The Impact of Breast Cancer Polygenic Risk Score Disclosure on Decisional Conflict Around Risk-Reducing Mastectomy in BRCA1/2 Carriers

Abstract

PurposeFemale BRCA1/2 carriers face high breast cancer risks and complex preventive decisions, which can generate decisional conflict. Polygenic Risk Scores (PRS) offer individualized risk estimates that may support decision-making. We examine whether PRS disclosure reduces decisional conflict in BRCA1/2 carriers and whether PRS magnitude interacts with numeracy and tolerance for ambiguity. MethodsUnaffected BRCA1/2 carriers (N=354) were assessed pre PRS disclosure (T0), one-week (T1), and six-months post-disclosure (T2). PRS were translated into 10-year and lifetime absolute breast cancer risk estimates. Mixed-effects models tested changes in decisional conflict, and regression/moderation analyses tested PRS effects and interactions with numeracy and tolerance for ambiguity. ResultsDecisional conflict decreased significantly after PRS disclosure. Higher 10-year risk was associated with greater decisional conflict immediately after disclosure. Lifetime risk alone did not predict conflict. Tolerance for ambiguity moderated the effect of lifetime risk at T1: women with low/average tolerance experienced higher conflict with high PRS and lower conflict with low PRS. Numeracy, age, and family cancer history did not moderate PRS effects. ConclusionDecisional conflict decreased post-PRS disclosure, with short-term responses influenced by tolerance for ambiguity. Findings suggest that PRS can complement standard BRCA1/2 genetic counseling and highlight the need for tailored risk communication.