Judy E. Garber, MD, MPH :: Profile
Director, Center for Cancer Genetics & Prevention
Dana-Farber Cancer Institute
Associate Professor of Medicine
Harvard Medical School
Member, BCRF Scientific Advisory Committee
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?
My mother had breast cancer when I was in the fifth grade. She survived for 40 years despite having had positive nodes, so we can't complain about her radical mastectomy and lymphedema, but I became interested in cancer from that experience.
As I went through school, I realized that I really enjoyed science more than other subjects. Although I've always wanted to be a doctor, along the way I began to think about "doing more," so I started medical school with the intention of entering health administration. However, the summer after my first year, I was offered a position at the National Cancer Institute (NCI) to study epidemiology, looking at patterns of cancer in families. Although this took place before any "formal" cancer genetics program had been established, there were clearly families who had cancers clustered in them, and that fascinated me. This experience convinced me that I wanted to focus on research and I�ve never looked back.
Today, I am a clinical cancer geneticist and a breast oncologist. My research focus is on identifying individuals at highest risk for breast cancer and helping them prevent the disease. I collaborate with other scientists to try to understand whether treatment should be different for people with inherited risk.
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: In our previous BCRF-funded work, we had learned quite a bit about BRCA1. With Dr. David Livingston at Dana-Farber, another BCRF grantee, we were able to do a clinical trial with cisplatin, a drug that targets a specific defect in BRCA 1 function. My group has also worked with other BCRF investigators, Drs. Stuart Schnitt and Nadine Tung at Beth Israel Deaconess and Andrea Richardson at Brigham and Women's Hospital, on triple-negative breast cancer, to see how frequently BRCA1 was mutated in those individuals. These studies have allowed us to say conclusively that individuals with triple-negative breast cancer often have a mutation in their BRCA1 gene.
Our project this year is focused on BRCA2, which is a much bigger gene than BRCA1 and one that leads to estrogen receptor-positive (ER+) and HER2-negative tumors, the most common tumor type. At first examination, BRCA2 tumors look just like other hormone receptor positive, HER2 negative tumors. There is evidence, however, that at the molecular level, they share some important features with BRCA1-related tumors - not a surprise, since the two genes are active in the same pathway of DNA repair. Finding ways to distinguish the BRCA2 tumors from the other ER+, progesterone receptor-positive (PR+), HER2 negative tumors, which comprise about 60% of all breast cancers, has been challenging. We have some new ideas about the cells from which the BRCA2 cancers may arise that may help us find the specific features of the BRCA2 cancers so we can distinguish them more easily
Our primary goals are twofold: first, being able to characterize features of BRCA2 tumors that would help us distinguish them from among the larger group of tumors that are hormone sensitive; and second, looking at the molecular characterizations of these tumors, we want to look for particular vulnerabilities that we can exploit clinically. Because they are hormone receptor positive, some aspects of the treatment of BRCA2 tumors will be different from BRCA1-associated tumors. Options for prevention may also be different. For example, there are some data that tamoxifen can reduce the risk of BRCA2 tumors. However, some of the BRCA2 tumors, despite their hormone receptors, do not behave like other hormone receptor- positive tumors, and these require different treatment. Moreover, if the basis for the development of BRCA2 tumors is the "BRCA2-ness" more than the hormonal issues, then it makes sense that both the treatment and prevention strategies for them should be different from other hormone-associated breast cancers. But, first, we have to be able to find them easily and reliably. This is why we are focusing on BRCA 2, so we will be able to offer the same kinds of advances to these women as we have been able to for women with BRCA1 mutations.
Q: Are there specific scientific developments and/or technologies that have made your work possible? What additional advancements can help to enhance your progress?
A: Several things happened closely together. First, Dr. Mary-Claire King, another BCRF investigator, identified or mapped the gene for breast and ovarian cancer (BRCA1) the same year that my group, working with Dr. Frederick Li at Dana-Farber, found that the tumor supressor gene p53 was instrumental in the development of the Li-Fraumeni syndrome, named after Dr. Li. Then, the BRCA2 and the colon cancer genes were mapped very quickly afterwards. So, suddenly we went from one gene that might explain cancer in families to four, and two of them involved breast cancer.
Since then, researchers have learned to sequence genes and do microarrays looking at many genes at once. They've learned how to process samples so you can easily store them, retrieve them, and study them. These novel technologies made it possible for us to look at genes more systematically, see more of them at once, and find more relationships that we didn�t realize existed before. All of these developments help facilitate our work in genetics.
Also, Dr. Livingston's work on how BRCA1 works in DNA repair made my group think about treatments and changing them to target the specific weakness that BRCA1 causes. When I first started out, it wasn't possible even to imagine being able to do things, such as finding genes, understanding their functions, and then trying to target their errors. This is an amazing time to be working in cancer genetics, when the possibilities seem to be unfolding all the time.
Q: What direction(s)/trends do you see emerging in breast cancer research in the next ten years?
A: I think that we will be able to move even faster now that we understand more about the different subtypes of breast cancer. We now can think about targeting therapies for those particular genes and learning how to combine these targets - one at a time has already been shown to be insufficient.
For my own work, I hope that we will be able to exploit the targeted approach on the prevention side as well. We see many people at risk and we need to be able to offer them more than just screening or tamoxifen. We can see those developments coming along too. Finally, I think we have to learn more about lifestyle factors. Some of the work that BCRF supports is in the direction of helping people find a way to stay well and avoid cancer, along with other health problems. I think there is progress in that area too. So, I'm hopeful.
Q: What other projects are you currently working on?
A: My group is also trying to understand the effectiveness of neo-adjuvant, or pre-surgical, therapies in breast cancers, through a project with Dr. William Kaelin (Dana-Farber), another BCRF investigator. In addition, we are looking at another target in breast cancer, particularly at the breast cancers that develop in individuals with the Li-Fraumeni syndrome. After all these years, we return again to Li-Fraumeni because we have some new clues that may help us to recognize them better and try to deal with those and in people who are at high risk for cancer.
At Dana-Farber we are working on a bigger "personalized medicine" platform looking at people's genes - in their tumors as well as those they are born with - not just their cancer susceptibility genes but also those that are important in metabolizing drugs and affect treatment responses which may help us to "individualize" therapies more effectively for each patient.
Also, I was recently inaugurated President of the American Association for Cancer Research (AACR) for the upcoming year. Planning for next year's AACR meeting and the San Antonio Breast Cancer Symposium will take up a fair amount of my time.
Q: How close are we to preventing and curing all forms of breast cancer?
A: Not close enough! We have certainly made progress in the last 10 or 20 years but we have a long way to go. Although we have succeeded in often making breast cancer a disease that can be "cured" or managed over a very long time, for every woman who gets breast cancer and isn't cured, that's just not enough. There is no doubt that we have made progress, but we are still a while away from "curing" every single person with breast cancer. Progress will continue to be constant� as long as we have funding.
Q: In your opinion, how has BCRF impacted breast cancer research?
A: Several of my projects would not have come about without BCRF. From my group's point of view, some of the most important projects we've done, such as the work on platinum, really began because we got some seed money from BCRF. Without that seed money, we never would have been able to work on the prevalence of mutations in triple-negative breast cancer or our current project on Li-Fraumeni. Every researcher will tell you that seed money is the hardest to come by, even though it is critical to moving forward. That's absolute.
Quite a few of my projects even started at BCRF's faculty retreat. When we researchers get together and have the chance to "talk science" or about projects, things happen. I think many BCRF investigators have stories like this.
Furthermore, BCRF has made very important contributions to breast cancer because of the novelty of its funding approach. BCRF funds researchers and ideas; they don't fund projects. That is a very different approach. Nobody else does this. It is an unusual way to fund cancer research but it�s investing in people whom BCRF�s Scientific Advisors feel have proven themselves as people who make contributions. They are helping that to continue. I think this model and the consistency of BCRF support from year to year have allowed the Foundation to have an impact far beyond what you might have expected from an organization of its size. We are tremendously grateful to BCRF!
Read more about Dr. Garber's current research project funded by BCRF.