BCRF sat down with Dr. Laura Esserman to discuss her 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.
A: I was always interested in the science and the biology of cancer. I'm also a people person! I realized early on that while you may not be able to alter biology, you make a difference every day in clinical medicine. You can alter the experience of the person; caring always makes a difference. What drew me specifically to the field of breast cancer was my experience as a post-doctoral fellow in Ron Levy's laboratory at Stanford University - his lab was taking what I thought were the most innovative approaches to treatments, developing targeted, less toxic therapies based on biology. He happened to be concentrating on lymphoma, which isn't a surgical disease, and I was a surgery fellow so I wanted to focus on a different type of cancer. I also knew that women with breast cancer were frustrated with the kind of care they were getting and with the treatment options. I decided that instead of taking care of many areas of disease, I was going to take care of one: breast cancer.
Q: You have an MBA as well as a PhD and an MD. How has having an MBA helped or altered your experience as a surgeon and researcher?
A: Getting my MBA helped me figure out how I was going to put it all together. Before I even got to that point, however, I paid my way through medical school by working as a research assistant for David Eddy, a mathematician and surgeon known for his modeling of health care delivery and performance. From Eddy's health policy analyses, I learned that managing cancer is all about the understanding the disease biology, and specifically, how to screen effectively for all the different types of cancer. I also learned that good medical care is about coming up with creative options for people based on the disease they have, not the disease medicine has figured out how to treat.
After medical school I was recruited to business school by Alain Enthoven who is known for his work on organized systems for competing on quality modern management techniques. A lot of physicians don't regard management as a science; Enthoven encouraged me to apply management expertise to medicine. Management science works very well in breast cancer treatment. Once I finished the MBA, the next step was to put together a center that would cater to patients' needs. It replaces the model of a center for research OR a center for patient care. We should no longer have centers where it's either/or. And to measure the quality, every year you should be able to do things better than you did the year before. The new model is to build systems that allow you to tailor care to patients' biology, patient preferences, and according to performance of the clinical interventions, with women involved in every stage of the decision-making.
In addition to the center I direct in San Francisco, I organize and run a lot of very big, multi-center studies. In business school I learned about teamwork - specifically how important teamwork is in medicine and in research. We need to become better at working together and overcoming barriers. I can show people how to do that through good management.
Q: You are known for your discovery that a kind of immune system cell - called a proliferating macrophage, or ProMac - hangs out in the same environment where there are certain kinds of aggressive cancer cells. Can you tell us more about this discovery and how it can help prevent and treat certain breast cancers?
A: This is a discovery based on working your way backwards from the cancer to the screening technology. For some cancers, we have very little to work with in terms of screening. I was looking at fast-growing breast cancers and asking myself: is there something in there that we can see and target, even if it is not causing the cancer? That's where these ProMacs come in. They are part of the immune system's interaction with the breast tissues in the presence of these high-grade, aggressive cancers. We can find the ProMacs, and when we do, we know to start looking for that type of breast cancer. We don't have anything that prevents these cancers - screening is not prevention - but if we can start to anticipate them better, we can strategize how to treat them better, by disrupting the environment that supports their growth. If that works and we can sort out who is at risk for these cancers, maybe we can work on preventing them.
Q: Could you describe your recent research on statins, a class of drugs known for treating cholesterol and heart disease, and what role they may play in preventing cancer?
A: I had proposed testing statins, which are known, safe drugs for treating high cholesterol, because we had seen that some of them can inhibit cancer cells. Our initial hypothesis was that statins might be particularly effective as a tumor prevention for women with DCIS who are at risk for developing aggressive, ER-negative tumors. These are the types of tumors that we have fewer treatments for, and poorer outcomes. Unfortunately, the National Cancer Institute turned down my initial request for funding, saying that there wasn't enough evidence to support my hypothesis. BCRF stepped in with funding for a pilot trial and in the process we learned a lot. Turns out it's really only the high-grade tumors that are affected by statins, not the low-grade DCIS. That's okay! That's important to know! Based on this study, we learned more about the biology of these ER-negative tumors and really developed a cool new concept. We are studying "nesting" statins in as a treatment before surgery to see if they will inhibit tumors before we remove them. This may reduce the time it takes us to learn which agents work for prevention and help us realize better outcomes for our patients.
I often think about an article that Intel founder Andy Grove published in the Journal of the American Medical Association in 2005, called "A View from the Outside." It is apropos in terms of how we should be thinking. Grove challenged us to consider whether we really want our "knowledge turn" to be 20 years - that is, 20 years from the spark of a new idea to a resulting safe and effective treatment. He asked whether it is too risky to do something different, or whether the real risk is not to push for more rapid change. My feeling is that we should constantly try to turn the existing model on its ear - 20 years is too long from my perspective and though the alternatives may not be perfect, it is so important to look for all opportunities to accelerate learning for the prevention of breast cancer!
Q: How can laypeople better understand the significance of statins and macrophages as surrogate markers for breast cancer outcomes?
A: All cancers, and breast cancer is no different, can be likened to a bunch of criminals. Some commit petty crimes and some are killers. We try to understand the criminals, especially the bad ones-that is, the tumors, but we also must take advantage of understanding the "neighborhoods" where the criminals hang out. In other words, where are these criminals hanging out and with whom? This is exactly the right analogy for how we found the immune system cells called ProMacs. They show up consistently in the same vicinity with a certain type of fast-growing breast cancer. So our strategy is to try to clean up the neighborhood to prevent a crime.
Q: How close do you think we are to preventing or finding a cure for breast cancer?
A: When we are willing to get more into the details of particular cancers, we will make better progress. If you are at risk for an ER-negative breast cancer, for example, you can't use the screening strategies in place for ER-positive tumors. This is partly why ER-negative breast cancer outcomes have been so poor. We've been using inappropriate screening strategies. We need a different strategy or strategies based on the details of the kinds of cancer that present as large masses between normal screens - so-called interval cancers. That is what I have been working on. Our challenges are in clarifying the risks for some of these less understood breast cancers and then figuring out what things we can do to either prevent them or detect them earlier.
Also, we need to learn how to tailor treatment to the biology of the particular breast cancer and to the patient. Cancer doesn't happen to a body part; it happens to a person.
Q: How has BCRF been helpful to you?
A: BCRF rewards people for being thoughtful and it helps overcome a lot of barriers. My colleague Funmi Olapade took our macrophage study and validated it in a patient population in her work with patients in Africa who need better screening for their particular type of breast cancer. BCRF allowed me to do one arm of this research that I thought was important and allowed Funmi to do the other arm of it. Both are necessary and now we are publishing our results together. Creative ideas can die without the proper support and BCRF gives resources to people with creative ideas and lets them do what they think is important.
BCRF's legacy thus far is as an incubator. They help grow innovative ideas in a similar way that small biotech firms incubate ideas and make rapid progress on them before the heftier process of pharmaceutical companies get involved. It's important in the non-commercial sectors of medicine that people know there is a funding outlet for what they do and that they will be rewarded for being thoughtful.
Q: What are the biggest challenges in cancer research?
A: That's easy: unbelievably inefficient systems for the collection of information. We need better systems for getting data collected correctly once and then shared forever.
Another challenge is making sure that we are communicating what the real problems and issues are in breast cancer prevention, screening and treatment. Without proper identification and communication of the needs and challenges of the field we are going to move unnecessarily slowly.
Q: What advice would you give to young researchers entering the cancer research field?
A: Passion and perseverance are key! I feel privileged to do what I'm doing every day. Patients sense when you truly care about them. To be successful in clinical medicine you must become an advocate for your patient, not for your research or your specialty. Do I get frustrated when patients don't do well? Of course, but research is a good antidote for the frustrations of clinical medicine.
As far as research is concerned, good ideas are abundant, but people who can turn those ideas into something in the end win the day. Collaboration and long term gains are much better than solo personal accomplishment in research. I hope we can change our ways of promoting people and consistently reward them for collaborating. The bottom line: making a difference in a patient's life is much more important than any publication.
Read more about Dr. Esserman's current research project funded by BCRF.