BCRF sat down with Dr. Daniel F. Hayes to discuss his current work and interest in breast cancer research. Read on to learn more.
Q: Tell us about yourself as a scientist and how you became interested in breast cancer research. Did you ever seriously consider another kind of career than that of the sciences?
A: I am a practicing medical oncologist who does translational research. As a result, I conduct research in both the clinical and laboratory settings. My principal research interest is the generation and validation of tumor biomarkers for breast cancer patients.
I decided to go to medical school after considering a career teaching high school and coaching sports. I had no interest in oncology early in medical school, but as a junior medical student, I was assigned to the oncology ward at Indiana University - an idea I was originally against. By chance, my attending physician was Dr. Lawrence Einhorn, who is known for his work using cisplatin (platinum-based chemotherapy) to cure testicular cancer. Dr. Einhorn's research greatly increased the survival rate of all testicular cancer patients, even those whose cancer had spread or metastasized. Dr. Einhorn, a very charismatic man, inspired me to become an oncologist, and also encouraged me to go outside of Indiana. I went to University of Texas/Southwestern in Dallas for my residency, and then was selected for my fellowship at Harvard's Dana-Farber Cancer Institute, with the idea of working on testicular cancer.
At Dana-Farber, Dr. Emil Frei, then physician-in-chief, assigned me to the lab of Dr. Donald Kufe, who is known for his work in breast cancer. As our work progressed, I got one foot in the breast cancer clinical program with Dr. Craig Henderson and kept my work going with Dr. Kufe. It was a great opportunity, and I eventually published the first reports concerning the development of the CA15-3 blood test, which is currently used world-wide to monitor the progression of patients with breast cancer and their response to treatment.
All the years I've been in oncology, I have been surrounded by fantastic colleagues, many of whom coincidentally are also BCRF grantees. After I spent 15 years at the Dana-Farber, Dr. Marc Lippman recruited me to join him at Georgetown's Lombardi Cancer Center, and then I moved with him to University of Michigan, where we have a fabulous group of clinicians, clinical researchers, and laboratory investigators interested in breast cancer. It is really a great place to accomplish what we are trying to do: change practice in this disease.
Q: Briefly describe your BCRF-funded research project. What are some laboratory and/or clinical experiences that inspired your work? What are your primary goals for this research?
A: BCRF funds two projects that I'm involved in: one is on pharmacogenomics, the study of genes for the metabolism of drugs, with my fellow grantee, Dr. James Rae at the University of Michigan, and the other is related to my role as Chair of the Correlative Sciences Committee of the North American Breast Cancer Group (NABCG, formerly known as The Breast Cancer Intergroup). I will focus on my work through the NABCG first.
NABCG is a network of US-based breast cancer clinical trial cooperative groups sponsored by the National Cancer Institute (NCI). BCRF support has been critical in NABCG's activities, particularly those of the Correlative Science Committee (CSC). The CSC was established as a rigorous peer-review committee, which assesses and determines which projects could gain access to the precious biological samples collected from patients who participated in NCI breast cancer trials since the 1990s.
As CSC Chair for several years, I - along with my colleagues - noticed that sometimes projects would be approved but then the researchers couldn't perform the research because of the lack of funding. The costs of some of these projects were very modest, and although the science is superb, they were almost not worth the enormous effort to write a formal NCI grant. With BCRF support, we have been able to provide funding to individual investigators so that they can analyze tissues and new markers for clinical response rapidly and rigorously. Most of these projects aim to help identify people who would or would not benefit from a specific treatment.
In addition, BCRF support has allowed us to convene several workshops on such topics as pharmacogenomics, high throughput sequencing, and the Ki67 marker. The workshop on the Ki67 marker gave us an opportunity to "harmonize" researchers on how to use and assess this marker, which measures how quickly cells are "turning over."
We also collaborate on correlative science activities with Breast International Group (BIG), with whom we are currently building an informational website to link the organizations. This website (which went live in January 2011) will link with the one we already have for correlative sciences in the North American Group, and give lab scientists, from either NABCG or BIG, the ability to learn about the work that has already been done in his/her area of interest. More importantly, researchers can determine what specimens we have available for future studies and how to access them through our peer-review systems.
Q: What direction(s)/trends do you see emerging in breast cancer research in the next 10 years?
A: I've been a medical oncologist for 26 years, and the advances over the last two and a half decades have been extremely important. Yet, they seem to have come about unbelievably quickly. Investigators such as Drs. Chuck Perou, Matthew Ellis, and Gordon Mills have led us to the realization that "breast cancer" is comprised of many different kinds of disease. This "fragmentation" gives us a better idea of what the different types of breast cancer are and what contributes to their growth. This information has already provided clinically useful tools and in the future will even better help lead to our goal of "personalization" or individualization of therapy.
In addition, collaboration will become more important than ever to progress. Now that we have a clearer picture of the complexity of breast cancer, we also know that all breast cancers cannot be treated, or cured, the same way. Also, the current financial climate has created additional challenges for the research community. Working together and sharing resources is ever more critical to our success.
Q: What other projects are you currently working on?
A: The other BCRF-funded project that I am working on, with Dr. James Rae, examines a woman's genetic makeup in relation to her response to endocrine therapy. Approximately 70% of all breast cancer cases are hormone receptor-positive, the growth of which is mostly fueled by estrogen. About 60% of these patients will respond to some form of endocrine therapy, which seeks to reduce or inhibit the production of estrogen and is divided into anti-estrogens (e.g. tamoxifen or raloxifene) or aromatase inhibitors (AIs). Although there are clear differences among the medications with respect to overall response and side effects, it is not currently possible to identify which patients will benefit the most from either form of therapy.
Therefore, Dr. Rae and I are studying how inherited gene variants affect patients' response. We started (with our colleagues in the Consortium on Breast Cancer Pharmacogenomics) by focusing on CYP2D6 in the metabolism of tamoxifen. Although this has not panned out the way we had hoped, we are now moving on to study other genes, such as CYP19, the gene that encodes for aromatase, which is the target for the aromatase inhibitors (Anastrazole, Exemestane, and Letrozole). This type of work further provides the foundation for personalized medicine by identifying not just differences between the tumors, but also between what the individuals with cancers may have inherited from their parents. We hope this work will help us prevent exposing patients to unnecessary therapies.
I am involved in other biomarker studies to develop new ones in addition to estrogen and progesterone. These projects aim to identify people for whom chemotherapy does not work, so we can eliminate exposing them to unnecessary side effects. We are also developing new methods to test for potential clinical effects before we apply the intervention directly to patients. We are focused on devising new technologies to help us go forward.
Q: How close are we to preventing and curing all forms of breast cancer?
A: The overall mortality rate for breast cancer has dropped a great deal over the last 30 years. However, I think it is important to make the distinction among the different forms of breast cancer when we talk about "cure."
The majority of women with breast cancer today are diagnosed with hormone receptor positive disease; their breast cancer can be managed and even "cured" with existing therapies. Our challenges in treating these women are on how can we "cure" them more effectively while causing fewer negative side effects. More recently, anti-HER2 therapies have further reduced mortality in the small (~15%) group of women whose cancer makes an excess of HER2 protein.
For women with breast cancers that don't make these markers, so-called "triple negative" disease, our efforts are even more fundamental. We must first improve our understanding of what drives the growth of these tumors, so that we can develop more effective and less toxic therapies.
Q: In your opinion, how has BCRF impacted breast cancer research?
A: There are many examples of scientific advances that would not have happened without BCRF. In my own work, many of the NABCG activities mentioned above could not have happened without BCRF support. Groups like the NABCG give the overall cancer research community easy access to information and resources, which is vital to scientific progress. My pharmacogenomics project with Dr. Rae is critical to advancing personalized care, and BCRF funding has been instrumental in that too.
In addition, the pioneering work of people, such as Dr. Christine Ambrosone on breast cancer epidemiology and Dr. Edith Perez on treatment for HER2-positive breast cancer, were made possible by BCRF funding. My colleagues who study lung and gastrointestinal cancers often comment on how they wish for a private organization committed to scientific progress, like BCRF, in their fields.
Read more about Dr. Hayes' current research project funded by BCRF.