Women who carry the BRCA1 or BRCA2 genetic mutation are at high risk of getting breast cancer, but Israeli and American researchers have found they do not have a greater chance of dying from the disease than patients without them. Since some BRCA-related breast cancers occur earlier in life and can be resistant to common hormone treatments, researchers have wondered whether patients with the mutations might have a worse prognosis than others. With the new study, says Prof. Gad Rennert of the Technion-Israel Institute of Technology's Rappaport Medical Faculty, "we can offer the reassurance that in spite of a bad profile of prognostic factors in carriers, their survival is actually at least as good as for noncarriers." Rennert, Dr. Steven Narod of the University of Toronto and colleagues published their findings in the July 12 issue of the New England Journal of Medicine. They say their research could help women with BRCA mutations decide whether they want to undergo prophylactic (preemptive) removal of their breasts or continue with vigilant screenings to lessen their chances of developing cancer. The researchers used a unique set of medical records and tumor tissue samples from 1,545 Israeli women diagnosed with invasive breast cancer in the late 1980s. Among the Ashkenazi women in the study, two mutations of the BRCA1 gene and one BRCA2 mutation are especially prevalent. Since these women were diagnosed before the discovery of BRCA genes and received no special care as a result, Rennert and colleagues were able to compare their survival rates directly to those among patients who lacked the mutations. The study "can probably not be repeated with these advantages anywhere in the world, as Israel is the only place with such a high concentration of mutation carriers," Rennert said. The researchers looked at the women's survival rates 10 years after diagnosis and found that the prognosis was similar among those with a mutation and those without. Among the women who died within a decade, the average survival time was 37 months for women with a BRCA1 mutation, 48 months for those with a BRCA2 mutation and 46 months for those with no mutation. Chemotherapy apparently boosts the overall survival rates of patients with BRCA1 mutations, compared to survival rates among patients with no mutation; BRCA2 patients and patients with no mutation had similar survival rates, regardless of whether chemotherapy was part of their treatment. BRCA mutations can interfere with a cell's normal mechanisms for repairing damaged DNA, which may partially explain why chemotherapy had a different effect among BRCA1 patients, Rennert says. Chemotherapy's attacks on cancer cells may be more effective if these cells already have problems repairing damage, he said. "We definitely need to further evaluate the role of specific chemotherapy agents in BRCA carriers to be able to better offer specific chemotherapies to patients," Rennert said.