{"doi":"10.3390/cancers13143533","title":"Genomic Risk Prediction for Breast Cancer in Older Women","abstract":"Genomic risk prediction models for breast cancer (BC) have been predominantly developed with data from women aged 40–69 years. Prospective studies of older women aged ≥70 years have been limited. We assessed the effect of a 313-variant polygenic risk score (PRS) for BC in 6339 older women aged ≥70 years (mean age 75 years) enrolled into the ASPREE trial, a randomized double-blind placebo-controlled clinical trial investigating the effect of daily 100 mg aspirin on disability-free survival. We evaluated incident BC diagnoses over a median follow-up time of 4.7 years. A multivariable Cox regression model including conventional BC risk factors was applied to prospective data, and re-evaluated after adding the PRS. We also assessed the association of rare pathogenic variants (PVs) in BC susceptibility genes (BRCA1/BRCA2/PALB2/CHEK2/ATM). The PRS, as a continuous variable, was an independent predictor of incident BC (hazard ratio (HR) per standard deviation (SD) = 1.4, 95% confidence interval (CI) 1.3–1.6) and hormone receptor (ER/PR)-positive disease (HR = 1.5 (CI 1.2–1.9)). Women in the top quintile of the PRS distribution had over two-fold higher risk of BC than women in the lowest quintile (HR = 2.2 (CI 1.2–3.9)). The concordance index of the model without the PRS was 0.62 (95% CI 0.56–0.68), which improved after addition of the PRS to 0.65 (95% CI 0.59–0.71). Among 41 (0.6%) carriers of PVs in BC susceptibility genes, we observed no incident BC diagnoses. Our study demonstrates that a PRS predicts incident BC risk in women aged 70 years and older, suggesting potential clinical utility extends to this older age group.","journal":"Cancers","year":2021,"id":198498,"datarank":0.3596842909197557,"base_score":2.3978952727983707,"endowment":2.3978952727983707,"self_citation_contribution":0.3596842909197557,"citation_network_contribution":0.0,"self_endowment_contribution":0.3596842909197557,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.954,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":374280,"name":"Andrew Bakshi","orcid":"0000-0001-5650-7036","position":1,"is_corresponding":false},{"id":301798,"name":"Moeen Riaz","orcid":"0000-0001-5858-3788","position":2,"is_corresponding":false},{"id":351162,"name":"Suzanne G. 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