Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK
Department of Epidemiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
J Med Genet. 2024 Jul 19;61(8):803-809. doi: 10.1136/jmg-2024-109943.
No validation has been conducted for the BOADICEA multifactorial breast cancer risk prediction model specifically in pathogenic variant (PV) carriers to date. Here, we evaluated the performance of BOADICEA in predicting 5-year breast cancer risks in a prospective cohort of PV carriers ascertained through clinical genetic centres.
We evaluated the model calibration and discriminatory ability in the prospective TRANsIBCCS cohort study comprising 1614 and 1365 PV carriers (209 incident cases). Study participants had lifestyle, reproductive, hormonal, anthropometric risk factor information, a polygenic risk score based on 313 SNPs and family history information.
The full multifactorial model considering family history together with all other risk factors was well calibrated overall (E/O=1.07, 95% CI: 0.92 to 1.24) and in quintiles of predicted risk. Discrimination was maximised when all risk factors were considered (Harrell's C-index=0.70, 95% CI: 0.67 to 0.74; area under the curve=0.79, 95% CI: 0.76 to 0.82). The model performance was similar when evaluated separately in or PV carriers. The full model identified 5.8%, 12.9% and 24.0% of PV carriers with 5-year breast cancer risks of <1.65%, <3% and <5%, respectively, risk thresholds commonly used for different management and risk-reduction options.
BOADICEA may be used to aid personalised cancer risk management and decision-making for and PV carriers. It is implemented in the free-access CanRisk tool (https://www.canrisk.org/).
迄今为止，尚未针对携带致病突变（PV）的个体对 BOADICEA 多因素乳腺癌风险预测模型进行验证。在此，我们通过临床遗传中心确定的前瞻性 PV 携带者队列研究，评估了 BOADICEA 预测 5 年乳腺癌风险的性能。
我们评估了前瞻性 TRANsIBCCS 队列研究中模型的校准和区分能力，该研究包括 1614 名和 1365 名 PV 携带者（209 例发病病例）。研究参与者具有生活方式、生殖、激素、人体测量风险因素信息、基于 313 个 SNP 的多基因风险评分和家族史信息。
总体而言，同时考虑家族史和所有其他风险因素的完整多因素模型校准良好（E/O=1.07，95%CI：0.92 至 1.24），且在预测风险的五分位数中也是如此。当考虑所有风险因素时，区分度达到最大值（Harrell's C 指数=0.70，95%CI：0.67 至 0.74；曲线下面积=0.79，95%CI：0.76 至 0.82）。当分别在 或 PV 携带者中进行评估时，该模型的性能相似。完整模型确定了 5.8%、12.9%和 24.0%的 PV 携带者的 5 年乳腺癌风险<1.65%、<3%和<5%，这些风险阈值常用于不同的管理和风险降低选择。
BOADICEA 可用于辅助 和 PV 携带者的个性化癌症风险管理和决策。它被实施在免费的 CanRisk 工具中（https://www.canrisk.org/）。
