Dr. Suzanne Fuqua is a Professor of Medicine and Molecular and Cellular Biology at Baylor College of Medicine. Her research focuses on understanding the role of somatic (non-inherited) mutations in the estrogen receptor gene (ESR1) in resistance to anti-hormone therapies. Dr. Fuqua was the first to discover a modification to ESR1 in breast tumors that affects many aspects of hormone action and response to anti-estrogen therapies, such as tamoxifen and aromatase inhibitors. Her team discovered a mutation called Y537N that has been shown to promote drug resistance and metastasis. A major goal of her laboratory is to develop new ways to target these alterations in ESR1 and identify other novel mechanisms of resistance. BCRF recently spoke to Dr. Fuqua about her research and the future of breast cancer.
BCRF: What inspired you to pursue a career in breast cancer research?
SF: I’ve been interested in cancer research since high school (and actually found some papers I wrote in high school in my mother’s attic). But it wasn’t until I was working on my PhD at MD Anderson that I got the inspiration I was looking for.
I heard a talk by Bill McGuire who believed that the only way we would cure breast cancer would be through multidisciplinary research. He was assembling a team of researchers including biologists (which is what I was), clinicians, pathologists, biostatisticians, etc. I knew at that moment he was the person I wanted to work with and that curing breast cancer was the goal of my life.
The late William L McGuire, MD, was a physician scientist and a founder of the SABCS, where an annual distinguished lecture named for him is given each year.
BCRF: So it was the motivation of being part of a multidisciplinary team to attack the problem?
SF: This was the beginning of genomics and microbiology, which really exposed how big the problem was and forced the realization that we needed teams of scientists to tackle the problem–that no one was going to do it by working alone in a laboratory.
BCRF: What drives you every day to do the work you do?
SF: I want to help people. I think my research and the discoveries I’ve made have accomplished that.
BCRF: In that regard, what do you think is your most significant contribution?
SF: My most significant contribution was the identification of the mutations in the estrogen receptor gene (ESR1), first in metastatic breast cancer and more recently in primary breast cancers, which I think we will be able to use as a marker to guide hormonal therapy. This discovery was not originally accepted by the research community. Due to limitations of the technology at the time (more than 15 years ago) our finding was difficult to confirm by other groups. But I championed the idea, because I truly believed that it would help women with breast cancer. After 15 years of perseverance, other laboratories have now validated the ESR1 mutations in metastatic disease. I think my most significant scientific contribution is sticking with this work until the technology caught up to where our original findings could be verified by other groups.
BCRF: While we’re on the subject of ESR1, tell us more about your BCRF project.
SF: My team’s BCRF project is focused on validating that the ESR1 mutations we found in metastatic breast cancer also occur in primary breast tumors. This is still considered controversial. I am collaborating with other investigators in the U.S. and Europe to share samples from their clinical trials so that I can measure ESR1 mutations in primary tumors and correlate that information with treatment outcomes. We can then design a clinical trial, an idea which has already generated serious interest among my colleagues and collaborators. With BCRF support, we will be able to quickly translate our discovery to a real difference in patient care. We’re also looking at other ESR1 mutations that may be clinically important, and trying to answer the question as to why these mutated cells remain dormant for so long, as is the case with late recurrence (more than 10 years after diagnosis). Our BCRF funding came at the perfect time to take advantage of some new collaborations and new technology that will allow us to answer some of these puzzling questions.
BCRF: What do you think makes BCRF unique and why is our funding model so important to advancing the field?
SF: The reality is that the majority of funded research is “safe” science, meaning that much of the science is already done before the application for funding is submitted. And safe science is not likely to lead to the breakthroughs that we need to cure breast cancer.
It is almost impossible to do high-risk projects through traditional funding mechanisms. Not only do we risk losing ground on new therapies, because scientists can’t get the funding to do the forefront science, but we risk losing the next generation of scientists because of the lack of funding.
Other countries are ahead of us in funding research and the U.S. risks losing the opportunities of promising breakthroughs in healthcare. The technology is moving so quickly, if we don’t take advantage of it we’ll fall behind.
The main thing to remember is, we wouldn’t be where we are today if all we did was safe science. BCRF is keeping that thought alive and ensuring that the scientists who are positioned to advance the field have the resources and freedom to do the high-risk/high-reward types of research.
BCRF: What do you think are the major scientific challenges that need to be addressed in order for us to cure and ultimately prevent breast cancer?
SF: We can’t beat the beast until we know the beast and we can’t know breast cancer until we understand metastatic disease. For so long we approached breast cancer based on the primary tumor. In other words, if we know the primary tumor we will know what to do if the cancer comes back. Now we know that there could be factors that drive metastasis that weren’t in the primary tumor. The scientific breakthrough we need will come from biopsies of the metastatic tumor, treating metastasis as a separate disease and targeting the changes that have occurred.
In 2013, BCRF committed $27 million to launch the Evelyn H. Lauder Founder’s Fund, an international, multi-year collaboration focused on dissecting the molecular basis of metastasis.
We’re in the infancy of that field, but we’ve made progress in identifying what we can target in the metastatic tumor. The most important example of that is the validation and rediscovery of ESR1 mutations in metastatic disease, which is going to help the majority of women with estrogen receptor-positive breast cancer, the most common type of the disease.
BCRF: What do you think is going to be the next major breakthrough in breast cancer?
SF: I hope it’s going to be making genomic analyses affordable for everyone. I recognize that there are other barriers to genomic analysis besides cost. Research has identified hundreds of mutations that we don’t yet understand and for which we don’t have targeted therapies. I agree that how we handle that information in terms of patient counseling and treatment is a challenge, but I believe that preclinical research will make those ambiguous mutations actionable. Because we didn’t know they were there, we haven’t done the research to understand what they mean. As we discover more and more mutations, we can combine genomic tools with preclinical research to find the appropriate therapy for a specific mutation in a metastatic breast cancer. I think that is probably the next breakthrough.
BCRF: Do you see a cure for breast cancer?
SF: I see breast cancer as a manageable disease with targeted combination therapies. I like to use a whack-a-mole analogy, where you knock down one tumor protein or pathway and another one pops up–and the tumor continue to grow in spite of your efforts. In breast cancer we know that when we knock down one pathway with a targeted drug, multiple “moles” pop up. A cure means whacking multiple moles at once with combination therapies, and genomics will help us know where the next whack-a-mole is (in other words, what targets to hit). The hope I have is that the combination of liquid biopsy techniques with proteomics (the study of the proteins) will take us to where we can even more accurately identify and target the tumor whack-a-moles.
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