Breast Cancer Risk Modification in Women with Pathogenic Variants in BRCA1, BRCA2, ATM, CHEK2, and PALB2

Area of Science:

• Oncology
• Genetics
• Epidemiology

Background:

• Pathogenic variants (PVs) are known genetic factors influencing cancer risk.
• Established breast cancer risk factors are well-documented.
• The interplay between PVs and traditional risk factors requires further investigation.

Purpose of the Study:

• To determine if established breast cancer risk factors modify risk in individuals with pathogenic variants (PVs).
• To investigate the association between specific risk factors and breast cancer incidence in PV carriers within the Women's Health Initiative (WHI) cohort.

Main Methods:

• Analysis of data from the Women's Health Initiative (WHI) study.
• Comparison of breast cancer risk between PV carriers and non-carriers across various established risk factors.
• Stratification of risk by specific gene variants (e.g., ATM, CHEK2) and menopausal hormone therapy (MHT) use.

Main Results:

• Most established risk factors did not confer a substantial (≥2-fold) increase in breast cancer risk among PV carriers.
• A potential interaction was observed between MHT use and carrying ATM or CHEK2 PVs, suggesting a possible increased risk.

Conclusions:

• Established risk factors generally do not significantly elevate breast cancer risk in PV carriers.
• Menopausal hormone therapy may warrant cautious consideration for individuals carrying ATM or CHEK2 pathogenic variants.
• Findings can inform genetic counseling and future research on MHT and breast cancer risk.