Ephrat Levy-Lahad, MD

2012-2013 BCRF Projects:
1) The Roz and Les Goldstein Award
The Israeli Breast Cancer Study

Co-Investigators: Mary-Claire King, PhD, University of Washington, Seattle, WA and Moien Kanaan, PhD, Bethlehem University, Palestinian Authority

Drs. King, Levy-Lahad, and Kanaan have now enrolled over 640 breast cancer patients of Palestinian origin in their studies. They found mutations in known breast cancer genes in 8/48 (17%) patients who were analyzed for all known cancer genes. This high proportion is consistent with the team's hypothesis that since breast cancer is less frequent in the Palestinian population, a larger proportion of cases will be due to an inherited predisposition. They will now be analyzing all known breast cancer genes in an additional 176 cases with family history. They expect to identify new mutations, and in cases where no mutations in known genes are identified, they will search for novel breast cancer genes.

Mid-year Progress: This research team has now enrolled over 700 breast cancer patients of Palestinian origin and has begun their analysis by next generation sequencing. In the first 48 patients evaluated, they found inherited cancer-predisposing mutations in 17% of patients, in BRCA1, BRCA2, and four other genes. This proportion of patients harboring damaging mutations is among the highest seen in any population. It is consistent with the team's hypothesis that since breast cancer is less frequent and occurs in younger women in the Palestinian population, a larger proportion of cases will be due to inherited predisposition. They will analyze all known breast cancer genes in an additional 200 cases with family history or young age at diagnosis. The investigators expect to identify new mutations, and in cases where no mutations in known genes are identified, they will search for novel breast cancer genes.

2) In a previous BCRF-supported study, Dr. Levy-Lahad's team found that BRCA1/BRCA2 carriers identified at random in the general Ashkenazi Jewish population have high risks for breast and ovarian cancer. This is true even though there is little cancer history in over half of carrier families. Based on these findings, Dr. Levy-Lahad's team believes screening for BRCA1 and BRCA2 mutations in the general Ashkenazi Jewish population — not just individuals with family history of cancer — is justified in order to identify women at risk. These women can undertake early detection and prevention measures that have been shown to save lives.

Screening the general population for genetic cancer risk has never been done before. The Ashkenazi Jewish population is a model in this respect, because of a high frequency of common mutations. However, with advances in genetic testing technology Dr. Levy-Lahad's results could be extrapolated to any population. This team has started a population screening project, in which testing for common BRCA1 and BRCA2 mutations is offered to all healthy Ashkenazi Jews, regardless of their family history. They are enrolling both men and women and are comparing different screening strategies in order to determine the best way to offer BRCA1/BRCA2 screening to the general population.

Dr. Levy-Lahad's team has so far enrolled over 680 persons, and identified 12 carriers among the first 674 tested. Half of these carriers did not have significant family history and would not have been identified if not for a general screening program. Data from questionnaires filled by participants indicate that 90% are satisfied with the screening process, which does not include traditional genetic counseling prior to testing, and that 95% were satisfied with the decision to be tested. There was no indication for adverse short-term emotional effects.

Mid-year Progress:To date, Dr. Levy-Lahad's team has more than doubled recruitment and has now enrolled over 1,500 people to their study. Among the first 1,300 in whom testing has been completed, 26 carriers were identified. One-third of these carriers did not have significant family history and would not have been identified if not for a general screening program.

Dr. Levy-Lahad's new data indicates that uptake rate for testing, that is the percentage of people offered testing who agree to be tested, is 59 percent. Their initial analysis indicates that the decision to be tested is not influenced by having children or daughters, and that older persons (70 years and older) are less interested in testing. This suggests that the main impetus for testing is personal cancer risk assessment for planning future surveillance and prevention measures. Data from questionnaires filled by participants indicate that 90% are satisfied with the screening process, which does not include traditional genetic counseling prior to testing. About 95% were satisfied with the decision to be tested. There was no indication for adverse short-term emotional effects.

Bio:
Ephrat Levy-Lahad, MD, is Professor of Internal Medicine at Hebrew University and, since 1996, Director of the Medical Genetics Institute at Shaare Zedek Medical Center in Jerusalem. Dr. Levy-Lahad is one of the world's foremost authorities on inherited breast cancer among Jewish women. She directs the Israel Breast Cancer Study (IBCS), the sister project of the New York Breast Cancer Study (NYBCS), which is directed by Mary-Claire King and Joan Marks; both projects are sponsored by The Breast Cancer Research Foundation.

The IBCS asks the question: Should genetic testing of BRCA1 and BRCA2 be offered, on a voluntary basis and without cost, to all Ashkenazi Jewish women in Israel? Does clinical evidence support this option? In addition to her work on inherited breast cancer among Jewish women, Dr. Levy-Lahad initiated, in partnership with Dr. Moien Kanaan of Bethlehem University and fully supported by BCRF, a highly successful effort to bring cancer genetics services to underserved Arab Israeli and Palestinian women.

Dr. Levy-Lahad received her medical degree from the Hebrew University-Hadassah Medical School in Jerusalem, Israel. She then completed a residency in Internal Medicine at Shaare Zedek Medical Center in Jerusalem, and a three-year fellowship in Medical Genetics at the University of Washington in Seattle. Since 1996, when she returned to Israel, she has been Director of the Medical Genetics Institute and senior physician in the Department of Medicine at Shaare Zedek Medical Center. Dr. Levy-Lahad holds a faculty appointment as Associate Professor in Medicine and Genetics at the Hebrew University-Hadassah Medical School in Jerusalem.

In April 2012, Dr. Levy-Lahad was appointed co-chair of Israel's National Bioethics Council. She also currently serves on the International Bioethics Committee of UNESCO and chaired that committee's development of guidelines for stem cell research. She was recently named one of "Israel's Best Doctors."