Background: The utility of incorporating detailed family history into breast cancer risk prediction hinges on its independent contribution to breast cancer risk. We evaluated associations between detailed family history and breast cancer risk while accounting for breast density. Methods: We followed 222,019 participants aged 35-74 in the Breast Cancer Surveillance Consortium, of whom 2,456 developed invasive breast cancer. We calculated standardized breast cancer risks within joint strata of breast density and simple (1st-degree female relative) or detailed (1st-degree, 2nd-degree, or 1st- and 2nd-degree female relative) breast cancer family history. We fit log-binomial models to estimate age-specific breast cancer associations for simple and detailed family history, accounting for breast density. Results: Simple 1st-degree family history was associated with increased breast cancer risk compared with no 1st-degree history (RR=1.5, 95%CI 1.0-2.1 at age 40; RR=1.5, 95%CI 1.3-1.7 at age 50; RR=1.4, 95%CI 1.2-1.6 at age 60; RR=1.3, 95%CI 1.1-1.5 at age 70). Breast cancer associations with detailed family history were strongest for women with 1st- and 2nd-degree family history compared with no history (RR=1.9, 95%CI 1.1-3.2 at age 40); this association weakened in higher age groups (RR=1.2, 95%CI 0.88-1.5 at age 70). Associations did not change substantially when adjusted for breast density. Conclusion: Even with adjustment for breast density, a history of breast cancer in both 1st- and 2nd-degree relatives is more strongly associated with breast cancer than simple 1st-degree family history. Impact: Future efforts to improve breast cancer risk prediction models should evaluate detailed family history as a risk factor.
- Received October 10, 2016.
- Revision received December 19, 2016.
- Accepted January 5, 2017.
- Copyright ©2017, American Association for Cancer Research.