Ephrat Levy-Lahad, MD :: Profile
Director, Medical Genetics Institute
Shaare Zedek Medical Center
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 medical geneticist. My interest in breast cancer started fortuitously. I began my career as an internist with primary interest in adult diseases like Alzheimer's. At the time (the early 1990s), geneticists were mostly pediatricians. The idea that adult disease could also be related to genetics was new. Coincidentally, when I was doing a Medical Genetics fellowship at the University of Washington in Seattle, Mary-Claire King, PhD, the discoverer of BRCA1 (breast cancer susceptibility gene 1), just moved from University of California, Berkeley, to University of Washington. So I met with her, and we really hit it off.
After my training, I returned to Israel to set up a cancer genetics clinic, one of world's first, at Shaare Zedek Medical Center. There are genetic issues particularly relevant to Jewish women. For instance, mutations in the BRCA genes, which indicate predisposition to both breast and ovarian cancers, are found in a higher proportion of Ashkenazi Jewish women than any other group. Through the clinic, many basic science questions emerged. For example, why do women with genetic mutations get cancer? Also, when you look at women with the same genetic mutation, why do some get breast cancer in their 20s, while others in their 60s? Why do some develop ovarian cancer, while others will never get any cancer at all?
My colleagues and I also started thinking about prevention. We began to screen women systematically to identify ones at elevated risk so we could intervene clinically to prevent the development of cancer. Combining clinical practice with basic research has been very important. When I started my career, I did not think I would be doing much research but I really love it!
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: I currently participate in two BCRF-funded projects, one of which is a collaboration with fellow grantees Mary-Claire King, PhD (University of Washington) and Moien Kanaan, PhD (Bethlehem University). My main focus is using what is known about breast cancer genetics to improve prevention strategies.
In our Israel Breast Cancer Study, we evaluate BRCA1 and BRCA2 mutations in the Ashkenazi Jewish population of Israel. We tested over 8,000 healthy men and among them found 175 who were carriers of mutations. These men were the key to their families, because through them we could observe the cancer risk in their female relatives. We found that even when we identify a BRCA1 or BRCA2 family through a healthy male, women in the family who are carriers are still at elevated risk for breast and ovarian cancers compared to women without the mutation. We aim for how best to identify mutation carriers at the earliest point possible when prevention interventions are most effective. The patients we encounter in the clinic "inspired" this project. A normal 32 year-old woman would not think of herself as being at risk for breast cancer. But if you are a BRCA carrier, then your risk increases, and monitoring can mean a world of difference.
Our second project is a collaboration with Drs. Kanaan and King looking at breast cancer genetics in the Arab population. This project has two components. One is providing genetics services for the Palestinian population. Also, the Arab-Israeli population has not been studied extensively at all, so we are looking for new breast cancer genes.
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: Newly developed gene sequencing technology, allowing us to look at many genes at one time, helps us examine the interactions between genes, called epistasis. We are now entering the stage where we can look at 20,000 or 30, 000 genes at a time. The question that now arises is how to integrate all of this information, or data, to find a combination that tells us whether an individual is at increased risk and for what type of cancer.
Q: What direction(s)/trends do you see emerging in breast cancer research in the next 10 years?
A: From the genetics angle, the trend of better prediction of who is at risk will emerge so we will be able to do better genetic profiles. The other advance is the genetic profiling of the tumors themselves. Scientifically, for many years now, we know that breast cancer is not one disease but many diseases. At the molecular level, when you compare individual tumors and the genes are expressed in them, we can put them in subgroups or subtypes. We already know that tumors are different in their biological behaviors and responses to treatment; this subtyping will become very sophisticated in the near future. This is also a component of what is called "personalized medicine." When you look at cancer, it has two prongs - one is your own genetic background or make-up and the other is that of the tumor, and the interaction between these two, which extends to response to treatment. The hope is that if you understand so much more about the genetic biology of the tumor, you'll have many more specific drugs that will combat it.
Q: What other projects are you currently working on?
A: Most of my other work is not related to cancer but does come out of the collaboration with Dr. Kanaan. In the Middle East, pediatric hereditary diseases are prevalent because of consanguinity and because families tend to be large. We are very interested in finding the genetic basis of diseases such as microcephaly, mental retardation, and endocrine disorders, with our topmost goal being prevention. Building on the work started with BCRF, we just received a large grant from Middle East Regional Cooperation (MERC) Program through USAID to do this research.
Q: How close are we to preventing and curing all forms of breast cancer?
A: I think we're closer than we think. In terms of prevention, genetics holds huge promise in this regard. I can envision a not too distant future where we can understand most of the genetic predispositions to cancer. Even though I am a geneticist, I know that not everything is genetic. So there will be other risk factors, but understanding what's genetic will allow you to weed out what is genetic and what is not. Even now when you look at treatment of breast cancer, there has been tremendous progress. I think it will happen at a much faster pace again because we'll understand more of the biology. I think it's a combination of prevention, early detection, and treatment. All of that comes together.
Q: In your opinion, how has BCRF impacted breast cancer research?
A:I don't think I could have done breast cancer research without BCRF. I work in a part of the world where the funding for research does not come close to what's available in the US or Europe. Technically, all of the work that we've done would have been impossible without BCRF. BCRF has been the difference between being able to do research and not being able to do it.
Also, BCRF gives researchers the freedom to think about what they'd really like to do, try out new ideas. When we started our study on healthy people and checking them for BRCA1 and BRCA2, I would say that many of my colleagues thought we were "really pushing the envelope."
Finally, as a person, I think medicine and science are areas where the "human good" and the common goals are so obvious that it becomes easier to overcome some of the obstacles often associated with political conflict, like the Israeli/Palestinian situation. Our projects funded by BCRF give people the opportunity to work and spend time together whereas otherwise they never would have had the chance. For example, BCRF supports a Palestinian PhD student, who works both in Bethlehem University and at Shaare Zedek. We have common goals, and this collaboration transcends borders that are not often crossed. We are very proud of sustaining this joint effort and are thankful to BCRF for inspiring it. That has had a big impact.
Read more about Dr. Levy-Ladad's current research project funded by BCRF.