Breast cancer risk varies widely in BRCA carriers

January 8, 2008

NEW YORK (Reuters Health) - New research indicates there is considerable variation in the risk of breast cancer among carriers of BRCA1/2 mutations, which are known to increase the risk of breast cancer.

"The major finding is that the risk appears to vary," lead author Dr. Colin B. Begg told Reuters Health. For example, relatives of carriers diagnosed at young ages have higher risks than relatives of carriers diagnosed at older ages." Also, relatives of women who develop cancer in both breasts tended to have higher - but not statistically significant higher -- risks than relatives of carriers with breast cancer in one breast.

"Although previous studies have not addressed this issue directly," Begg, from Memorial Sloan-Kettering Cancer Center in New York, added: "the literature shows a wide range of risk estimates, and in particular much higher risk estimates have been found in studies that use families with multiple cases of breast cancer than in population-based studies like ours."

As reported in the Journal of the American Medical Association, the researchers analyzed data from 1,394 women with cancer in one breast and 704 with cancer in both breasts who were enrolled in the Women's Environmental Cancer and Radiation Epidemiology study. All of the subjects underwent genotyping to detect BRCA1 and BRCA2 mutations.

The National Cancer Institute estimates that between 5 and 10 percent of women in the general population carry a BRCA mutation. In general, there is no significant difference in prevalence according to race or ethnicity, with the exception of Ashkenazi Jews (Eastern European) who have a higher prevalence.

Overall, 73 patients (5.2 percent) with cancer in one breast had a BRCA mutation, including 42 with a BRCA1 and 31 with a BRCA2 mutation. In the group with cancer in both breasts, 108 (15.3 percent) had a BRCA mutation, including 67 with a BRCA1 and 41 with a BRCA2 mutation.

A younger age at diagnosis significantly increased the breast cancer risk among relatives of carriers. In addition, the risk of breast cancer tended to be higher for relatives of carriers with cancer in both breasts. Lastly, significant differences in risk were seen among the carrier families.

Begg commented that "there are lots of distinct mutations within the BRCA1 and BRCA2 genes. Most of these are individually rare. An important question is the extent to which risk varies depending on which of these mutations is present in the carrier. We (and others) are currently studying this issue."