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Women with a significant family history of breast cancer but no BRCA mutation are four times more likely to develop breast cancer than women in the general population. These results were presented at the American Association for Cancer Research’s Seventh Annual International Conference in Washington, D.C. on November 17, 2008.[1]

Breast cancer is the second leading cause of cancer death in women in the United States, with approximately 180,000 cases diagnosed each year. Progress in the areas of screening and treatment has allowed for earlier detection and higher cure rates. Researchers continue to study the incidence rates and patterns of this disease with the hopes of further improving screening, prevention, and treatment.

Inherited mutations in two genes-BRCA1 and BRCA2-have been found to greatly increase the lifetime risk of breast and ovarian cancer in women. Mutations in these genes can be passed down through either the mother’s or the father’s side of the family. Women with BRCA mutations have an 85% lifetime risk of developing breast cancer and typically undergo more vigilant screening, chemoprevention with tamoxifen (Nolvadex®), and sometimes even prophylactic surgery. However, many women with a family history of this disease undergo genetic testing only to find that they do not have BRCA mutations. While this may be comforting in one sense, it does pose an interesting conundrum for screening and prevention in this group because the increased level of risk is unclear.

Researchers in Canada recently evaluated families with a significant history of breast cancer, which they defined as two or more breast cancers among close relatives under the age of 50 or three cases of breast cancer among close relatives at any age. They followed 1,492 women from 365 families for five years. None of the women included in the analysis had BRCA mutations. They then compared the rates of breast cancer with rates found in local breast cancer registries. The results indicated that women with a significant family history of breast cancer had a fourfold increase in breast cancer incidence. The elevation in risk was even higher among women under 40, who had a 15-fold increased risk compared with women under 40 in the general population.

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Based on the results of this study, the researchers concluded that women with a significant family history of breast cancer have a 30 to 40% lifetime risk of developing breast cancer. There was no elevated risk for ovarian, colon, or any other form of cancer. These results provide new insight for screening women with a significant family history of breast cancer, but no BRCA mutation. The researchers observed that women in this population might benefit from intensified screening as well as chemoprevention.


[1] Metcalfe K, Finch A, Poll A, et al. Breast cancer risks in women with a family history of breast or ovarian cancer who have tested negative for a BRCA1 or BRCA2 mutation. Proceedings from American Association for Cancer Research Annual Meeting. Abstract #B7.