Triple Negative Breast Cancer - Breaking News!

We endeavor to keep up with all the advances in the treatment of Triple Negative Breast Cancer. The following is a collection of the very latest advances from the wonderful reporters who are following the work of researchers around the world.

We thank Onclive.com author Laura Panjwani;
The Federation of American Societies for Experimental Biology;
Cynvenio Biosystems, Inc. and Businesswire.

Many updates can also be found on our blog- http://nosurrenderbreastcancer.blogspot.com/

Beta blockers may improve effectiveness of triple negative breast cancer treatments
Published on March 2, 2016

Source:
Federation of American Societies for Experimental Biology

New research published in the March 2016 issue of The FASEB Journal, shows that a commonly prescribed class of high blood pressure drugs may have the potential to slow the growth of triple negative breast cancer tumors. These drugs, called "beta blockers" work by counteracting the pro-growth effect caused by adrenaline by affecting the the beta2-adrenoceptor.

"Previous studies have linked increased stress with accelerated onset of metastasis in some forms of breast cancer," said Michelle L. Halls, Ph.D., a researcher involved in the work from the Drug Discovery Biology Theme at Monash Institute of Pharmaceutical Sciences at Monash University in Parkville, Victoria, Australia. "By understanding how stress accelerates invasion in aggressive breast tumor cells, this work will inform future studies into whether beta-blockers could be a useful adjuvant therapy in the treatment of some aggressive breast cancers."

To make their discovery, Halls and colleagues examined how an aggressive triple negative breast cancer cell responds to the stress hormone adrenaline. They found that an aggressive breast cancer tumor cell has a cell surface protein called "beta2-adrenoceptor" that can binds both beta-blockers and the stress hormone adrenaline. When bound to adrenaline, the beta2-adrenoceptor on these tumor cells stimulates a positive signaling loop to accelerate invasion. When bound to beta-blocker, however, the accelerated invasion of these cells was decreased.

"This is excellent research that shows us that we still do not know the full potential of many of the drugs sitting in most medicine cabinets," said Thoru Pederson, Ph.D., Editor-in-Chief of The FASEB Journal. "Not only does this shed light on how to potentially improve the effectiveness of triple negative cancer treatments, but it also sheds light on the full effect that these common drugs have on our bodies."




Growing Role of Checkpoint Inhibitors in Breast Cancer
Author: Laura Panjwani

This article appeared here: http://www.onclive.com/web-exclusives/mittendorf-explains-growing-role-of-checkpoint-inhibitors-in-breast-cancer

Please Visit Onclive.Com for the latest news on breast cancer.

There is still a lot to be learned regarding the use of checkpoint inhibitors in breast cancer, but the field is advancing rapidly. Several agents have shown potential in recent trials.

In the phase Ib JAVELIN study, treatment with the PD-L1 inhibitor avelumab demonstrated promising results for patients with metastatic breast cancer. After a median follow-up of 10 months, the overall response rate (ORR) in all patients with PD-L1-expressing metastatic breast cancer was 33.3%. The highest response rate of 44.4% was seen in patients with PD-L1- positive triple-negative breast cancer (TNBC), although other subtypes also saw benefit.

The trial includes patients with tumors that are HER2- negative/HR- positive (42.9%), triple-negative (34.5%), and HER2-positive (15.5%). Around 7% of breast cancer cases in the trial were not identified as a particular subtype. In the full population of the study, the ORR included 1 complete response and 7 partial responses. An additional 23.2% of patients experienced stable disease with avelumab, for a disease control rate of 28%. Of those who responded, 5 had TNBC (8.6%) and 4 were PD-L1-positive. Responses were also observed in patients with HER2-negative/HR-positive breast cancer (2.8%) and in those with HER2-positive disease (3.8%).1 In addition, in the ongoing phase Ib KEYNOTE-028 basket trial—which is evaluating pembrolizumab (Keytruda) in patients with PD-L1-positive advanced solid tumors of all types—an ORR of 12% was seen in patients with ER+/HER2- advanced breast cancer.

In previously reported data from the phase Ib KEYNOTE-012 trial, pembrolizumab demonstrated an ORR of 18.5% in patients with PD-L1–positive TNBC. Elizabeth Mittendorf, MD, PhD is an associate professor in the Department of Surgical Oncology at the University of Texas MD Anderson Cancer Center.

In the following interview with OncLive, Mittendorf talked about checkpoint inhibition studies in TNBC, potential ways to make other subtypes more immunogenic to improve response, the role of PD-1, and what’s next in the field of immunotherapy in breast cancer.

OncLive: How has the use of checkpoint inhibition in breast cancer evolved in the past year? Mittendorf: We have additional data now for multiple agents in TNBC; this time last year we just had pembrolizumab.

There is a cooperative group study trial proposed to evaluate the role of checkpoint blockade in TNBC patients who receive neoadjuvant chemotherapy and have persistent disease. Our group at MD Anderson is just starting a trial looking at checkpoint blockade in combination with chemotherapy in the neoadjuvant setting for what we are defining as high-risk TNBC.

Very importantly, at SABCS (San Antonio Breast Cancer Symposium) in December 2015 there were data presented on the use of checkpoint inhibitors in subtypes of breast cancer other than TNBC. The JAVELIN trial included ER-positive, HER2-positive, and TNBC breast cancers. There are also several ongoing studies and concepts in development that are moving checkpoint inhibitors, which are showing themselves to be safe, into the neoadjuvant setting as well as the adjuvant setting.

Much of the checkpoint inhibitor research in breast cancer has been focused on TNBC. Do you see potential for other subtypes as well? TNBC is an area with no targeted agents, so much of the focus has been based on need. However, if you think about checkpoint blockade, it is a drug that works by taking the breaks off of T cells, so in order for it to have an effect there needs to be T cells present. If you look at the published data, it has shown that the presence of tumor-infiltrating lymphocytes (TILs) is greatest in the TNBC subtype when compared to the other subtypes. Based on that, the thought is that TNBC will be more susceptible to checkpoint blockade. However, there is an opportunity to turn these other breast cancer subtypes, like HR-positive breast cancer, more immunogenic and then come in with checkpoint blockade after that.

How could that potentially be achieved?
There are studies that have looked at strategies like cryoablation and radiation. There are data that suggest that chemotherapy in some cases can be immune stimulating. Vaccines are also a possibility. There are strategies investigating these novel intratumoral injection agents like talimogene laherparepvec (T-VEC). There are also strategies using other drugs that modify the innate immune system. There are a lot of possibilities.

What role does PD L1 status play in the use of checkpoint inhibitors in breast cancer?
When this class of drugs initially started showing benefit in breast cancer, people suggested that the expression of PD-L1 was required—that it was a biomarker needed to predict response to treatment. I think most of the experts now feel that is not the case. The reason for that is that it is very dynamic how PD-1 expression can go up and down in a tumor depending on aspects of the microenvironment. The JAVELIN trial did have some interesting data that suggested that the expression of PD-L1 by the tumor was not predictive of response, but the expression of PD-L1 by other immune cells in the microenvironment did appear, at least in TNBC, to potentially be predictive. They refer to these as ‘immune hotspots.’ I do not think the trials should be designed to require PD-L1 positivity in order for patients to enroll, but that needs to be further evaluated in biospecimens collected from patients who are on the studies.

What’s on the horizon for immunotherapy in breast cancer?
I think we are going to move to an era where it is not limited to anti-CTLA-4 or anti-PD-1/anti- PD-L1 agents. There will be an opportunity to move agents that are currently being evaluated in other tumors to be evaluated in broad, phase I basket trials where many tumor types are included and to look at different agonist antibodies against co-stimulatory molecules. An example of that is OX40 or 4-1BB. I think we will also look at antagonist antibodies against inhibitory molecules other than just CTLA-4 or PD-1.

In breast cancer, the really interesting work is going to be focused on better characterizing the immune aspects of the tumor microenvironment with our current standard of care therapies, so that we can rationally add them in.

There will likely be a role for immunotherapies in most if not all of our breast cancer patients. But we need to—as a group—approach this in a very thoughtful manner. We have therapies that work in breast cancer; we cure a lot of patients. We need to figure out what those therapies are doing to the immune response so that we can better design trials that will incorporate these immune agents to be a benefit to our patients. We have a different challenge than colleagues in fields like melanoma had, where they really had few effective systemic therapies.

References
1. Dirix LY, Takacs I, Nikolinakos P, et al. Avelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: A phase Ib JAVELIN solid tumor trial. Presented at: San Antonio Breast Cancer Symposium; December 8-12, 2015; San Antonio, TX. Abstract: S1-07.
2. Rugo HS, Delord J-P, Im S-A, et al. Preliminary efficacy and safety of pembrolizumab (MK-3475) in patients with PD-L1–positive, estrogen receptor– positive (ER+)/HER2-negative advanced breast cancer enrolled in KEYNOTE-028. Presented at the 2015 San Antonio Breast

Cancer Symposium; San Antonio, TX; December 8-12, 2015. Abstract S5-07





Non-invasive ‘Liquid Biopsy’ Technology May Provide Early Warning System for Metastasis and Lead to Improved Targeted Outcomes

March 03, 2016
LOS ANGELES--(BUSINESS WIRE)--

Cynvenio Biosystems, Inc., a diagnostics company dedicated to enabling the new era of individualized medicine for all cancer patients, today will honor Triple Negative Breast Cancer Day by launching a clinical trial for women with triple negative breast cancer (TNBC) using the company’s non-invasive liquid biopsy technology to monitor participants and identify early signs of metastasis. An event for breast cancer advocates, including women with the disease and those enrolling in the trial, will take place this morning in Beverly Hills at the Pink Lotus Breast Center - the first site to participate in the nationwide study.

“The ‘watch and wait’ plan is not reassuring to our patients; therefore, our goal is to provide women a better method for monitoring their health, and hopefully, cancer-free existence.”


Of the estimated one million cases of breast cancer diagnosed annually worldwide, some 170,000 or more will have the TNBC subtype, which means these women test negative for estrogen receptor, progesterone receptor, and Her-2 receptor gene expression. Despite a relatively favorable response rate to chemotherapy, TNBC-classified patients are more likely to develop distant recurrence and die from breast cancer within five years of diagnosis compared with other patients, and one-third of all TNBC patients will eventually develop metastatic disease. Younger women, African Americans, and Latinas are at highest risk.


“Currently there is no effective way to monitor women who have completed standard therapy for TNBC and who remain at high risk of recurrence and metastases.” said Paul Y. Song, MD, Chief Medical Officer of Cynvenio. “Our LiquidBiopsy®-based solution, which uses a simple blood draw and includes monitoring a woman’s immune system for signs of cancer recurrence, may help find cancerous cells well before they embed themselves into organs or bone. These cells can then be analyzed to identify specific targeted therapies in hopes of improving outcomes.”


“We strive to provide the highest quality breast care medically and technologically possible, so we are excited to be the first center in the country to participate in this cutting-edge research,” said Kristi Funk, MD, Founder of the Pink Lotus Breast Center. “The ‘watch and wait’ plan is not reassuring to our patients; therefore, our goal is to provide women a better method for monitoring their health, and hopefully, cancer-free existence.”
André de Fusco, Cynvenio’s Chief Executive Officer added: “This trial is an important milestone for our company and for the field of breast cancer research. It represents the culmination of four years of intense bioengineering development and we are thrilled to support Drs. Funk and Song in their quest to change the patient monitoring paradigm. Most importantly we hope our work will lead to tangible improvements in the standard of care for triple negative breast cancer survivors. ”


About the Trial
The new study will use Cynvenio’s ClearID™ genomic test, powered by its LiquidBiopsy® technology, in combination with the NK Vue™ blood test from ATGen Global, which is distributed by Cynvenio in the U.S. The NK Vue test monitors the immune system – specifically the presence of natural killer (NK) cells – and can be used as a tool for assessing changes in patients with conditions where innate NK cell activity has been shown to be reduced, such as in some types of cancer. There has been a strong correlation between low NK cell activity and increased presence of circulating tumor cells. In this study, patients who show low NK levels will receive further analysis with the ClearID test to molecularly characterize circulating tumor cell and cell-free DNA present in their blood for genetic alterations that may support specific treatment regimens. More information about the trial is available at https://clinicaltrials.gov/show/NCT02639832.


About Cynvenio Biosystems, Inc.
Cynvenio is a commercial stage clinical diagnostics company that leverages its proprietary LiquidBiopsy® multi-template technology for the molecular characterization of tumor cells from a standard blood draw. Commercial labs and research institutions are powered by Cynvenio’s LiquidBiopsy platform, which includes automated instrumentation, consumables/reagents, patient sample kits, and bioinformatics for sequencing rare cell populations. Oncology practices and individual physicians can also access the LiquidBiopsy system with zero upfront investment by ordering the ClearID™ blood test from Cynvenio’s CLIA/CAP lab or its clinical partners. ClearID and LiquidBiopsy are cornerstones in the emerging field of genomic peripheral blood monitoring. They are used to rapidly assess patients’ evolving mutations in support of precision medicine strategies. ClearID is reimbursable in the United States. Cynvenio is headquartered in Westlake Village, California (Los Angeles). For more information, please visit http://www.cynvenio.com and www.liquidbiopsy.com.
LiquidBiopsy® is a registered trademark and ClearID™ is a trademark of Cynvenio Biosystems, Inc.
NK Vue™ is a registered trademark of ATGen Ltd. (Seoul, Korea)

Contacts
Bioscribe, Inc. Nicole Litchfield, 1-415-793-6468 Nicole@bioscribe.com


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