PURPOSE Breast cancer (BC) risk prediction allows systematic identification of individuals at highest and lowest risk. We extend the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) risk model to incorporate the effects of polygenic risk scores (PRS) and other risk factors (RFs). METHODS BOADICEA incorporates the effects of truncating variants in BRCA1, BRCA2, PALB2, CHEK2, and ATM; a PRS based on 313 single-nucleotide polymorphisms (SNPs) explaining 20% of BC polygenic variance; a residual polygenic component accounting for other genetic/familial effects; known lifestyle/hormonal/reproductive RFs; and mammographic density, while allowing for missing information. RESULTS Among all factors considered, the predicted UK BC risk distribution is widest for the PRS, followed by mammographic density. The highest BC risk stratification is achieved when all genetic and lifestyle/hormonal/reproductive/anthropomorphic factors are considered jointly. With all factors, the predicted lifetime risks for women in the UK population vary from 2.8% for the 1st percentile to 30.6% for the 99th percentile, with 14.7% of women predicted to have a lifetime risk of ≥17-<30% (moderate risk according to National Institute for Health and Care Excellence [NICE] guidelines) and 1.1% a lifetime risk of ≥30% (high risk). CONCLUSION This comprehensive model should enable high levels of BC risk stratification in the general population and women with family history, and facilitate individualized, informed decision-making on prevention therapies and screening.

中文翻译：

---

BOADICEA：结合遗传和非遗传风险因素的综合乳腺癌风险预测模型。

目的 乳腺癌 (BC) 风险预测可以系统地识别风险最高和最低的个体。我们扩展了乳腺癌和卵巢疾病发病率分析和携带者估计算法 (BOADICEA) 风险模型，以纳入多基因风险评分 (PRS) 和其他风险因素 (RF) 的影响。方法 BOADICEA 结合了 BRCA1、BRCA2、PALB2、CHEK2 和 ATM 中截短变体的影响；基于 313 个单核苷酸多态性 (SNP) 的 PRS，解释了 20% 的 BC 多基因变异；剩余的多基因成分解释了其他遗传/家族效应；已知的生活方式/荷尔蒙/生殖 RF；和乳房X光密度，同时允许丢失信息。结果 在考虑的所有因素中，PRS 的预测英国 BC 风险分布最宽，其次是乳房 X 光密度。当综合考虑所有遗传和生活方式/激素/生殖/拟人化因素时，可实现最高的 BC 风险分层。考虑到所有因素，英国人口中女性的预测终生风险从第 1 个百分位数的 2.8% 到第 99 个百分位数的 30.6% 不等，其中 14.7% 的女性预计终生风险≥17-<30%（中等）根据国家健康与护理卓越研究所 [NICE] 指南，风险为 1.1%；终生风险≥30%（高风险）。结论 这一综合模型应该能够对普通人群和有家族史的女性进行高水平的 BC 风险分层，并促进在预防治疗和筛查方面做出个性化、知情的决策。