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Apart from pathologic diagnoses of atypical hyperplasia, few factors aid in breast cancer risk assessment of these patients. We assessed whether a 313\u2013single nucleotide variation (formerly single-nucleotide polymorphism) polygenic risk score stratifies risk of benign breast disease patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We pooled data from 5 Breast Cancer Association Consortium case-control studies (mean age\u2009=\u200959.9\u2009years), including 6706 participants with breast cancer and 8488 participants without breast cancer. Using logistic regression, we estimated breast cancer risk associations by self-reported benign breast disease history and strata of polygenic risk score, with median polygenic risk score category among women without benign breast disease as the referent. We assessed interactions and mediation of benign breast disease and polygenic risk score with breast cancer risk.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Benign breast disease history was associated with increased breast cancer risk (odds ratio [OR]\u2009=\u20091.48, 95% confidence interval [CI] = 1.37 to 1.60; P\u2009&amp;lt;\u2009.001). Polygenic risk score increased breast cancer risk, irrespective of benign breast disease history (Pinteraction\u2009=\u2009.48), with minimal evidence of mediation of either factor by the other. Women with benign breast disease and polygenic risk score in the highest tertile had more than twofold increased odds of breast cancer (OR\u2009=\u20092.73, 95% CI = 2.41 to 3.09), and those with benign breast disease and polygenic risk score in the lowest tertile experienced reduced breast cancer risk (OR\u2009=\u20090.79, 95% CI = 0.70 to 0.91) compared with the referent group. Women with benign breast disease and polygenic risk score in the highest decile had a 3.7-fold increase (95% CI = 3.00 to 4.61) compared with those with median polygenic risk score without benign breast disease.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Breast cancer risks are elevated among women with benign breast disease and increase progressively with polygenic risk score, suggesting that optimal combinations of these factors may improve risk stratification.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jnci\/djae255","type":"journal-article","created":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T14:40:08Z","timestamp":1729089608000},"page":"456-464","source":"Crossref","is-referenced-by-count":7,"title":["Polygenic risk scores stratify breast cancer risk among women with benign breast disease"],"prefix":"10.1093","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9222-8808","authenticated-orcid":false,"given":"Mark E","family":"Sherman","sequence":"first","affiliation":[{"name":"Department of Quantitative Health Sciences, Mayo Clinic , Jacksonville, FL 32224,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8492-9102","authenticated-orcid":false,"given":"Stacey J","family":"Winham","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences, Mayo Clinic , Rocheseter, MN 55905,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6242-5221","authenticated-orcid":false,"given":"Robert A","family":"Vierkant","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences, Mayo Clinic , Rocheseter, MN 55905,","place":["United 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