Pathogenic variants, family history, and cumulative risk of breast cancer in US women

Inherited pathogenic variants (PVs) in known predispostion genes can greatly increase breast cancer risk, but the combined impact of PV status, family history, and other factors in the general population has not been well described. A pooled analysis of 13 US-based breast cancer case-control studies participating in the CARRIERS consortium, including 67,692 women, found that those with a PV and first-degree family history of breast cancer had an estimated 22.5% risk of breast cancer by age 50 years and a 51.2% risk between 50 and 80 years, compared with an estimated 9.4% risk by age 50 years and 29.7% risk between ages 50 and 80 years in women with a PV but no family history.