalition. The task force “is an independent body of experts that took an objective look at the data,” Ms. Visco said. “These are the people we should be listening to when it comes to public health messages.”
Some women, though, were not pleased. “I know so many people who had breast cancer and survived, and what saved their lives was early detection,” Janet Doughty, 44, of San Clemente, Calif., said in a telephone interview. She said she had had an annual mammograms since her late 30s and would not stop now.
The guidelines are not expected to have an immediate effect on insurance coverage but should make health plans less likely to aggressively prompt women in their 40s to have mammograms and older women to have the test annually.
Congress requires Medicare to pay for annual mammograms. Medicare can change its rules to pay for less frequent tests if federal officials direct it to.
Private insurers are required by law in every state except Utah to pay for mammograms for women in their 40s.
But the new guidelines are expected to alter the grading system for health plans, which are used as a marketing tool. Grades are issued by the
National Committee for Quality Assurance, a private nonprofit organization, and one measure is the percentage of patients getting mammograms every one to two years starting at age 40.
That will change, said Margaret E. O’Kane, the group’s president, who said it would start grading plans on the number of women over 50 getting mammograms every two years.
The message for most women, said
Dr. Karla Kerlikowske, a professor in the department of medicine, epidemiology and biostatistics at the University of California, San Francisco, is to forgo routine mammograms if they are in their 40s.
Starting at age 50, Dr. Kerlikowske said, “the message is to get 10 mammograms in a lifetime, one every two years.” That way they get the most benefit and the least harm from the test. If women are healthy, she added, they might consider having mammograms every two years until age 74.
Nearly two-thirds of all women in their 40s had mammograms within the last two years, as did 72 percent of women age 50 to 65, according to an editorial by Dr. Kerlikowske that accompanies the report.
In order to formulate its guidelines, the task force used new data from mammography studies in England and Sweden and also commissioned six groups to make statistical models to analyze the aggregate data. The models were the only way to answer questions like how much extra benefit do women get if they are screened every year, said
Donald A. Berry, a statistician at the University of Texas M. D. Anderson Cancer Center and head of one of the modeling groups.
“We said, essentially with one voice, very little,” Dr. Berry said. “So little as to make the harms of additional screening come screaming to the top.”
The harms are nearly cut in half when women have mammograms every other year instead of every year. But the benefits are almost unchanged.
The last time the task force issued guidelines for mammograms, in 2002,
the report was announced by Tommy G. Thompson, the secretary of health and human services. When the group recommended mammograms for women in their 40s, some charged the report was politically motivated. But Dr. Alfred Berg of the University of Washington, who was the task force chairman at the time, said “there was absolutely zero political influence on what the task force did.”
It was still a tough call to make, Dr. Berg said, adding that “we pointed out that the benefit will be quite small.” In fact, he added, even though mammograms are of greater benefit to older women, they still prevent only a small fraction of breast cancer deaths.
Different women will weigh the harms and benefits differently, Dr. Berg noted, but added that even for women 50 and older, “it would be perfectly rational for a woman to decide she didn’t want to do it.”
Researchers worry the new report will be interpreted as a political effort by the Obama administration to save money on health care costs.

Of course, Dr. Berry noted, if the new guidelines are followed, billions of dollars will be saved.
“But the money was buying something of net negative value,” he said. “This decision is a no-brainer. The economy benefits, but women are the major beneficiaries.”

Scientists have found a faulty gene linked to half of all breast cancers which experts have hailed as the most important discovery in the disease since the 1970s.
 Rebecca Smith, Medical Editor Published: 11:39AM BST 05 Oct 2009

The finding will help researchers understand how cancer develops and may in future lead to new treatments, they said.
Everyone is born with the gene, called NRG1, but in some people it gets damaged during their lifetime and this can lead to cancer developing, it has been found.
Damaged NRG1s have been found in half of breast cancers and it has also been implicated in half of all prostate and bowel cancers along with one quarter of ovarian and bladder cancers.
When the gene works properly it acts as a brake, stopping cancer cells from growing, but when it is damaged the brakes are off, allowing the cells to multiply into a tumour.
Everybody is born with an intact NRG1 but it gets damaged in some people during their lifetime, thereby enabling cancer to develop.
The exact reason why the gene is damaged is lost has not yet been discovered.
However, by identifying the gene, experts hope they will be able to target therapies at specific cancers in the future.
The discovery of NRG1 is the most significant step forward in cancer gene research since another gene, p53, was discovered in the 1970s and was later implicated in the development in cancer in the 1980s.
This was the first "tumour suppressor" gene found within cells and it is now known that p53 is faulty or inactivated in many cancers.
The discovery was described as a "major step forward" by cancer charities in working out how cancer develops.
Dr Paul Edwards, of the department of pathology at the University of Cambridge, who discovered the gene with colleagues, said it provided "vital information" about how some cancers spread.
He said: "I believe NRG1 could be the most important tumour suppressor gene discovery in the last 20 years as it gives us vital information about a new mechanism that causes breast cancer.
"We found the gene on chromosome 8 partly by good luck and partly by good judgment.
"In every case that we looked at where a big chunk of chromosome 8 had been lost, at least part of the gene was lost.
"The gene was effectively 'turned off' in a lot of breast cancers.
"If we have found the gene that is lost on chromosome 8 and we know that some other cancers also lose that bit of chromosome 8, then it is logical that it is the same gene.
"We have got strong evidence that the gene is implicated in breast cancer but we have no reason to think it's not the same for other cancers, including prostate and colon cancer."
The research was published in the journal Oncogene and funded by Breast Cancer Campaign and Cancer Research UK.
Arlene Wilkie, director of research and policy at Breast Cancer Campaign, said: "Knowing the identity of this gene will lead to far more detailed studies of how it works and how it is involved in breast cancer development.
"This research is a major step forward in understanding the genetics of cancer and could open up a host of new strategies to improve diagnosis and treatment.
"In the UK, 12,000 women die from this disease every year, so it is vital we understand how breast cancer develops in order to stop it happening."
Lesley Walker, director of cancer information at Cancer Research UK, said: "This discovery is an important step forward in understanding a disease that more than 45,500 women are diagnosed with in the UK each year.
"It might then be possible to develop ways to bypass the gene or target treatments to the defect."

Aromatase Inhibitors and Joint Pain: A Deeper Look
Nick Mulcahy
September 23, 2009 — One third of postmenopausal women with breast cancer taking aromatase inhibitors (AIs) reported arthralgia — either new onset or worsening, according to investigators of a new study published online September 14 in the Journal of Clinical Oncology.
This percentage of patients experiencing joint pain was "expected," according to an editorial accompanying the study.
However, the study authors did not stop at investigating the prevalence of AI-associated arthralgia.
Because "few studies" have investigated the morphologic changes in joints and tendons in patients with this pain, the study authors used sonographic and electrophysiologic measurements to take a look at the affected tissues.
Nevertheless, the new study does not authoritatively correlate the findings from sonography and electromyography with clinical findings, observes the editorialist, Rowan T. Chlebowski, MD, PhD, from the Los Angeles BioMedical Research Institute at Harbor UCLA Medical Center in Torrance, California.
For instance, patients in the study with AI-related arthralgia had more frequent electrophysiologic findings of carpal tunnel syndrome (46% vs 20%; P < .05) than those without arthralgia (including those taking and those not taking AIs).
However, this 49% incidence of carpal tunnel syndrome in patients with AI-associated arthralgia is much higher than when the syndrome is identified through clinical symptoms. In large clinical trials of AIs and tamoxifen, the incidence of carpel tunnel syndrome was less than 3% for patients taking the AIs, Dr. Chlebowski notes.
The authors of the new study acknowledge that "the real prevalence of carpel tunnel syndrome would have been different if the signs and symptoms [had] been taken into consideration."
Very few patients discontinue treatment because of arthralgia.
AI-associated arthralgia is a "substantial problem" and one in need of "improved interventions," Dr. Chlebowski writes.
However, the editorialist and the study authors agree that most joint pain associated with AIs is mild to moderate and is best managed with analgesics. "Very few patients discontinue treatment because of arthralgia," the authors note.
More Findings
In the study, 120 postmenopausal patients with stage I to III breast cancer were evaluated for anatomic changes in the joints, and inflammatory markers were compared by Turkish investigators, led by Omer Dizdar, MD, from Hacettepe University Institute of Oncology in Ankara.
The team found that a range of markers of inflammation, such as C-reactive protein, were comparable in the patients taking AIs and the control subjects, and in the study participants with and without arthralgia.
The study supports previous reports that autoimmune disease "does not play a role in the etiology of AI-associated arthralgias," observes Dr. Chlebowski.
With regard to anatomic changes, the investigators found that the patients often had changes in their affected joints and tendons. Women taking AIs (n = 92) had increased tendon thicknesses, which is associated with the syndrome, compared with a control group of women (n = 28) with breast cancer not receiving the therapy (P < .01). Patients with AI-related arthralgia had more frequent joint and tendon effusions than those without pain (69% vs 42%; P < .05).
"These findings suggest that increased tendon thicknesses in patients on AIs may reflect some form of tendinopathy secondary to AI use. Further damage to the tendons and synovium results in effusions in tendon sheaths in a subgroup of patients, which is translated as arthralgia clinically," the authors write.
Anatomical matters aside, both Dr. Chlebowski and the study authors believe that arthralgia in this setting is also related to hormonal factors to some degree. Both note that joint pain is also a problem in postmenopausal women, even without breast cancer. In the landmark Women's Health Initiative (WHI) study, 74% of women without breast cancer reported joint pain, writes Dr. Chlebowski.
Notes on Managing Arthralgias
This study does not change the basic approach of clinicians to arthralgia, says Dr. Chlebowski.
At present, oncologists should carefully observe their patients for development of this problem.
"At present, oncologists should carefully observe their patients for development of this problem, clearly express to their patients the benefits of continued adherence [to AIs], and provide the limited available therapies," he writes.
The limited therapies can include acupuncture; 1 small pilot study suggested benefit from a 6-week regimen, notes Dr. Chlebowski. Vitamin D supplementation is a question "considered open," he adds, explaining that 2 ongoing studies are evaluating high-dose supplementation for AI-associated joint pain. However, 2 other trials, including the WHI, did not show any benefit from the vitamin, he says.
Joint pain associated with AIs still does not have an "optimal management strategy," writes Dr. Chlebowski.
Nevertheless, he cites a recent expert panel's recommendation to use "high-dose nonsteroidal anti-inflammatory drugs or selective COX-2 inhibitors as initial short-term therapy . . . to address initial pain relief, with subsequent titration to minimum effective dosage" (Ann Rheum Dis. 2007; 66:377-388).
Dr. Chlebowski reports being a consultant to AstraZeneca, Novartis, and Pfizer, all of which market AIs, and receiving honoraria from AstraZeneca and Novartis. The study authors have disclosed no relevant financial relationships.
J Clin Oncol. Published online before print September 14, 2009. Abstract, Abstract

Metformin is more effective than chemotherapy alone - Study supports cancer stem cells hypothesis

In a one-two punch, a familiar diabetes drug reduced tumors faster and prolonged remission in mice longer than chemotherapy alone by targeting cancer stem cells, Harvard Medical School researchers reported in the September 14 online first edition of Cancer Research, a journal of the American Association for Cancer Research.

"We have found a compound selective for cancer stem cells" said lead researcher Kevin Struhl, Ph.D ., the David Wesley Gaiser professor of biological chemistry and molecular pharmacology at Harvard Medical School. "What’s different is that ours is a first-line diabetes drug"

These findings add to a growing body of preliminary evidence in cells, mice and people that metformin may improve breast cancer outcomes in people. In this study, the diabetes drug seemed to work independently of its ability to improve insulin sensitivity and lower blood sugar and insulin levels, all of which are also associated with better breast cancer outcomes.

The results fit within the cancer stem cell hypothesis, an intensely studied idea that small subsets of cancer cells have a special power to initiate tumors, fuel tumor growth and promote recurrence of cancer. Cancer stem cells appear to resist conventional chemotherapies, which kill the bulk of the tumor.

"There is a big desire to find drugs specific to cancer stem cells" said Struhl. "The cancer stem cell hypothesis says you cannot cure cancer unless you also get rid of the cancer stem cells. From a purely practical point of view, this could be tested in humans. It’s already [in use as] a first-line diabetes drug"

The possible usefulness of a diabetes drug against cancer lends credence to an emerging idea that, in the vast and complex alphabet soup of molecular interactions within cells, a relatively few biological pathways will turn out to be most important for many different diseases, Struhl suggested.

In experiments led by postdoctoral fellows Heather Hirsch, Ph.D ., and Dimitrios Iliopoulos, Ph.D ., the combination of metformin and the cancer drug doxorubicin killed human cancer stem cells and non-stem cancer cells in culture. The researchers used four genetically distinct breast cancer cell lines.

In mice, pretreatment with metformin prevented the otherwise dramatic ability of human breast cancer stem cells to form tumors. In other mice where tumors took hold for 10 days, the combination therapy also reduced tumor mass more quickly and prevented relapse for longer than doxorubicin alone. In the two months between the end of treatment and the end of the experiment, tumors regrew in the mice treated with chemotherapy alone, but not in those who received both drugs. Metformin was ineffective in treating tumors when used alone.

"This is an exciting study" said Jennifer Ligibel, M.D ., a medical oncologist at the Dana-Farber Cancer Institute and a Harvard Medical School instructor in medicine. Ligibel and colleagues at the National Cancer Institute of Canada Clinical Trials Group are developing a large-scale phase II trial and will study its metformin’s impact on recurrence in women treated for early stage breast cancer.

"There is a lot of interest in studying metformin in breast cancer, but so far we do not have direct evidence that metformin will improve outcomes in patients" said Ligibel, who was not involved in the current study "That’s what this trial is for"

So far, observational studies have suggested a lower risk of cancers, including breast cancer, and better response to chemotherapy in patients with diabetes who are treated with metformin, she said. Results of basic science studies have also suggested plausible biological mechanisms. The study from the Struhl lab suggests a potential new pathway through which metformin could have an effect on breast cancer cells, according to Ligibel.

In their search for compounds that selectively destroy cancer stem cells, researchers hope to improve cancer outcomes. But the story is never as simple in human cancers, according to Kornelia Polyak, M.D ., Ph.D ., a breast cancer researcher at the Dana-Farber Cancer Institute and an associate professor of medicine at Harvard Medical School.

Cancer stem cells are a shifty target, said Polyak, who was not involved in the current study. For example, any cancer cell can acquire the properties of a cancer stem cell, and cancer stem cells can change into non-stem cancer cells, which can be just as deadly. Clinical trials in people are needed to test these ideas, according to Polyak.

The study by Struhl and colleagues is an offshoot of a larger project in his lab to systematically track how gene activity changes when cells transform into cancer. These changes were remarkably similar to gene dynamics in diabetes and other inflammatory conditions.

The researchers reasoned that if a common genetic pathway underlies different diseases, drugs that work against one disease might work against another. In a screen, the most effective drug inhibiting the transformation of cells into cancer was metformin, which led to the experiments in this study. They were further encouraged by the low dose of metformin needed for the effect in the laboratory, compared to the amount needed for analogous molecular experiments in basic diabetes research. The relative dosage for treating or preventing cancer is unknown and untested in people.

Struhl and Harvard Medical School have applied for a patent for a combined therapy of metformin and a lower dose of chemotherapy, which is being tested in animals. The National Institutes of Health and the American Cancer Society funded this research.

News Briefing: The American Association for Cancer Research will host a news briefing about the results of this study, which is published online first in Cancer Research.

Date: Monday, Sept. 14, 2009
Time: 10:00 a.m. ET

Moderator - Frank Rauscher, III, Ph.D.
Editor in Chief, Cancer Research
Professor, Gene Expression and Regulation Program
The Wistar Institute

Kevin Struhl, Ph.D.
David Wesley Gaiser Professor of Biological Chemistry and Molecular Pharmacology
Harvard Medical School

George Prendergast, Ph.D.
President, CEO and Professor
Lankenau Institute for Medical Research

Jennifer Ligibel, M.D.
Medical Oncologist
Dana-Farber Cancer Institute

FDA Questions Denosumab Safety in Advisory Meeting Documents
By John Gever, Senior Editor, MedPage Today
Published: August 11, 2009

FDA staff has expressed concerns that denosumab, the investigational biologic drug for osteoporosis, may increase risk of serious infections through its activity against an important immune system modulator.

The agency believes the drug -- provisionally trade-named Prolia -- could delay fracture healing as well. Some evidence suggests it could also promote tumor development and progression.

The concerns were revealed in briefing documents released in advance of a Thursday meeting of the agency's Advisory Committee for Reproductive Health Drugs, which will consider whether to recommend denosumab for approval.

Denosumab is a monoclonal antibody to RANKL, the receptor activator of nuclear factor-?B ligand. The molecule appears to help drive osteoclast development and activation, as well as playing a vital role in the body's defenses against infection.

If NF-?B is the immune system's "master switch," as it has been called -- controlling B- and T-cell differentiation and dendritic cell development -- then RANKL is the finger that flips the switch.

The drug's manufacturer, Amgen, filed last December for FDA approval of denosumab for preventing and treating osteoporosis in postmenopausal women, in women undergoing hormone ablation for breast cancer, and in men on androgen-deprivation therapy for prostate cancer.

Just this week, two of the registration trials for denosumab were published by the New England Journal of Medicine as early online releases. Those randomized, placebo-controlled studies showed that the drug was as effective as the best bisphosphonate drugs for osteoporosis.

The studies included more than 7,800 postmenopausal women with osteoporosis and close to 1,500 men with prostate cancer.

They also reported no indications of increased rates of serious infections, cancers, or most other serious adverse events, except for an increased incidence of eczema. (See Denosumab a Winner in Phase III Osteoporosis Trials)

The drug also boasts an extremely convenient dosing regimen -- subcutaneous injection every six months. Many clinicians believe this is a big advantage for denosumab, considering that compliance with daily oral medications for osteoporosis is notoriously poor.

But the drug's risk profile, especially with regard to infections and cancers in women being treated for postmenopausal osteoporosis, appears to be the FDA's chief concern going into the advisory committee meeting.

After pooling data from the clinical studies in postmenopausal osteoporosis submitted by Amgen (including phase I and II trials), agency staff found hints of potential problems.

"Overall, subjects in the denosumab group had a slightly increased incidence of serious infections," according to the briefing document. "There were more serious infections of the skin, ear, abdominal system and urinary tract. Also, endocarditis, infected arthritis and skin ulcers occurred more commonly in denosumab subjects. There were three denosumab subjects in phase I studies who developed pneumonia requiring hospitalization following a single dose of denosumab."

The document also noted that while Amgen did not perform carcinogenicity studies in animals because denosumab is not active in normal mice or rats, the clinical data showed a modest increase in certain malignancies in the human subjects.

"Three subjects receiving a high dose of denosumab in [a] dose-finding study died of a new malignancy," the staff review found. Those individuals received 100-mg doses, whereas 60 mg was used in the phase III studies and would likely be the recommended dose upon approval.

Pooled data from all the postmenopausal osteoporosis trials suggested "a slightly increased incidence" of breast, pancreatic, gastrointestinal, and reproductive-tract tumors.

Twice as many women discontinued denosumab versus placebo because of breast cancer, the reviewers noted -- 0.5% (20 cases) of patients receiving denosumab versus 0.3% (10 cases) of the placebo group.

Certain data also indicated that denosumab may produce unhealthy changes in bone structure, the review found.

According to the briefing document, both osteoclasts and osteoblasts were suppressed relative to patients taking placebo and alendronate. Markers of bone dynamics such as activation frequency, bone formation rates, and mineralizing surface were also much lower in denosumab-treated patients.

"This raises a concern that with long term use, suppression of bone remodeling may lead to complications such as delayed fracture healing, osteonecrosis of the jaw, or atypical fracture," the document said.

Neither of the two New England Journal of Medicine reports this week, however, gave any indication of clinical bone problems associated with denosumab. Authors of those studies said they found no signs of delayed bone healing after fracture and there were no cases of jaw osteonecrosis, a rare but frightening side effect of bisphosphonate drugs.

The FDA document confirmed that no actual cases of jaw osteonecrosis were seen in any of the osteoporosis or hormone ablation trials.

But one case was reported in another trial sponsored by Amgen in patients with multiple myeloma and metastatic cancer.

Also, the clinical data alleviated concerns about possible adverse cardiovascular events, such as promotion of atherosclerosis, that were hypothesized on the basis of its anti-RANKL mechanism.

And, deaths were no more frequent in denosumab groups versus placebo in the trials.

In light of the safety worries that still remain with the drug, the advisory committee will be asked to comment on whether a risk evaluation and mitigation strategy should be required as a condition of denosumab's approval.

The agency is not bound to follow its advisory committee's recommendations, but it usually does.

Extreme Diet and Breast Cancer Risk

UK researchers observing a small group of women who followed an extreme 900 calorie a day diet found they had reduced expression of a cancer growth gene and changes in blood biomarkers for breast cancer. If these findings are confirmed in larger trials, the researchers hope they will help experts recommend specific diet changes to women at higher risk of breast cancer so they can reduce their likelihood of developing the disease.

The study was conducted by Professor Anthony Howell, Director of the Breakthrough Breast Cancer Research Unit at The University of Manchester, and his team, and was published online on 1 August in the journal Cancer Prevention Research.

Previous studies have already shown that calorie restriction, more formally termed Dietary Energy Restriction (DER), reduces the risk of spontaneous breast cancer in rats and mice, and in women who follow DER before the menopause it seems to reduce the risk of getting breast cancer after the menopause.

However, what is missing from the science is reliable markers of DER so that robust DER regimens for preventing breast cancer can be designed. So Howell and colleagues set out to investigate some DER biomarkers in breast and fat tissue and blood (serum).

For the study they recruited 19 women aged between 35 and 45 who were either overweight or obese and assessed to be at moderate risk of developing breast cancer due to family history (their lifetime risk ranged from 1 in 6 to 1 in 3).

The women were randomly assigned either to follow a DER regimen (10 participants) or continue a normal eating pattern (9 participants) of about 2,000 calories a day for one menstrual cycle.

Before and after the trial, the women underwent biopsies of breast and belly fat tissue and also gave blood and urine samples.

To look at genetic changes, Howell and colleagues extracted RNA from whole tissues and breast epithelium. To look for biomarkers, the blood and urine sample were used to generate metabolic profiles.

The results showed that:
• Not surprisingly, DER was linked to significant reductions in weight.

• DER was also linked to changes in serum biomarkers of breast cancer risk, including insulin, leptin (a hormonal biomarker for body fat), total and low-density ("bad") lipoprotein cholesterol, and triglycerides (high levels of these are often linked to higher risk of a range of diseases).

• In both breast tissue, belly tissue, and some isolated breast epithelial cells, there was evidence that genes involved in key metabolic pathways for fats and other substances (glycolytic and lipid pathways) were less active ("significantly down-regulated").

• This included a reduction in the expression of Stearoyl-CoA desaturase (SCD), a gene linked to cancer growth. This is the first time this has been observed in breast tissue.
Howell and colleagues concluded that:

"Reduced expressions of genes in the lipid metabolism and glycolytic pathways are detectable in breast tissue following DER, and these may represent targets for DER mimetics as effective chemoprophylactic agents."

Howell told the media that he and his team wanted to thank the women who took part in the trial:

"The women who took part in this study made a major commitment to help us carry out this vital research."

"They enabled us to look for the first time at changes that occur within the breast tissue that may make cancer growth less likely. These results will now need to be tested in larger groups of women over longer periods of time," he added.

Dr Alexis Willett, Head of Policy at the UK charity Breakthrough Breast Cancer, said:

"We already know that the more weight a woman gains over the course of her adult life, the higher her risk of developing breast cancer will be after she has gone through the menopause. However, it is important to find out more about how lifestyle changes like losing weight can affect breast cancer risk."

"We wouldn't advise women to follow a diet of this kind as those who took part were closely monitored by a specialist dietician. We recommend that women maintain a healthy weight to reduce their breast cancer risk," added Willett.

Salinomycin Attacks Stem Cells in Breast Cancer

In tests in mice, salinomycin killed breast cancer stem cells far more effectively than some existing drugs, and slowed tumour growth.
The drug, a farm antibiotic, has yet to be tested in humans, the journal Cell reports.
But UK experts warned a human version could be some years away.
The reasons why, even following powerful chemotherapy, some cancers can grow back, are not fully understood.
Many scientists believe a key role lies with stem cells, which can be resistant to conventional chemotherapy, remaining to 'seed' new tumours and drive their growth.
The drug's potential was identified by researchers at the Massachusetts Institute of Technology, who tested 16,000 existing chemical compounds against breast cancer stem cells in the laboratory.
Those which performed the best were then tried in mice, and compared to existing drugs such as paclitaxel.
Salinomycin appeared to be 100 times better at killing the cells in a test tube, and treated cells were much less likely to start new tumours when injected into mice.
When given to mice with tumours, the growth of the cancer slowed.
However, the researchers stressed that it was too early to know if similar successes could be achieved in human cancer patients.
"Many therapies kill the bulk of a tumour only to see it regrow," said Professor Eric Lander, from MIT."This raises the prospect of new kinds of anti-cancer therapies."
'Very early research'
Dr John Stingl, group leader in mammary stem cell biology at Cancer Research UK's Cambridge Research Institute, said: "This is one of the biggest advances we have seen this year in this area of research. These scientists have demonstrated that it's possible to selectively target the rare cancer stem cells that drive tumour growth.
"This research also introduces a completely new way of identifying cancer drugs. The challenge for the future is to bring this class of drugs to the clinic and to identify the patients that are likely to respond to them."
Dr Alexis Willett, head of policy at Breakthrough Breast Cancer, added: "There is evidence that stem cells may enable breast cancers to form and grow.
"This research provides a clue as how to identify these cells and how they might be targeted and destroyed. "It's important to remember that this is very early research and it will be some time before it is clear whether this leads to an effective breast cancer treatment."
Story from BBC NEWS:

"Biomarkers of Dietary Energy Restriction in Women at Increased Risk of Breast Cancer."
Ong, Kai Ren, Sims, Andrew H., Harvie, Michelle, Chapman, Mary, Dunn, Warwick B., Broadhurst, David, Goodacre, Royston, Wilson, Mary, Thomas, Nicola, Clarke, Robert B., Howell, Anthony.
Cancer Prev Res 2009 2: 720-731.
Published online, August 1, 2009.
DOI: 10.1158/1940-6207.CAPR-09-0008

Sources: Manchester University.

Written by: Catharine Paddock, PhD
Copyright: Medical News Today

Ovary Removal Linked to Increased Lung Cancer Risk
New York Times
Women who undergo hysterectomies often have both ovaries removed along with the uterus in order to prevent ovarian cancer. But a new study suggests ovary removal may increase the risk of another seemingly unrelated ailment, lung cancer.
University of Montreal scientists stumbled onto the connection while investigating the relationship between lung cancer and hormones in women. They found no relationship between hormonal factors like menstruation patterns, child-bearing or breast-feeding histories and the risk of lung cancer. The researchers did, however, discover that women whose menopause had been induced medically were at 1.92 times greater risk of developing lung cancer than women who had experienced natural menopause.
“We were surprised — we had no prior expectation of this finding,” said Anita Koushik, a researcher at the University of Montreal’s Department of Social and Preventive Medicine and the first author of the study, published online in May in The International Journal of Cancer. “Aside from the fact that smoking increases your risk of lung cancer, the results of this study suggest that having a non-natural menopause contributes to an almost doubling of the risk.” She noted, though, that the findings could have occurred by chance.
The vast majority of women who had experienced a non-natural menopause had had both ovaries surgically removed, she added.
While smoking is the leading cause of lung cancer, other factors may play a role in enhancing the impact of the carcinogens in tobacco, Dr. Koushik said. In women, these factors could be hormonal. Both normal and cancerous lung tissue express estrogen receptors and may be influenced by levels of the hormone in the body, Dr. Koushik said. The patterns of expression are different in men and in women.
Medically induced menopause usually occurs at a younger age than natural menopause. Surgical menopause results in a sudden drop in estrogen levels, compared with the more gradual decline in hormone levels that occurs with natural menopause. Dr. Koushik suggested the increased lung cancer risk may be linked to the impact of plummeting hormone levels.
In the study, the scientists examined data on 422 women diagnosed with lung cancer in the greater Montreal area in 1996 and 1997 and compared them with 577 randomly selected control subjects. The women were asked about a variety of hormone-related factors, including when they got their first periods, how many children they had, whether they breast-fed their children and whether they had gone through menopause. The researchers also gathered detailed information about smoking, occupational history, education and family income.
The report is not the first to link ovary removal with an increased risk of lung cancer. A recent analysis of data from the Nurses’ Health Study, published in the journal Obstetrics and Gynecology in May, reported that women who had had hysterectomies but kept their ovaries lived longer than women who had had the procedure but whose ovaries were removed.
While those who had their ovaries removed were less likely to develop breast cancer and virtually eliminated their risk of ovarian cancer, they were more prone to heart disease and were at greater risk for other kinds of cancer, including a doubling of the risk for lung cancer among those women who never used hormone therapy.
(See 2009 SABCS Report on how Aromatase Inhibitors reduce lung cancer risk)

Blood Pressure Drug Blocks Newly Found Breast Cancer Gene

Blood Pressure Drug Losartan Shrinks Cancer Tumors by 30% in Study

By Gina Shaw
WebMD Health News
Reviewed by Louise Chang, MD

June 1, 2009 -- Researchers at the University of Michigan have identified a gene that may be involved in as many as one in five breast cancers. And the gene could be blocked by a common blood pressure drug.

The gene, AGTR1, caused normal breast cells to act like highly invasive cancer cells, both in the laboratory and in mice. When the mice were then treated with an FDA-approved blood pressure drug, losartan, tumors that overexpressed AGTR1 shrunk by 30% within eight weeks.
The Hunt for Breast Cancer Genes

The researchers identified AGTR1 by using gene expression profiling data to compare thousands of genes that might be linked to breast cancer. AGTR1 was overexpressed (or overly productive of its gene product) in 10% to 20% of all breast cancers -- second only to  HER2, which is found in 25% to 30% of all breast cancers and responds well to the drug Herceptin.

“HER2 ... makes breast cells cancer-like. That’s very similar to what we found with AGTR1,” says Daniel Rhodes, PhD, a research investigator in the Michigan Center for Translational Pathology and the lead author of the study, which appears in the June 1 edition of Proceedings of the National Academy of Sciences. Rhodes is also the founder and CEO of a cancer genomics company, Compendia Biosciences.

Breast cancer researchers have been looking for other targets similar to HER2 in order to develop more targeted treatments for women whose breast cancers are not HER2-positive and therefore do not respond to Herecptin.
Blood Pressure Drugs for Breast Cancer

Because AGTR1 is involved in the constriction of blood vessels, its activity is blocked by a class of drugs called angiotensin receptor blockers, which include losartan, the drug tested in this study. “This is particularly exciting, because losartan is such a safe and widely prescribed therapy,” Rhodes says. “This makes it much easier to do a clinical trial.”

If losartan really does block the cancer-promoting activity of AGTR1, why hasn’t anyone identified a lower rate of breast cancer among women taking the drug for high blood pressure?

“One would expect epidemiologic studies to show a reduction in BC [breast cancer] risk in people taking this drug,” says Clifford Hudis, MD, chief of the breast cancer medicine service at Memorial Sloan-Kettering Cancer Center in New York. “I don’t remember ever seeing hypertension and treatment for hypertension as indicators of lower breast cancer risk. We have lots of patients who get treated for breast cancer and take anti-hypertensives, so you would expect to see that pop out as an indicator of good outcomes.”

But not all high blood pressure drugs specifically block the AGTR1 receptor. “We think that true blockers to the AGTR1 protein would have the strongest effect, and these drugs, like losartan, are generally used as second-line therapies for hypertension,” Rhodes tells WebMD. "If only a few women in 100 are being treated with angiotensin receptor blockers, and only 10% to 20% of all breast cancers are AGTR1-positive, you’d need thousands of patients to see an effect.”
Developing a Test for AGTR1-Positive Tumors

But if there were a study in which losartan were given only to women with breast cancers linked to overexpression of AGTR1, it would be much easier to detect an effect. Before such a trial can be set up, however, scientists must first develop a way to easily detect AGTR1 overexpression.

Once that test is available -- something that should take only a few months, says Rhodes -- a clinical trial should be easier than usual to set up because of the availability of an existing, approved therapy whose side effects are known. “No trial is specifically planned yet, but we are talking with our clinical colleagues about it and there is a great deal of interest,” he says.

“If the data can be confirmed, it’s not a big stretch to imagine setting up a randomized study relatively easily,” Hudis says. “I definitely think this should be investigated further, although as always when we don’t yet have data in humans, you have to be careful and not jump to conclusions.”

The University of Michigan has filed a patent on AGTR1 and is seeking commercial partners.

New report states that breast ultra sounds are 100% accurate. Read on to see how misleading this is.

A new report has been released today to tell us all that breast ultrasounds pick up tumors 100% of the time in women under 40.


My tumor, which was found when I was in my 30s, was picked up on mammogram and when the docs did a follow-up ultrasound it was not there. The radiologist said that since it was not picked up on both, I should "watch and wait" for six months.... Fortunately I have a gyn who hates cancer as much as I do and he insisted on an immediate biopsy. That resulted in finding a grade 3, highly aggressive Triple Negative Breast Cancer next to my chest wall.  If I had followed the three most dangerous words in the English language, "watch and wait" my TN tumor would have made a nice, comfy home for itself in the chest wall and the vascular and lymphatic system. Would I still be here? I don't know- Ferne isn't... and she was told to wait.

Here is the article- tell your friends to not take this as gospel because it could be deadly. The TRUTH IS: Women under 40 need better screening. It is NOT just replacing mammography with ultrasounds. If they really gave a damn about us they would find a way to get EVERYONE Breast MRIs which can find tumors as small as 7mms. But who is going to pay for that? We have research into erectile dysfunction to fund.... the Space Shuttle to launch to change the spark plugs on the International Space Station.... Think about it.

CHICAGO (Reuters) - Breast ultrasounds found 100 percent of suspicious cancers in women under 40 who found lumps or other suspicious areas of the breast, offering a cheaper, less-invasive alternative to surgery or biopsies, U.S. researchers said on Wednesday.

They said targeted ultrasound -- which examines just the area of the breast where a lump is identified -- should become the standard of care for women under 40.

The findings may address some of the concerns raised by a federal advisory panel about breast exams done by women or doctors to investigate lumps or hot spots in the breast, which most often turn out to be harmless.

In a controversial set of recommendations issued last month, the U.S. Preventive Services Task Force recommended that women not be taught to perform self breast exams because they often result in worry and expense for tests, biopsies and unnecessary surgery.

"That concerns us because while breast cancer in young women is rare, it absolutely does occur. Often, those cancers are only diagnosed because the woman noticed the lump in her breast or her doctor noticed a lump in her breast," said Dr. Constance Lehman of the University of Washington and director of imaging at the Seattle Cancer Care Alliance, who presented her findings at the Radiological Society of America meeting in Chicago.

"There are harms that follow after a woman does a self breast exam -- unnecessary surgeries, unnecessary biopsies. To that point, what we're saying is if you use imaging appropriately you can avoid those harms," Lehman said in a telephone interview.

Lehman did two studies testing the effectiveness of ultrasound to distinguish between potentially cancerous lumps and harmless masses in younger women.

In one, they studied more than 1,100 ultrasound exams of women under age 30. In the second, they studied 1,500 exams in women aged 30 to 39.

In both studies, ultrasound correctly identified the cancers and all of the benign breast changes. The only cancer not found was in a region of the breast that was not identified as an area of concern. Instead, it was identified by a full breast mammogram.

"Less than 3 percent of the patients that presented in this way had cancer. But it's important for us to find those patients that did have cancer," Lehman said.

"We had 26 women whose cancers were diagnosed because they brought the lump to the attention of their doctor, or their doctor brought the lump to the attention of the breast imaging specialist," she said.

Lehman said in the United States there is no standard way of treating women under age 40 who find a lump in their breast.

"Some of them go to the operating room to have the lump removed. Others have it followed. Others have a needle biopsy and we wanted to bring some clarity to this treatment," she said.

She said ultrasound is a quick and easy test that uses sound waves to create an image of the breast. It typically costs $100 to $200 per exam.

Lehman said using ultrasound could help balance some of the harms of overtreatment with the benefits of self breast exams in women under age 40, who are too young for routine mammogram screening even under the American Cancer Society guidelines.

The task force also recommended against routine mammogram screening for women in their 40s for many of the same reasons, a change the American Cancer Society and many other breast cancer experts reject.

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