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Direct Link To This Post Topic: San Antonio Breast Cancer Symposium Updates
    Posted: Dec 12 2014 at 5:09pm
San Antonio Breast Cancer Symposium 2014
A Report to the Triple Negative Breast Cancer Community
Post 1 | December 10, 2014

“The work done in the last three or four years has put breast cancer at the forefront of immunotherapy.” - Nora Disis, MD, University of Washington

Greetings from San Antonio.

There’s a buzz this year.

Oncologists don’t get excited too easily. They are a cautious group, driven by data, veterans of a world in which many studies fail, progress is often measured in inches and new discoveries reveal deeper complexities. This year, it’s different. There’s a growing belief that we are on the verge of new era in cancer treatment that has the potential to change the way we think about cancer and the way people experience these diseases.

The reason for this excitement is the emergence of immunotherapy to treat a wide range of cancers--including breast cancer. Immunotherapy harnesses the body’s natural defenses to recognize and fight cancers. The principle sounds simple enough, but the reality of immunotherapy is amazingly complex, requiring an ever deeper understanding of the ways in which cancers interact with the immune system.

For people facing triple negative breast cancer, immunotherapy could open the doors to new therapies and new hope both for curing early TNBC and for greatly improving the outcomes for advanced disease. While it is important to realize that all of this work is in its early stages, the rapidity with which new knowledge is being translated into new treatments means that patients will have access to these new approaches beginning now and the options will increase within the next few years. It is also important to know there are currently no immunotherapy drugs approved to treat breast cancer. All breast cancer related immunotherapy research is being done in cancer centers through clinical trials.

TNBC: “The Hallmark of Immunogenic Cancers”

Researchers have known for decades that some cancers are immunogenic--meaning that the immune system appears to recognize these cells as abnormal or foreign, and at least, in some cases, react to them. Melanoma and kidney cancers topped that list. As immunotherapy has progressed, other cancers, including lung, bladder and hematologic cancers have also been shown to respond to these approaches. Breast cancer was not thought to be a good candidate for immunotherapy. New work, however, demonstrates a strong connection between the immune system and some breast cancers. Triple negative is in the words of Dr. Disis, “the hallmark of immunogenic breast cancers.”

Tumor Infiltrating Lymphocytes

One study presented today looked at the correlation between tumor infiltrating lymphocytes (TILs) in the stroma or tissue environment around the tumor and responses to chemotherapy. TILs are indicators that the immune system is responding to the tumor. Previous studies have reported that patients with stromal TILs have a better prognosis and respond better to chemotherapy than those who do not. The trial, led by Edith Perez, MD, of the Mayo Clinic, Jacksonville, Florida found that patients with large numbers of lymphocytes (lymphocyte predominant breast cancer or LPBC) have increased recurrence free survival compared to those with non-LPBC tumors. Approximately, 60% of TNBC is lymphocyte predominant.

Why is this important? First, it provides an important marker for identifying which TNBC patients are most likely to respond well to adjuvant and neoadjuvant therapies and to treatment for advanced disease. Second, it creates the possibility of developing new treatments aimed at getting more lymphocytes into tumors in order to enhance the immune response. Third, there are certain genetic mutations that are associated with immune suppression--the BRAF mutation, for example, found in about 50% of melanoma patients. BRAF inhibitors are known to increase two key indicators of immune response---knowledge that could be applicable to TNBC in the future.

In the next few days, we will report on other key findings from this remarkable symposium, including a Phase I study on an immunotherapy agent in triple negative breast cancer patients.

Living Beyond Breast Cancer Survey Reports High Levels of Anxiety for People with All Stages of TNBC

The first survey of psychosocial needs for women with triple negative breast cancer reports that women with this disease have higher levels of fear, anxiety and worry at all stages than women with other breast cancer subtypes. The study also showed that TNBC patients have a significantly stronger preference for information tailored to their cancer subtype. Living Beyond Breast Cancer (LBCC) partnered with the Triple Negative Breast Cancer Foundation to identify patients and conduct the survey.

“Women with triple negative breast cancer are information seekers.” Jean Sachs, MSS, MLSP CEO of LBCC said. “And they are frustrated when they don’t have more treatment options.”

One striking finding was the extent to which TNBC patients continue to feel fear and anxiety at all points of their diagnosis and treatment. “While women with all breast cancer subtypes report a reduction in negative emotion over time from treatment to post treatment, this change is less profound in TNBC women and appears to be driven nearly entirely by concern about the disease,” the study found.

The study was conducted between November 2013 and January 2014 and compared responses of 656 women diagnosed with TNBC with those of 1954 women with other subtypes of breast cancer. The results of the survey are being presented at two SABCS poster sessions. LBCC will release a public summary of the finding in January 2015.

- Christine Wilson
  Trustee, TNBC Foundation

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Direct Link To This Post Posted: Dec 12 2014 at 5:10pm
San Antonio Breast Cancer Symposium 2014
A Report to the Triple Negative Breast Cancer Community
Post 2 | December 11, 2014

A Promising Study--An Important Step Forward

"Let's not wait. Let's move these trials forward so we can benefit our triple negative breast cancer patients."
- Nora Disis, MD

A Phase I study of a new immunotherapy agent has produced promising results in a subset of patients with advanced triple negative breast cancer. The drug, prembrolizumab (Keytruda), is one of a group of very promising agents that block the PD-1 protein on the surface of cancer cells. The study, presented on December 10, at the San Antonio Breast Cancer Symposium is an example of the rapid progress being made in the area of immunotherapy, but also comes with some with precautions about what this study means and where it will lead.

Prembrolizumab got a lot of attention at the 2014 meeting or the American Society of Clinical Oncology when the results of a trial using this new monoclonal antibody to treat advanced melanoma were announced. Prembrolizumab, also known as MK-3475, produced such positive responses in this population that the drug was given accelerated approval by the Food and Drug Administration and approved for this use in October. Studies for other tumor types including lung, bladder and head and neck cancers have had response rates of between 20-34%. These results were important because they occurred in patients with advanced disease and many of the responses were long lasting.

The KEYNOTE-012 study results were reported by Rita Nanda, MD, of the University of Chicago. This was a very small, Phase I trial in which 32 women with advanced triple negative breast cancer were given prembrolizumab as a single agent. All of these patients had received multiple chemotherapy regimens prior to entering the study. The overall response rate was 18.5% or five patients. One woman had a complete response, four had partial responses. An additional seven had stable disease. What is significant is that the five responders remain in remission more than 11 months after starting treatment--an extraordinary durable response for this group of patients. Two are still on treatment and two discontinued the therapy after 40 weeks.

The side effects seen in this trial were generally mild and tolerated well. They included rashes, fatigue and joint pain. One patient had hypothyroidism. Overall 56% of the treated patients had some reported side effects, mostly grade I and 2.

Prembrolizumab works as what is known as a checkpoint blocker. Cancer cells can block T cells from attacking them by expressing PD-1 and its ligands PD-L1 and PD-L2 on their surface. Prembrolizumab and other checkpoint blockers inhibit that expression and allow T cells to recognize and destroy the cancer cells. The study included only patients whose tumors were identified as expressing PD-1--approximately 60% of triple negative patients.

An interesting side note to this report was the difference in how two audiences reacted to the study results. I heard these data presented twice, first to a group of medical and scientific reporters at the press conference, and then to the packed auditorium of cancer specialists attending the symposium. The reporters were skeptical, asking "given the relatively low response rate, is this really a positive study?" The medical people were excited and encouraged by the study results, seeing this as a potentially important step forward in developing new treatments for TNBC and a solid basis for continuing studies.

"These results are right in the ballpark with what we are seeing with other tumor types, said Dr. Disis who led the discussion of the session. "We have the biology, the response rates and the toxicity we are seeing across the board. It's time to move onward. We are looking for a better therapy that will cause long lasting protective immunity."

Both the presenters and the discussant stressed the importance of conducting additional trials with larger groups of patients, identifying the factors in addition to being PD-1 positive that predict response and combining pembrolizumanb with other agents to increase the overall response rate. A larger, multicenter Phase II trial is planned for early 2015.

- Christine Wilson
  Trustee, TNBC Foundation



Edited by ArleneB - Dec 12 2014 at 5:12pm
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Direct Link To This Post Posted: Dec 12 2014 at 5:13pm
San Antonio Breast Cancer Symposium 2014
A Report to the Triple Negative Breast Cancer Community
Post 3 | December 12, 2014

Take Aways...

Here are some “take-aways” from this year’s San Antonio Breast Cancer Conference. Let’s start with two issues that have been the center of discussion and study over the last few years.

Is pathological complete response (pCR) an acceptable endpoint for evaluating the success of a clinical trial? The standard clinical trial is structured to measure one or more of these criteria:

     Overall response rate (ORR)--the percentage of participants in the study who get a complete or partial response to the therapy being tested

     Disease free survival (DFS)--the length of time that a person remains without detectable disease from the time of treatment

     Progression free survival (PFS)--the length of time from treatment until the cancer begins to grow again. This is sometime called relapse free survival (RFS).

The advent of neo-adjuvant therapy has led to a new criterion--whether the treatment causes all visible signs of the cancer to disappear before the primary treatment, usually surgery. In medical terms this is called a pCR. Initially, there were questions as to whether a pCR correlates with improved survival or better outcomes, but that debate has ended. The evidence is now solid that patients who achieve a pCR have lower rates of recurrence and longer survival than those who do not. This has been clearly demonstrated in people with TNBC.

The advantages of neoadjuvant therapy are clear for the TNBC population. Women who are treated successfully with their initial therapy do well, those who recur face a difficult and often limited clinical course. The goal of treatment is to prevent recurrence in as many people as possible. Neoadjuvant therapy improves those odds. Using pCR as an outcomes measures also allows for faster assessment of whether drugs are effective and more flexible clinical trials.

At SABCS 14, a neoadjuvant trial comparing single agent paclitaxel (Taxane) and nab-paclitaxel (Abraxane) in 400 women with high risk, early breast cancer showed a clear advantage for the Abraxane arm.  Thirty-eight percent of the women in the Abraxane arm achieved a pCR vs. 29% of the Taxane arm. Both groups received standard chemotherapy as part of the regimen.

considered standard of care for TNBC patients with BRCA1 mutations.

Should platinum based chemotherapy be standard therapy for some subsets of TNBC patients? The data are now convincing on this issue as well. Platinum based chemotherapy is now considered standard of care for TNBC patients with germline BRCA1 and 2 mutations. This is true for both early stage and metastatic disease.

New Trial to Test Immunotherapy/Chemo Combination
On another front, a Phase I trial on which Celgene and Bristol Myers Squibb are collaborating opened today (12/12). The study will take place at 15 centers across the United States and involve three cohorts of patients, one with pancreatic cancer, one with non small cell lung cancer, and one with TNBC and HER2- breast cancers. These patients will receive three cycles of nab-paclitaxel (Abraxane) and be randomized to receive or not receive nivolumab (Opdivo),  a PD-1 checkpoint inhibitor that has shown activity in a number of cancer types. The patients in the trial will all have recurrent or metastatic disease and have failed one previous treatment. This is a Phase I trial designed to establish safety and preliminary effectiveness, but it is also one of the first trials to combine chemotherapy with immunotherapy for breast cancer patients.

Weight Management Makes a Difference for TNBC Patients
The WINS trial may sound like ancient history. It was opened in 1994 to study if reducing dietary fat for women with early stage breast cancer improves survival. The trial enrolled patients who consumed at least 20% of their calories in fat and randomized them into those who got an intervention--reduced fat--and those who did not. The follow was shaky but, in the final analysis, presented at SABCS 14, there was no significant difference in overall survival between the two groups--except in the subgroup of women with hormone receptor negative disease. Researchers believe that the real benefit came from weight loss and increased physical activity as opposed to fat reduction. The NCI is reviewing for a large scale study on lifestyle factors and cancer survival and two trials are currently underway in Europe looking at dietary factors and physical activity.

As the meeting wraps up, what are the important messages for the TNBC community?

     Immunotherapy is rapidly emerging as a very promising area of treatment for triple negative breast cancer.

     This work is still in its early phases. A great deal more research needs to be done to determine how best to use these new agents, which patients will benefit, how to combine them with other therapies and in what circumstances and sequences to use them.

     Although the goal of defining a targeted therapy for TNBC that is the equivalent of Herceptin remains elusive, treatment for this disease is becomingly increasingly individualized. A key to this is identifying the subtypes of TNBC and understanding the clinical significance of these biological differences in making treatment decisions.

     Neoadjuvant therapy is improving the odds for newly diagnosed TNBC patients, lowering the risk of recurrence.

The next report will include comments from two experts on the importance of this meeting and an expanded interview with the investigator who conducted the LBCC survey of people with TNBC.

- Christine Wilson
  Trustee, TNBC Foundation



Edited by ArleneB - Dec 12 2014 at 5:14pm
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Direct Link To This Post Posted: Dec 16 2014 at 10:27am
San Antonio Breast Cancer Symposium 2014
A Report to the Triple Negative Breast Cancer Community
Post 4 | December 16, 2014

Wrap Up: The Doctor’s Perspective

Linda Vadhat, MD, is a breast cancer specialist and researcher from Weill Cornell Medical Center in New York City. She provided insight into the 2014 San Antonio Breast Cancer Symposium.

In her view, this year’s meeting had a number of very positive take-aways for the triple negative breast cancer community, but no one major practice changing development.

“I have to say there is a real emphasis right now on triple negative breast cancer and on understanding the biology--the genomics, the immunology, the stem cells. These are all very important steps forward, although they are just beginning to have an impact on the clinical outcomes for triple negative patients.”

Dr. Vadhat said that she thought the Phase I trial of pembrolizumab (Keytruda) was an excellent example of an important first step. She noted that the five responders (out of 27 in the trial) were not the patients who had high levels of PD-1 expression. “We are very encouraged by the activity of this group of drugs, but we really aren’t sure right now whether PD-1 is a biomarker. We need to know more about how these drugs work and in which patients they work.”

She also pointed to the trial that compared paclitaxel (Taxane) with nab-placlitaxel (Abraxane) as useful but not landscape changing. “The dose of Abraxane was a little higher than that of paclitaxel, so we have to wonder a little about that. Abraxane is also a very expensive drug and cost is becoming more of a factor for some patients in making decisions. It’s important to have these data and this option for our patients in the neoadjuvant setting where we can really make a difference.”

Vadhat believes that understanding the subtypes of triple negative breast cancer will become increasingly significant in developing effective treatment. “We need to know what’s driving these cancers to treat them effectively, and it is now clear that there are distinct biological characteristics that influence how these cancers grow and spread--and that we will be able to target in the future.”

In her own research, Vadhat focuses on inhibiting copper dependent processes as a way of preventing invasion and metastases in triple negative breast cancer patients. Copper is essential to the ability of cancer cells to form blood vessels, especially in the microenvironment around the tumor. Vadhat has concluded a Phase I study and is planning a larger Phase II study in this promising area.

She also believes that in the near future, we will move from talking about cancers in terms of the organ or site in which they develop to describing them by their genomic characteristics.


A Conversation with Kathy Swiger about the LBBC Survey of Triple Negative Breast Cancer Patients

Kathy Swiger stands by her poster in the “Psychosocial and Behavioral” Section of the vast hall at the San Antonio Breast Cancer Symposium. the second of two that Living Beyond Breast Cancer (LBBC) has presented at this important meeting. There’s a lot interest from the attendees, both advocates and clinicians. They study the data and ask Swiger questions about the results.

“The posters are just the tip of the iceberg,” she says pointing the densely worded panels behind her. “There is so much more data in the full survey.”

Swiger is the lead investigator on the study and clearly has a deep passion for her work. She notes that before the actual survey, the LBBC team conducted a series of focus groups across the country to identify issues important to the TNBC community.

“In some areas, we had women who drove four hours to participate in a focus group. It was that important to them to have their voices heard and to have the chance to talk to people who were sharing their experience. In San Francisco, the group asked if we would pay for another two hours of parking so they could go to lunch together after the session--and keep talking to each other. We found that many of these women feel very isolated. Their experience is different from that of other people with breast cancer.”

For some women, this isolation is geographic--being in an area in which there are few others with a tnbc diagnosis. That could be either rural or urban. For others, it stems from an age discrepancy--or huge differences in the treatment course. One young African American woman from a small town in North Carolina talked about going to a support group in which all the other participant were older women dealing with the effects of hormone therapy.

Swiger also noted that many of the focus group participants struggle with the term “triple negative.” “We found that many people have never heard of triple negative breast cancer, or know little about it before their diagnosis. They hear the term triple negative and to some it sounds like ‘three strikes and you’re out.” It’s very frightening. Then they look online and what they find can be scary and confusing.”

The focus groups were to used to develop the survey which compared the responses of 656 triple negative patients with those of 1954 women with other breast cancer subtypes. The survey revealed significant differences in the kinds of information the tnbc patients want and the levels of anxiety, fear and worry they experience from diagnosis to treatment. The full survey results will be made public in early 2015.

“There is such a strong need among the triple negative patients both for information that is specific to their disease and what they are experiencing,” says Swiger, “and for person to person peer interaction, the opportunity to share those experiences. This survey is just a first step in addressing the information and emotional support needs of this group of people.”

The Triple Negative Breast Cancer Foundation worked with LBCC to identify potential responders for the survey. TNBCF also sponsored the first triple negative specific track at LBCC’s annual conference held in September in Philadelphia. That support included scholarships to bring people with TNBC to the conference from all over the country. TNBCF has committed to repeating that sponsorship in 2015.

- Christine Wilson
  Trustee, TNBC Foundation




Edited by ArleneB - Dec 16 2014 at 10:29am
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