Cancer Research Lab

New research indicates that there is considerable variation in the risk of breast cancer among carriers of BRCA1/2 mutations.

“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 the women with contralateral breast cancer had higher (though not significantly higher) risks than relatives of women with a single breast cancer.”

“Although previous studies have not addressed this issue directly,” Dr. 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 for January 9/16, the researchers analyzed data from 1394 women with unilateral breast cancer and 704 with contralateral breast cancer who were enrolled in the Women’s Environmental Cancer and Radiation Epidemiology (WECARE) study. All of the subjects were genotyped for mutations in BRCA1 and BRCA2.

Overall, 73 patients (5.2%) with unilateral breast cancer had a BRCA mutation, including 42 with BRCA1 and 31 with a BRCA2 mutation. In the contralateral cancer group, 108 (15.3%) had a BRCA mutation, including 67 with a BRCA1 and 41 with a BRCA2 mutation.

A younger age at diagnosis in the proband significantly increased the risk of breast cancer in relatives of carriers (p = 0.04). In addition, the risk of breast cancer tended to be higher for relatives of contralateral rather than unilateral breast cancer patients. Lastly, significant differences in risk were seen between carrier families after accounting for the observed characteristics.

Dr. 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.”