Chemotherapy may benefit all women with a BRCA1 mutation

Jul 12 2007

Breast cancer patients who possess one of the so-called "breast cancer" or BRCA genetic mutations do not have a higher risk of dying than patients with no BRCA mutations, according to a detailed study by researchers at the Technion-Israel Institute of Technology and the University of Toronto.

The findings are published in the July 12 issue of the New England Journal of Medicine.

Since some BRCA-related breast cancers occur earlier in life and can be resistant to common hormone treatments due to lack of hormone receptors in the tumor, researchers have wondered whether patients with the mutations might have a worse prognosis than others.

With the new study, “we can offer the reassurance that in spite of a bad profile of prognostic factors in carriers, their survival rate is actually at least as good as for noncarriers,” said Technion researcher Dr. Gad Rennert.

The researchers looked at 1,545 Israeli women's survival rates 10 years after diagnosis, and found that the prognosis was similar among those with a mutation and those without. Ten years later, 33 percent of non-carriers, 33 percent BRCA1 carriers and 44 percent of BRCA2 carriers had died.

Dr. Rennert and Dr. Steven Narod, Director of the Familial Breast Cancer Research Unit of Women's College Research Institute, Toronto, and their colleagues say their findings could help women with BRCA mutations decide whether to pursue surgery or continue with vigilant screenings to lessen their chances of developing cancer.

The researchers took advantage of 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 Jewish women of Ashkenazi descent in the study, two mutations of the BRCA1 gene and one BRCA2 mutation are especially prevalent.

However, since these women were diagnosed before the discovery of BRCA genes and received no special care as a result, the researchers were able to compare their survival rates directly to survival rates among patients without 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 noted.

Chemotherapy boosted 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.

“BRCA1 carriers seem in fact to be unusually sensitive to chemotherapy," said Narod. "These findings suggest that chemotherapy may benefit all women with a BRCA1 mutation, regardless of age or tumor size.”

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, according to Rennert. Chemotherapy's attacks on cancer cells may be more effective if these cells already have problems repairing damage, he explained.

“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.

The Technion-Israel Institute of Technology is Israel's leading science and technology university. Home to the country's winners of the Nobel Prize in science, it commands a worldwide reputation for its pioneering work in nanotechnology, computer science, biotechnology, water-resource management, materials engineering, aerospace and medicine. The majority of the founders and managers of Israel's high-tech companies are alumni. Based in New York City, the American Technion Society is the leading American organization supporting higher education in Israel, with 17 offices around the country.

http://www.ats.org/