Recent BRCAPRO upgrades significantly improve calibration

Abstract

The recent release of version 2.0-8 of the BayesMendel package contains an updated BRCAPRO risk prediction model, which includes revised modeling of contralateral breast cancer (CBC) penetrance, provisions for pedigrees of mixed ethnicity and an adjustment for mastectomies among family members. We estimated penetrance functions for CBC by a combination of parametric survival modeling of literature data and deconvolution of SEER9 data. We then validated the resulting updated model of CBC in BRCAPRO by comparing it with the previous release (BayesMendel 2.0-7), using pedigrees from the Cancer Genetics Network (CGN) Model Validation Study. Version 2.0-8 of BRCAPRO discriminates BRCA1/BRCA2 carriers from noncarriers with similar accuracy compared with the previous version (increase in AUC, 0.0043), is slightly more precise in terms of the root-mean-square error (decrease in RMSE, 0.0108), and it significantly improves calibration (ratio of observed to expected events of 0.9765 in version 2.0-8, compared with 0.8910 in version 2.0-7). We recommend that the new version be used in clinical counseling, particularly in settings where families with CBC are common. © 2014 American Association for Cancer Research.