Highlight
– Pathogenic variants (PVs) in genes such as BRCA1, BRCA2, PALB2, ATM, and CHEK2 significantly increase breast cancer risk.
– Family history modulates the risk conferred by PVs, especially for BRCA1 and PALB2.
– Cumulative breast cancer risk by age 80 years varies widely, reaching over 70% for PALB2 PV carriers with a family history.
– Risk estimates differ across racial and ethnic groups, and by modifiable epidemiologic factors, underscoring the need for individualized assessment.

