Department of Biostatistics, School of Public Health, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX 76107-2699, USA.
Breast Cancer Res Treat. 2012 May;133(1):347-55. doi: 10.1007/s10549-012-1958-z. Epub 2012 Jan 21.
The BRCAPRO model estimates carrier probabilities for the BRCA1 and BRCA2 genes, and was recently enhanced to use estrogen receptor (ER) and progesterone receptor (PR) status of breast cancer. No independent assessment of the added value of these markers exists. Moreover, earlier versions of BRCAPRO did not use human epidermal growth factor receptor 2 (Her-2/neu) status of breast cancer. Here, we incorporate Her-2/neu in BRCAPRO and validate all the markers. We trained the enhanced model on 406 germline tested individuals, and validated on a separate clinical cohort of 796 individuals for whom test results and family history are available. For model-building, we estimated joint probabilities of ER, PR, and Her-2/neu status for carriers and non-carriers of BRCA1/2 mutations. For validation, we obtained BRCAPRO predictions with and without markers. We calculated area under the receiver operating characteristic curve (AUC), sensitivity, specificity, predictive values, and correct reclassification rates. The AUC for predicting BRCA1 status among individuals who are carriers of at least one mutation improved when ER and PR were used. The AUC for predicting the presence of either mutation improved when Her-2/neu was added. Use of markers also produced highly significant correct reclassification improvements in both cases. Breast tumor markers are useful for prediction of BRCA1/2 mutation status. ER and PR improve discrimination between BRCA1 and BRCA2 mutation carriers while Her-2/neu helps discriminate between carriers and non-carriers, particularly among women who are ER positive and Her-2/neu negative. These results support the use of the enhanced version of BRCAPRO in clinical settings.
BRCAPRO 模型估计 BRCA1 和 BRCA2 基因的携带者概率，最近已增强为使用乳腺癌的雌激素受体 (ER) 和孕激素受体 (PR) 状态。目前尚不存在对这些标志物附加价值的独立评估。此外，BRCAPRO 的早期版本并未使用乳腺癌的人表皮生长因子受体 2 (Her-2/neu) 状态。在这里，我们将 Her-2/neu 纳入 BRCAPRO 并验证所有标志物。我们在 406 个经过种系测试的个体上训练增强模型，并在另外 796 个具有测试结果和家族史的临床队列上进行验证。对于模型构建，我们估计了 ER、PR 和 Her-2/neu 状态在 BRCA1/2 突变携带者和非携带者中的联合概率。对于验证，我们获得了有标记和无标记的 BRCAPRO 预测。我们计算了接收器工作特征曲线 (AUC) 的面积、敏感性、特异性、预测值和正确重新分类率。当使用 ER 和 PR 时，预测至少携带一种突变的个体中 BRCA1 状态的 AUC 得到改善。当添加 Her-2/neu 时，预测存在任何一种突变的 AUC 得到改善。在这两种情况下，使用标志物还可产生高度显著的正确重新分类改善。乳腺肿瘤标志物可用于预测 BRCA1/2 突变状态。ER 和 PR 改善了 BRCA1 和 BRCA2 突变携带者之间的区分，而 Her-2/neu 有助于区分携带者和非携带者，尤其是在 ER 阳性和 Her-2/neu 阴性的女性中。这些结果支持在临床环境中使用增强版的 BRCAPRO。
