Women who don’t carry their family’s BRCA1 or BRCA2 mutation showed no increase in breast cancer risk in a study of 3,047 population-based families reported online Oct. 31 in the Journal of Clinical Oncology.
"These results support the standard clinical practice of advising noncarriers that they do not have any increase in breast cancer risk attributable to the family-specific BRCA mutation and, in the absence of other strong risk factors, should follow general population guidelines for breast cancer screening," said Dr. Allison W. Kurian of Stanford (Calif.) University and her associates.
Some recent studies have suggested that noncarriers of a family-specific mutation may have a two- to fivefold increase in risk of developing breast cancer, compared with the general population. While lower than the 5- to 20-fold increase in risk for carriers of the mutation, this rate would still be high enough to warrant breast cancer surveillance. Other studies have found no increase in risk among noncarriers.
To clarify the issue, Dr. Kurian and her colleagues assessed breast cancer risk using population-based cancer registries in the United States, Australia, and Canada. They identified 3,047 families in which one woman (the proband) was diagnosed as having breast cancer at a relatively young age, in most cases during 1996-2000, and she and her female first-degree relatives underwent genetic testing for BRCA1 and BRCA2 mutations.
Women in all three countries showed a similar prevalence of the mutations, similar rates of breast and ovarian cancer, and similar ages of onset for the malignancies. Overall, 160 families had BRCA1 mutations and 132 had BRCA2 mutations, the investigators reported (J. Clin. Oncol. 2011 Oct. 31 [doi:10.1200.JCO.2010.34.4440]).
Among noncarriers of family-specific mutations, the risk of developing breast cancer was not significantly higher than the risk among women in families without any BRCA1 or BRCA2 mutations. This relative risk was 0.39.
It is possible that previous studies reporting an increased risk in noncarriers have overestimated this risk, because they compared study subjects with women in the general population rather than women whose relatives have breast cancer. The latter group undergoes more frequent screening and consequently has more frequent diagnoses of breast cancer than women in the general population, Dr. Kurian and her associates noted.
Their study, in which 292 families with BRCA1 or BRCA2 mutations were compared with 2,755 families without such mutations from the same populations, "represents the largest analysis to date of breast cancer risk to noncarriers of family-specific mutations," they added.
The study was supported by the National Cancer Institute, the National Institutes of Health, Cancer Care Ontario, Cancer Prevention Institute of California, and the University of Melbourne. No financial conflicts of interest were reported.