American Association for Cancer Research 2017

I begin with a personal comment. I know that as a non-profit organization, TNBCF does not take “political” stands. Neither does the American Association for Cancer Research. That doesn’t mean that organizations dedicated to improving the treatment and care of people facing cancer can look away and avoid speaking up for what matters most. This year, the AACR meeting, an extraordinary tribute to the power of science and medicine takes place under some very dark clouds.

Five minutes before I attended a session on “The ACA and its Potential Impact on Cancer Patients,” I read an article in the New York Times that stated a new proposal from the Freedom Caucus “effectively casts the Affordable Care Act’s preexisting conditions provision aside.” The article’s author, Margaret Sanger-Katz, specifically to what this would mean to cancer patients.

The reality of this scenario became very clear during the ensuing discussion. Chiaro D’Agostino is an intelligent, articulate woman, a former Italian teacher with a MA in Italian culture. She is single and self-employed. Two years ago, at age 43, she was diagnosed with stage III TNBC. In October, her disease recurred and she is now on a clinical immunotherapy trial for her metastatic cancer. Her ACA policy has paid for all of her expenses, including her clinical trial. She has access to the top care that is keeping her alive, and she is terrified what it will mean to lose that coverage. Her daily anxiety adds heavily to the burden of her cancer experience. She is one voice, among so many.

At the same time that Congress and the Administration are considering stripping the ACA of essential benefits and rolling back the protection for people with pre-existing condition, the proposed budget cuts funding for the NIH by almost 20%. In this environment, I am surrounded by people from all over the world who are presenting new discoveries and who believe that we have truly entered a remarkable era of progress in understanding and treating cancer and other diseases. It is impossible to comprehend a plan that cuts this country’s commitment to medicine and science, to patients and caregivers that drastically. The effect will be enormous and immediate, and have a direct impact on the cancer community.

Finally, one of the things that makes science so beautiful is that it truly is global. Scientists and physicians come to this meeting, and others, from all over the world. Major studies are done in cancer centers in multiple countries. People share data and ideas in ways that transcend boundaries. We need to make sure that we don’t build walls of any kind that exclude the people who make this possible.

As members of the triple negative breast cancer community, this is a time speak up, to take action, to make sure your voices are heard by the people who are making these decisions. Your stories are powerful. You can make a difference, both individually and speaking together in a unified voice. Contact Congress, as often and in as many ways as you can. Deliver these messages:

● There are 18 million people living with cancer today–and that doesn’t count our caregivers, families and friends.

● It is critical that people facing serious illnesses have insurance that provides guaranteed access to healthcare, including clinical trials. Be careful on this one as some people use word “access” to mean the ability to choose plans, not access to actual care.

● Science matters. Today, we are seeing a revolution in understanding cancer and other serious disease. There is also important work in improving quality of life. That progress is fueled by research which requires funding. Do not cripple this country’s research effort by slashing funding for the NIH and other scientific agencies and programs.

● Respect and protect the contributions of scientists and physicians from all over the world and assure that people from every country can continue to come here to learn, train, share their expertise and care for patients.

In the first presentation I attended, the researcher, David Hyman,was discussing a very elegant study that involves looking at the drug neratinib in treating different subtypes of HER2 mutant cancers. This trial, SUMMIT, is a big Phase 2 “basket” trial which means that it accepts patients with many different types of cancers, as long as they have an identifiable HER2 mutation. He noted that while the study was closed for a number of tumor types, the TNBC arm was still open.

That stopped me for a moment, well more than a moment. How was it possible that TNBC patients could have HER2 mutations. The answer was provided by TNBCF grantee Eddie Yang, “The most common type, he said, “the one that is not found in TNBC is the result of having too many copies of the HER2 gene, causing over expression of that protein. There are actually many variants of the HER2 mutation. These are found in the DNA of breast cancer cells but not normal cells. They are not inherited and do not result in over amplification of the gene. These somatic HER2 mutations occur much less frequently than gene overexpression, but may be targetable. With TKI inhibitors and possibly other agents as well.”

This is another strong argument for making sure that every breast cancer patient undergoes genetic profiling–from a lab that has the experience and expertise to look for both the common and these less common mutations. Dr. Yang also pointed out that HER2 status can change with time and treatment. Some women who are initially positive become HER2 negative, and vice versa, sometimes years after diagnosis. It is essential to rebiopsy tumors at critical decision making points.

Dr. Hyman’s study also illustrated just how precise precision medicine is becoming. The HER2 mutations occur in relatively small percentages of people with a number of cancers, one to seven percent, depending on the tumor type–and there are a lot variations. The effectiveness of neratinib was influenced both by the tumor type and the HER2 mutation involved. More studies are planned, including with TNBC to learn more about how best to target and treat these mutations.

Lou Weiner, MD, director of the Lombardi Comprehensive Cancer Center at Georgetown, has been around for a long time, and he has been interested in immunotherapy for his entire career as a cancer researcher. He shakes his head in amazement as he describes the excitement about this rapidly emerging cancer therapy. “It wasn’t that long ago, really just a few years, that immunotherapy was considered kind of a ‘stupid pet trick’ in cancer treatment, interesting but not very useful. We know now that is not the case. We now have abundant evidence that immunotherapy is a central component of treating cancers, and we are challenging a lot of our dogmas about how it works.”

While many types of breast cancer still appear to have relatively low levels of immunogenicity–meaning their growth is not heavily influenced by the immune system–TNBC is the exception. TNBC tumors often have high levels of mutations and show evidence of inflammation in the tissue surrounding them. In addition, high levels of immune cells called TILS are often found in the tumor. All of these make TNBC a promising candidate for immunotherapy and the number of trials are increasingly rapidly.

One trial, reported at AACR involves the drug atezolizumab, an engineered monoclonal antibody that inhibits PD-L1. In this Phase 1 study, women with mTNBC had improved overall response rates and longer survival than expected. The response rate was better, 26% in those who the atezolizumab as first line therapy than for those who had already had two or three previous regimens. For those women who did respond, the duration of response was encouraging, 21 months.

The study provides more support for the role of immunotherapy in treating TNBC. “This is small but significant,” said Peter Schmid,MD, who presented the data. “The fact that we have a group of metastatic TNBC patients with good responses and longer survival time gives me hope. We need to learn how to use this treatment to benefit more patients. This is a real indication that earlier treatment and potentially combination therapies will increase the response rate for these patients.”

Eddie Yang, PhD of the University of Alabama at Birmingham, is the recipient of a TNBC grant through the AACR. I spoke with him at the meeting and he told me that his study has completed accrual and that he expects to present preliminary data at the San Antonio Breast Cancer Symposium. Yang is interested in studying DNA repair pathways and developing novel treatment approaches to target triple negative breast cancer.

“We are looking at what makes these tumors vulnerable and how we can combine therapies to exploit those weaknesses,” he said. “It involves hitting the cancer at more than one point in the pathway, kind of upstream and downstream”

The TNBCF funded study is a small Phase I trial with 20 patients. Yang was not able to discuss the data at this point but did say that the results were promising and that he was excited about continuing the research.

Photo by © AACR/Todd Buchanan 2016 Contact Info: todd@medmeetingimages.com

Computational molecular biology. What is it and why does it matter to the TNBC community? Briefly stated and way under simplified, computational molecular biology is an emerging tool that is opening new doors to understanding the biology and behavior of cells. It is also Christina Curtis’s special area of expertise. Dr. Curtis, an assistant professor in the school of medicine at Stanford University, is the 2016 recipient of a grant funded by the Triple Negative Breast Cancer Foundation and its partner Carol’s Crusade for the Cure. Her work focuses on developing ways of predicting which cancers are more likely to recur, both in individual patients and in groups of patients with triple negative breast cancer.

“We are interested in using innovative computational and analytic approaches to improve the diagnosis and treatment for cancers,” Dr. Curtis says. “Why do some people develop metastatic breast cancer?

Knowing which cancers are likely to recur is critical for many reasons. If you know which tumors are going to behave aggressively, you can treat them more aggressively, early in the process. You can also spare patients with less high risk cancers from treatments that will not help them. Traditionally, decisions about the degree of risk for any patient have been based on the clinical characteristics of the tumor. How big is it? Are there lymph nodes involved? What do the cells look like under the microscope? Those factors are still important but today, the biology and the genetics of any individual cancer are playing an increasingly role in making personalized decisions about treatment.

Dr. Curtis’s work begins with doing a genomic analysis of actual tissue acquired in biopsies. She then uses that information to develop a three-dimensional model of the tumor that will behave like the actual cancer cells. She can look at the full range of mutations and see which ones are most likely to produce metastases or resist treatments.

“Our original model was for colon cancer,” she says. “We are now applying what we learned to triple negative breast cancer. TNBC is a complex group of tumors with very diverse genomic and molecular profiles. It is also a cancer for which there is truly an urgent need to understand the biology and use that knowledge to improve the outcomes for patients.”

One challenge Dr. Curtis faces is getting the tissue for analysis. “We need tissue from both primary and metastatic tumors so we can see how these cells evolve and change, understand what mutations occur during that process. It can be difficult to get the metastatic tissue because many patients don’t want to undergo biopsies that don’t have any therapeutic benefit, or the metastatic tumors are in hard to biopsy places.”

Dr. Curtis promises to keep the TNBC community up to date on the progress of her work. She and her colleagues are at the forefront of a rapidly emerging approach to science that brings together clinicians and experts fields ranging from physics to engineering to high end computing. The result is a an array of new tools and new insights that are transforming the way we understand and treat cancers.

The big breast cancer story coming out or AACR this year was the MINDACT study. This was a huge, international and impressive clinical trial that analyzed the utility of genomic risk assessment in deciding whether a patient should have adjuvant therapy.

This is not a study that has enormous implications for the TNBC community because many women diagnosed with this type of breast cancer are classified as being at high risk for recurrence. Those women need and benefit from adjuvant or neoadjuvant chemotherapy. Only 9 percent of the people in this study had TNBC.

The study involved 6693 patients with early breast cancer. These patients are often faced with a decision as to whether to have adjuvant chemotherapy after their surgery. While it is clear that adjuvant therapy reduces the risk of recurrence in many patients, it is far less clear which individuals actually benefit. That means a percentage of breast cancer patients experience the health and emotional issues that come with that treatment unnecessarily. This study was designed to provide better information on how to assess the risk of recurrence and make decisions about chemotherapy for individual patients.

The study used both clinical and genomic data to make the risk assessment. The genomic data came from the Mammaprint assay which tests for 17 genes. Mammaprint is widely used in Europe but the same information can be obtained from the Oncotype DX assay and several other similar tests. Patients were classified as having:

Clinically low/genomically low risk–This group did not get chemotherapy
Clinicall high/genomically high risk–This group did get chemotherapy

Clinically low/genomically high risk–These are the groups with the highest level of uncertainty
Clinically high/genomically low risk

The latter two groups were randomized into either chemo or no chemo. The results were clear. There was no statistical benefit for undergoing adjuvant chemotherapy. These patients, all with early breast cancer, had basically identical disease free survival rates–in the 95 percent range.

Dr. Martine Piccart of the Universite LIbre de Bruxelles, who presented the results, noted that the study makes it clear that physicians and patients need both clinical and genomic data to assess risks and make decisions about chemotherapy after surgery. “The MINDACT trial has had a major educational impact in Europe,” she said. “It has really demonstrated that genomics can provide important information treating patients with early breast cancer.”