{"doi":"10.1101/2025.11.10.25339918","title":"The Impact of Breast Cancer Polygenic Risk Score Disclosure on Decisional Conflict Around Risk-Reducing Mastectomy in <i>BRCA1/2</i> Carriers","abstract":"Abstract Purpose Female 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. Methods Unaffected 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. Results Decisional 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. Conclusion Decisional 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.","journal":"medRxiv","year":2025,"id":559500,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9556,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1135820,"name":"C.M. 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Stadler","orcid":"0000-0002-6985-2864","position":15,"is_corresponding":false},{"id":108795,"name":"Kenneth Offit","orcid":"0000-0002-2180-2032","position":16,"is_corresponding":false},{"id":95411,"name":"Judy E. Garber","orcid":"0000-0001-9449-3982","position":17,"is_corresponding":false},{"id":78635,"name":"Susan M. Domchek","orcid":"0000-0002-5914-7272","position":18,"is_corresponding":false},{"id":90758,"name":"Mark E. Robson","orcid":"0000-0002-3109-1692","position":19,"is_corresponding":false},{"id":868848,"name":"Jada G. 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