BRCA-CRisk: A Contralateral Breast Cancer Risk Prediction Model forBRCACarriers

PURPOSE The absolute cumulative risk of contralateral breast cancer (CBC) for patients with BRCA1/ 2 variants is unknown. The purpose of this study was to develop a CBC risk prediction model for assessing CBC risk for BRCA1/ 2 carriers. METHODS The primary cohort of 491 patients with BRCA1/ 2 variants was derived from a large series of unselected patients with breast cancer. A nomogram was established on the basis of the results of a multivariate Cox regression analysis from this cohort. This model, named BRCA-CRisk, was further validated by an independent cohort of 205 patients with BRCA1/ 2 variants. Discrimination and calibration of the model were assessed. RESULTS In the primary cohort of 491 patients, 66 developed contralateral breast cancer after a median follow-up of 7.0 years. Four variables were significantly associated with risk of CBC and were incorporated in the establishment of the BRCA-CRisk prediction model: younger age at first breast cancer (with continuous variable, P = .002), positive first-degree family history of breast and/or ovarian cancer (hazard ratio [HR], 1.89; 95% CI, 1.16 to 3.08; P = .011), variant located near the 3′ region of BRCA (HR, 2.01; 95% CI, 1.23 to 3.30; P = .006), and endocrine therapy (HR, 0.54; 95% CI, 0.33 to 0.88; P = .013). The area under the time-dependent curves for the 5- and 10-year cumulative risks of CBC were 0.775 and 0.702, respectively. The model was well validated in the independent cohort of 205 BRCA1/ 2 carriers, with area under the curves of 0.750 and 0.691 for 5 and 10 years, respectively. CONCLUSION BRCA-CRisk model provides a useful tool for assessing the absolute cumulative risk of CBC for BRCA1/ 2 carriers and may help carriers and clinicians optimally select risk-reducing strategies on the basis of individual CBC risk.