Purpose Most breast biopsies are diagnosed as benign breast disease (BBD), with 1.5- to fourfold increased breast cancer (BC) risk. Apart from pathologic diagnoses of atypical hyperplasia, few factors aid in BC risk assessment of these patients. We assessed whether a 313-SNP polygenic risk score (PRS) stratifies risk of BBD patients. Patients and Methods We pooled data from five Breast Cancer Association Consortium case-control studies (mean age = 59.9 years), including 6,706 cases and 8,488 controls. Using logistic regression, we estimated BC risk associations by self-reported BBD history and strata of PRS, with median PRS category among women without BBD as the referent. We assessed interactions and mediation of BBD and PRS with BC risk. Results BBD history was associated with increased BC risk (OR = 1.48, 95% CI: 1.37-1.60; p < .001). PRS increased BC risk, irrespective of BBD history (p-interaction = 0.48), with minimal evidence of mediation of either factor by the other. Women with BBD and PRS in the highest tertile had over 2-fold increased odds of BC (OR = 2.73, 95% CI: 2.41-3.09) and those with BBD and PRS in the lowest tertile experienced reduced BC risk (OR = 0.79, 95% CI: 0.70-0.91), compared to the reference group. Women with BBD and PRS in the highest decile had a 3.7- fold increase (95% CI: 3.00-4.61) compared to those with median PRS without BBD. Conclusion BC risks are elevated among women with BBD and increase progressively with PRS, suggesting that optimal combinations of these factors may improve risk stratification.

中文翻译：

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多基因风险评分对良性乳腺疾病女性的乳腺癌风险进行分层


目的 大多数乳腺活检被诊断为良性乳腺疾病 （BBD），乳腺癌 （BC） 风险增加 1.5 至 4 倍。除了非典型增生的病理诊断外，很少有因素有助于这些患者的 BC 风险评估。我们评估了 313-SNP 多基因风险评分 （PRS） 是否对 BBD 患者的风险进行分层。患者和方法 我们汇总了来自五项乳腺癌协会联盟病例对照研究 （平均年龄 = 59.9 岁） 的数据，包括 6,706 例病例和 8,488 例对照。使用 logistic 回归，我们通过自我报告的 BBD 病史和 PRS 的分层来估计 BC 风险关联，以无 BBD 的女性的中位 PRS 类别作为参考。我们评估了 BBD 和 PRS 与 BC 风险的相互作用和中介作用。结果 BBD 病史与 BC 风险增加相关 （OR = 1.48,95% CI：1.37-1.60;p < .001）。PRS 增加了 BC 风险，与 BBD 病史无关 （p-交互作用 = 0.48），而任何一个因素被另一个因素介导的证据最少。与参考组相比，BBD 和 PRS 在最高三分位数的女性患 BC 几率增加了 2 倍以上 （OR = 2.73,95% CI： 2.41-3.09），而 BBD 和 PRS 在最低三分位数的 BC 风险降低 （OR = 0.79,95% CI： 0.70-0.91）。与无 BBD 的中位 PRS 女性相比，BBD 和 PRS 在最高十分位数的女性增加了 3.7 倍 （95% CI： 3.00-4.61）。结论 BBD 女性的 BC 风险升高，而 PRS 的 BC 风险逐渐增加，表明这些因素的最佳组合可能会改善风险分层。