One of the most promising new trends in cancer science is the search for personalized medicines – finding treatments that are right for individual patients and identifying those that might not work based on a patient’s genetic makeup and medical history.
In 2009, Komen provided $6 million in research funding to an Indiana University team looking for genetic markers that could predict which patients would respond to a new experimental drug. Soon, the research from this Komen Promise Grant opened promising new doors about genetics and treatment side effects. The team was led by Indiana University’s Bryan Schneider, M.D. (one of our Komen Scholars) and the late David Flockhart, M.D., Ph.D., along with patient advocate Mary Lou Smith, Esq., co-founder of Research Advocacy Network.
We spoke to Dr. Schneider about this grant to learn more.
Komen: Dr. Schneider, thanks so much for your time and for the important work you do in the fight against breast cancer. Could you walk us through the ins and outs of your Komen Promise Grant?
Schneider:Of course. The main goal was to deliver better personalized medicine. We did this by leveraging two large randomized trials (involving about 5,000 patients from around the globe), comparing an experimental drug (bevacizumab, or Avastin) to standard treatment with chemotherapy. Our goal was to use genetic data that we collected from patients to identify those individuals who would benefit from treatment.
Along the way, we realized that we also ended up with a great deal of detailed information about the side effects patients suffered from – regardless of which drug they were given.
Komen: How can this study change medicine now?
Schneider: I think we, as researchers, do a great job of determining which drugs will work for which patients, but often overlook serious treatment effects, such as peripheral neuropathy or congestive heart failure.
I can tell you from my own experience that some patients fear the word “chemo” more than the word “cancer.” If we can understand who is at increased risk for these life-altering side effects, it could impact how patients receive therapy, or if maybe an alternative therapy or foregoing therapy altogether is a better option. For now, the most important takeaway is that we will be able to tailor our therapies not just to those we think will benefit, but also to avoid therapies in patients we think may suffer.
Komen: What did you learn about specific side effects?
Schneider: Well, we learned a great deal about this one common side effect called peripheral neuropathy, or inflammation of the nerves. It results in a number of symptoms like numbness or tingling, and it can make seemingly simple tasks (like brushing your teeth) really challenging. And even worse – it can be irreversible. Our study revealed one biomarker in particular in patients who were more likely to develop this side effect, which could be extremely important information when patients are making treatment decisions.
We also found that African-Americans are much more likely to experience neuropathy. We actually found a gene specific to this population that could indicate which individuals are at increased risk – again, vital information for treatment decisions.
Another serious side effect we discovered a great deal about was congestive heart failure. It’s more rare, but absolutely terrible if it does happen. We were able to identify a biomarker that indicates increased risk of this side effect as well.
Komen: You clearly had patients’ needs at the center of your work. Can you tell us about the role patient advocates played in this study?
Schneider: Having patient advocates on the grant is an amazing asset. They not only help develop the project aims, but keep us grounded about what matters to patients. For example, our initial goal was to identify who might benefit from bevacizumab. Unfortunately, we found that this particular drug probably won’t be important for breast cancer. But, our patient advocates pointed out that we could still use the amazing genetic and treatment data we had gathered to ask other important and meaningful questions, such as who might suffer the most from treatment side effects, and get valuable information for patients.
Komen: What do you want people to walk away knowing about Komen and this Promise Grant?
Schneider: None of this work would have happened without Komen’s funding. Komen is one of the few organizations that recognize that it’s not all about discoveries at the molecular level. The more important question is: how will we take these findings and make it relevant to patients? Komen has been amazing at supporting work like this Promise Grant which is directly focused on making an impact in patients’ lives.
As far as what’s next – honestly, we have a long way to go. I wish we could say we’ve cured cancer and minimized all side effects, but we still have more work to do in terms of understanding how these biomarkers affect treatment regimens, and how we can take this to the patient and into clinics. Until we get there, we’ll continue to need support from organizations like Komen and individuals everywhere who help make this work possible.
The thought that it might be breast cancer never crossed Kathy’s mind when she felt an excruciating pain in her chest last November. After working as a nurse and then hospital president with the Franciscan Health System in the Seattle area for 26 years, Kathy Bressler had just accepted an exciting promotion with the same company, and was planning a move to Omaha, Nebraska.
She thought the sudden and burning pain she felt may have been a ruptured muscle – after all, her pain ultimately went away, and it’s a common thought that “if it hurts, it’s probably not breast cancer.” But after encouragement from her husband, she went to get a mammogram. It came back clean, and Kathy was ready to move on with the next chapter of her life. But the results of a breast ultrasound, which revealed a 1.7 cm tumor near the surface of her skin, set her life on a new path.
Kathy is no stranger to breast cancer, losing both her mom and grandmother to this terrible disease. She had been actively involved with Komen Puget Sound: racing, walking, serving on their Board of Directors and as Board President– doing anything she could to help end this disease.
Now faced with her own diagnosis, Kathy knew she wanted to put breast cancer as far behind her as possible, opting for a bilateral mastectomy (despite being a candidate for less extensive surgery). The surgery revealed three more tumors that had gone undetected, and the pathology report came back: triple negative.
Even though TNBC only accounts for approximately 15 percent of all breast cancers, Kathy was still surprised to learn that her recommended course of treatment would include the same chemotherapy her mother received… 25 years ago.
Triple negative breast cancer (TNBC) is difficult to treat because of what it lacks: estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor 2 (HER2). These three types of receptors drive the majority of breast cancers, and as a result, established therapies that target these receptors are ineffective against TNBC, making it especially difficult to treat.
While great progress has been made in treating many forms of breast cancer, current treatments for TNBC often target all of the actively dividing cells in the body (including the healthy ones!) resulting in inadequate tumor responses and often severe side effects.
This aggressive subtype of breast cancer also disproportionately affects women with a BRCA gene mutation, young women and African-American women. There is great urgency in the breast cancer community to better understand and treat this aggressive type of breast cancer – to offer women like Kathy and so many others better treatment options.
Susan G. Komen has invested more than $98 million in research and clinical trials focused on TNBC, including over 60 active research grants covering everything from the basic biology of a TNBC breast cancer cell to promising treatments that are currently in clinical trials. Here are five projects that we are particularly excited about:
- Komen Scholar Dr. Jennifer Pietenpol of Vanderbilt University has discovered 6 different subtypes of triple negative breast cancer, each with unique genetic differences. These differences could be used to develop targeted therapies for TNBC, which are lacking as treatment options. Dr. Pietenpol is currently developing clinical trials to test these targeted therapies.
- Dr. Giorgio Seano, a young investigator at Massachusetts General Hospital, is working to improve the effectiveness of traditional radio- and chemotherapy in TNBC by testing a newly identified drug that may reduce the overgrown network of blood vessels known to strengthen and support these breast tumors.
- Another Komen-funded young investigator, Dr. Kareem Mohni of Vanderbilt, is using big data approaches to identify genetic characteristics of TNBC tumors that may be most responsive to a promising new drug combination.
- Also at Vanderbilt, Dr. Justin Balko is tackling the question of how to best prevent recurrences of TNBC following neoadjuvant chemotherapy followed by surgery. Dr. Balko is studying TNBC cells that survived chemotherapy to identify potential drug targets that could be exploited to take down these highly resistant cells.
- Finally, Dr. Max Wicha of the University of Michigan received a Komen Promise grant to study the role of breast cancer stem cells in TNBC, and whether the increased presence of these cells in women of African descent may contribute to the increased likelihood of developing TNBC in these women. Dr. Wicha is also testing several potential drugs that target breast cancer stem cells in early stage clinical trials.
This groundbreaking research will bring new options and hope for the thousands of women and men facing TNBC around the globe. But until we get there, we think Kathy said it best:
“TNBC is rare, so I understand why we don’t yet have all the answers. But it’s out there, it’s still happening and it’s really aggressive. It’s not the end of anything – it’s the beginning of a new journey. Yes it will change you forever, but it doesn’t have to be for the worse.
“And to those who ask why I lost my hair, I say, because we don’t know enough yet, so pull out your pocketbook! Until it’s no longer 1 in 8, we must continue this fight, we must continue to raise awareness and dollars, and we must continue to walk until we’ve ended breast cancer once and for all. ”
Komen has worked with public health and political leaders for more than 30 years to push for broad, systemic and lasting changes in the fight against breast cancer. We engage policymakers at every level of government to make sure breast cancer is a priority, giving a voice to more than 3 million breast cancer survivors in the U.S. and those who love them, in Washington, D.C. and every capital across the country.
We were delighted when President Obama announced a new Cancer Moonshot initiative led by Vice President Joe Biden – an initiative that aims to accomplish a decade’s worth of advances in the fight against cancer in five years. Our President and CEO Dr. Judy Salerno declared Susan G. Komen “ready, willing and able,” eager to lend the resources and expertise we’ve gathered in our more than 30 years to push progress across the cancer spectrum and realize our vision of a world without breast cancer.
Releasing his Fiscal Year 2017 budget earlier this week, the President included a $1 billion (3.2 percent) increase for the National Institutes of Health (NIH), including a $680 million (13 percent) increase for the National Cancer Institute (NCI), to fund the Moonshot.
But as is so often the case, funding new programs means “compromises” have to be made – and unfortunately it came in the form of a 20 percent reduction in funding for the National Breast and Cervical Cancer Early Detection Program (NBCCEDP).
While health care reform has increased access to breast and cervical cancer screening services for many women, the program was only reaching one in 10 eligible women at last year’s funding levels.
As a country, we cannot afford to lose funding for this program which provides vital, high-quality breast and cervical cancer screening services to low-income women in every community – women who would otherwise be unable to afford it. Even before budget details were released, ensuring funding for the NBCCEDP was among Komen’s top advocacy priorities.
Our 2016 advocacy priorities, identified as the policy issues that have the greatest potential impact on Komen’s mission, include:
- Support expanded federal funding for all biomedical research, especially breast cancer research at the National Institutes of Health (NIH) and Department of Defense (DOD);
- Support state and federal funding for the NBCCEDP;
- Advocate for policies to improve insurance coverage of breast cancer treatments and screening, (specifically, increased access to drug therapies and limiting out-of-pocket costs for diagnostic mammography); and
- Evaluate state and federal policies to increase awareness, education and access to clinical trials for all patient populations.
As the 114th Congress and state legislatures reconvene, Komen will work to ensure that these issues – and the millions of individuals they affect – are top-of-mind for policymakers everywhere. Because as the President’s budget revealed, our work is as relevant and important as ever.
We look forward to working with staff, volunteers, grantees, researchers and friends in communities across the U.S. to ensure that breast cancer issues are front and center – and to a successful 2016!
By Groesbeck Parham, MD
Komen-funded researcher working in Lusaka, Zambia
Over the past 30 years I’ve had the privilege of working as a gynecologic cancer surgeon in sub-Saharan Africa in the field of women’s cancer prevention and treatment.
For the last 10 of those years I’ve lived full-time in Zambia, where I’ve worked side by side with some remarkable African clinicians as we sought to build a national cervical cancer prevention program in a country where healthcare resources are unimaginably low, compared to those with which I was accustomed in the U.S.
There were days when it seemed desperate. Then there were times when our supplies and funds were relatively abundant and we dreamed big dreams.
We would feel the Spirit of Lack creeping in, as we thought: “You don’t have enough to get the job done, so why even try”; “It’s too difficult to do under these circumstances thus you will fail”; “Nobody else really cares”; “What makes you think you can innovate and try something that’s never been tried before, and be successful at it?”
The Spirit of Abundance, on the other hand, encouraged us: “If you put your nose to the grindstone and do the best you can, it will eventually happen.”
Our determination pushed us. We were not interested in giving up, and so, we chose to focus on the abundance.
We were able to build an innovative program that has screened over 250,000 Zambian women for cervical cancer for the first time in their lives, and prevented countless numbers of unnecessary deaths.
Prior to our work, only 10,000 women had ever been screened for cervical cancer in Zambia between 1964 and 2005. The Zambian government is now leading efforts to expand this program across the nation.
As we now take on the task of breast cancer control we again hear similar sounds coming across our eardrums:
“Breast cancer is a very complex disease and can’t be managed in a country with low resources”;
“The cost of treating breast cancer is too expensive for poor economies to afford”;
And just as before, we refused to listen to the negativity. We made the decision to disrupt the many barriers to breast cancer early detection and treatment in Zambia, and as usual the resources began to flow, this time in the form of a series of Susan G. Komen-funded initiatives.
The first was support for the formation of an umbrella organization (Cancer Prevention Alliance of Zambia – CAPRAZ) to bring together all pre-existing breast and cervical cancer advocacy groups in Zambia, to amplify and expand breast cancer awareness opportunities and prevent redundancy.
Second, Komen funding made it possible for cervical cancer screening nurses to be trained to perform clinical breast examinations on women attending their clinics.
Komen funds also helped to train radiographers and general surgeons to perform breast ultrasound and ultrasound-guided core biopsy of palpable breast masses, while also improving the breast cancer care skills of these healthcare providers.
Critical to the success of these efforts have been Zambian trainees with an eagerness to learn, as well as a superb breast cancer surgeon, Dr. Ronda Henry-Tillman from the University of Arkansas, who had an uncanny ability to effectively and compassionately communicate and educate both in the clinic and the operating room.
Today CAPRAZ is active, and breast cancer care is expanding and improving. Cervical cancer prevention nurses are performing clinical breast examinations on all women within the target age range. Women found to have palpable breast masses or other complaints (bloody nipple discharge, breast pain, etc.) are referred to two newly formed breast specialty clinics that provide diagnostic ultrasound and ultrasound-guided core needle biopsy of breast masses. Two general surgeons are incrementally learning how to provide modern, high quality, breast cancer surgical care.
In fact, since the Komen-funded training programs ended in January 2015, over 3,000 women have undergone clinical breast examinations by nurses, 122 referred for breast ultrasound and 62 biopsied. Of the women that were biopsied, 11 breast cancers were identified.
One of the most remarkable successes is the sizes of the breast masses found in women diagnosed with cancer – generally between 2 and 5 cm. In comparison, women who visit the national cancer center have tumors that are very large – between 10-15 cm.
We are the fortunate recipients of another Komen grant that will allow us to build on our past accomplishments. We plan to test whether combining all the services we now offer into a single visit, will impact the survival of those with cancer by decreasing delays in diagnosis and treatment.
We look forward to the challenges and the positive messages from the Spirit of Abundance. After all, it appears that it’s the key to making something out of nothing.
Q&A with Martine J. Piccart, M.D., Ph.D., Winner of the 2015 Brinker Award for Scientific Distinction in Clinical Research
In the quest for personalized medicine, scientists have been studying why some breast cancers respond to certain therapies and others don’t. Dr. Martine Piccart, the recipient of this year’s prestigious Brinker Award for Scientific Distinction in Clinical Research, has been coordinating international clinical trials and other collaborations, thriving for real impact on better treatments and outcomes for breast cancer patients. But it hasn’t always been easy. We recently had a chance to chat with Dr. Piccart and learn more about what motivates her in her work.
1. How could your research help individuals facing breast cancer today and in years to come?
In the past, the clinical trial work done through Breast International Group (BIG), a group of international scientists who participate in global collaborations to make significant advances in breast cancer research and contribute to the faster development of better treatments, focused primarily on conducting trials in early breast cancer in the adjuvant setting. Several of those trials are now considered to be landmark, contributing to significant breakthroughs, and paving the way toward more personalized treatment of the disease.
Indeed, BIG trials are helping many patients today: HERA has already contributed to a major breakthrough in treating HER2-positive breast cancer; BIG 1-98 put aromatase inhibitors on the map; and SOFT changed how we treat young women with breast cancer. Another trial that can potentially improve the quality of life of many patients is MINDACT, the results of which will help determine which specific women within a population of breast cancer patients may not need chemotherapy.
Finally, a few years ago, BIG decided to expand its efforts to cover research in advanced (metastatic) breast cancer. We launched AURORA in 2014, an ambitious molecular screening research program aimed at understanding the drivers of breast cancer metastasis, and defining which tumors respond to treatment. Metastatic and primary breast cancer tissue specimens will be collected and analyzed for the first time on an international scale. By uncovering the molecular mechanisms underlying metastasis, we expect to be able to develop more personalized treatments for our patients in the future.
2. What made you decide to focus your research on clinical trials testing new therapeutic agents and incorporating translational research?
Women whose cancer is not responding to current therapies badly need innovative compounds with new mechanisms of action and smart combinations. New drug development remains challenging but is incredibly exciting today, given our much-improved understanding of the molecular basis of the disease. Translational research is vital for the future, because it provides the link between the discoveries in the laboratory (basic science research) and their application for the benefit of patients (clinical research). It has already succeeded in expanding our medical knowledge and bringing many discoveries to the clinic. Translational Research is our biggest hope for decreasing over- and undertreatment of our patients due to the current “one size fits all” approach.
3. What was the biggest challenge that you had to overcome in your career?
It hasn’t always been easy to keep a healthy balance between family and work. With a husband and three daughters, we have often had to come up with creative solutions. I have a fantastic husband who’s supported me throughout my entire career and who’s given me the room, opportunity and motivation to pursue a career in oncology. However, what I found more challenging was establishing myself in a predominantly male professional environment. You have to prove yourself every step along the way. When I was appointed president of ESMO (European Society for Medical Oncology), I was the first women to hold this position. And this was only a few years ago. Women still have a long way to go, but perceptions are slowly changing, and I’m positive that my daughters won’t encounter as many obstacles along the way.
4. What, in your opinion, is the most recent progress in breast cancer research that patients should be aware of?
Personalized medicine has made significant progress with key discoveries in the field of breast cancer treatment – namely with the development of endocrine therapies and anti-HER2 therapies. With the great work of basic and translational scientists, we have a better understanding today of the molecular mechanisms that drive resistance to these very effective “targeted” therapies, and we are witnessing the development of new agents able to delay endocrine resistance and resistance to the anti-HER2 agent trastuzumab. These agents allow better control of advanced disease and are now being tested in early breast cancer as well, where they are expected to successfully treat the disease.
5. What would you predict will be the next big breakthrough for breast cancer patients?
I believe that the practice of oncology is entering a ‘revolution’ rather than undergoing an ‘evolution.’ Although we’ve been talking about personalized breast cancer treatment for several years, we’re just now on the verge of taking a giant leap from dream to reality. Increasingly sophisticated technologies will continue to help us to further dissect breast cancer into the individual molecular aberrations driving the disease. We see a growing number of biomarkers being identified and tested for their potential with targeted therapies. Along with these new molecularly directed therapies, we are likely to witness the birth of a new treatment modality – namely immunotherapy – which may play an important role for certain breast cancer subtypes. Essential for the success of these new approaches are innovative clinical trials. Driving this highly innovative research forward is a high priority for BIG, its group members, and its partners around the world – whom I sincerely thank for their great support over the years.
6. What does receiving the Brinker Award for Scientific Distinction in Clinical Research mean to you?
I am of course extremely honored to be granted such a prestigious award. Today, as BIG co-founder and chair, much of my energy is devoted to building a strong international network of academic groups and their centres that is committed to ‘driving’ the breast cancer clinical and translational research agenda. This international nonprofit organization was founded just over 15 years ago, and today unites 56 academic research groups from around the world, leading more than 40 trials to date. Our approach through BIG comes at a crunch time for clinical research, and it will allow for better screening of more patients, and the selection of specific subpopulations of patients, in which we will be able to test and tailor new drugs. I hope to use this model to change our approach to clinical trials in cancer, with the benefit of patients in mind.