The impact of breast cancer polygenic risk score disclosure on decisional conflict around risk-reducing mastectomy in women with pathogenic BRCA1/2 variants.

Women with BRCA1/2 pathogenic variants (PVs) face high breast cancer risks and complex preventive decisions, including whether to undergo risk-reducing mastectomy, which can generate decisional conflict. Polygenic risk scores (PRSs) offer individualized risk estimates that may support informed preventive decisions. We examined whether PRS disclosure reduces decisional conflict about risk-reducing mastectomy in women with BRCA1/2 PVs and whether PRS magnitude interacts with individual characteristics. Unaffected women with BRCA1/2 PVs (N = 354) were assessed before PRS disclosure (T0), 1 week (T1), and 6 months post-disclosure (T2). PRSs were translated into 10-year and lifetime absolute breast cancer risk estimates. Mixed-effects models were used to test changes in decisional conflict and generalized regression analyses to test PRS effects and interactions with individual characteristics. Decisional conflict decreased significantly after PRS disclosure. A 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 lower or medium tolerance experienced higher conflict with high PRSs and lower conflict with low PRSs. Numeracy, age, and family cancer history did not moderate PRS effects. Decisional conflict decreased post-PRS disclosure, with short-term responses varying by tolerance for ambiguity, highlighting the importance of tailoring risk communication to patients' psychological characteristics.