Assessing the added value of breast tumor markers in genetic risk prediction model BRCAPRO
Assessing the added value of breast tumor markers in genetic risk prediction model BRCAPRO
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DOI：
10.1007/s10549-012-1958-z
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发表时间：
2012-05-01
影响因子：
3.8
通讯作者：
Arun, Banu
中科院分区：
文献类型：
--
作者：
Biswas, Swati;Tankhiwale, Neelam;Arun, Banu
BRCAPRO模型估计BRCA 1和BRCA 2基因的携带者概率，最近被增强为使用乳腺癌的雌激素受体（ER）和孕激素受体（PR）状态。没有对这些标志的附加值进行独立评估。此外，早期版本的BRCAPRO没有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个生殖细胞测试的个体上训练了增强模型，并在796个个体的单独临床队列上进行了验证，这些个体的测试结果和家族史是可用的。为了建立模型，我们估计了BRCA 1/2突变携带者和非携带者的ER、PR和Her-2/neu状态的联合概率。为了验证，我们获得了有和没有标记的BRCAPRO预测。我们计算了受试者工作特征曲线下面积（AUC）、灵敏度、特异性、预测值和正确的重新分类率。当使用ER和PR时，至少一种突变携带者中预测BRCA 1状态的AUC得到改善。当加入Her-2/neu时，预测任一突变存在的AUC得到改善。在这两种情况下，使用标记也产生了非常显着的正确重新分类改进。乳腺肿瘤标志物可用于预测BRCA 1/2突变状态。ER和PR可以提高BRCA 1和BRCA 2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，特别是ER阳性和Her-2/neu阴性的女性。这些结果支持在临床环境中使用增强版BRCAPRO。
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.