This study investigated the question of whether women with close relatives who are BRCA1 or BRCA2 breast cancer mutation carriers and who themselves test negative for BRCA1 or BRCA2 mutations are at higher risk of breast cancer than the general population. The study included 375 U.S. women who were close relatives of known BRCA1 and BRCA2 mutation carriers and who were followed an average of five years after genetic testing. Study participants had a lower incidence of invasive breast cancer, but a higher incidence of in situ breast cancer than expected, based on National Cancer Institute statistics. Four invasive breast cancer were expected during the follow-up period, whereas two were diagnosed. There were two cases of in situ breast cancer whereas 0.9 cases were expected. None of the women developed ovarian cancer. The authors conclude that women without breast cancer who test negative for known familial mutations in BRCA1/2 should adhere to population-based guidelines for breast cancer screening.

Implications for breast cancer risk

The study findings support the advice often given to women who test negative for known BRCA1 and BRCA2 breast cancer gene mutations. However, two previous studies have found that such women are at higher risk for breast cancer than the general population and should be monitored more closely. One study found that in high-risk families, women who test negative for the familial BRCA1/BRCA2 mutation still have an increased risk of breast cancer consistent with observed genetic modifiers. A much larger study also found evidence that suggested that even relatives of breast cancer patients without BRCA1/BRCA2 mutations are at heightened risk for breast cancer (but not ovarian cancer) and that this risk appears to have a genetic component.