Rao Nan-Yan, Hu Zhen, Yu Jin-Ming, Li Wen-Feng, Zhang Bin, Su Feng-Xi, Wu Jiong, Shen Zhen-Zhou, Huang Wei, Shao Zhi-Ming
Department of Oncology, Breast Cancer Institute, Cancer Hospital/Cancer Institute, Shanghai Medical College, Institutes of Biomedical Science, Fudan University, Shanghai 200032, People's Republic of China.
Breast Cancer Res Treat. 2009 Aug;116(3):563-70. doi: 10.1007/s10549-008-0181-4. Epub 2008 Sep 19.
Established models (Penn, Myraid and BRCApro) are useful of estimating the probability that a person has a BRCA mutation. But the value of these models in Chinese population is unclear. The aim of the study is to evaluate the performance of three models on the assisting in pre-test genetic risk counseling.
Three risk assessment models, Penn II, Myriad and BRCApro, were applied to 212 familial breast cancer patients who had undergone BRCA1/2 mutation analysis. Sensitivity, specificity, positive and negative predictive values, likelihood ratios and area under the receiver operator characteristic (ROC) curve were calculated for each model.
Myriad showed a better ROC curve than BRCApro either for BRCA1 or BRCA1/2 combination mutation prediction, but BRCApro had a higher positive likelihood ratio when using 10% as the probability threshold. The performance of three models improved when they were evaluated in 66 patients from high risk families, presenting increased ROC and positive likelihood ratio. Especially that of BRCApro for BRCA2, the ROC was increased to 0.716 and its positive likelihood was 5.6.
Three models had the similar impact on the pre-test probability of BRCA mutation. But at a 10% cutoff point, BRCApro had the best BRCA mutation carrier prediction value. The performance of BRCApro for BRCA2 mutation prediction was improved when it was restricted in patients from high risk families.
已建立的模型（宾夕法尼亚模型、Myriad模型和BRCApro模型）有助于估计一个人携带BRCA突变的概率。但这些模型在中国人群中的价值尚不清楚。本研究的目的是评估这三种模型在辅助检测前遗传风险咨询方面的性能。
将三种风险评估模型，即宾夕法尼亚II模型、Myriad模型和BRCApro模型，应用于212例已进行BRCA1/2突变分析的家族性乳腺癌患者。计算每个模型的灵敏度、特异度、阳性和阴性预测值、似然比以及受试者操作特征（ROC）曲线下面积。
在预测BRCA1或BRCA1/2联合突变时，Myriad模型的ROC曲线比BRCApro模型更好，但当以10%作为概率阈值时，BRCApro模型的阳性似然比更高。在66例来自高危家族的患者中评估这三种模型时，其性能有所提高，ROC和阳性似然比均增加。特别是BRCApro模型对BRCA2的预测，ROC增加到0.716，其阳性似然比为5.6。
三种模型对BRCA突变的检测前概率有相似的影响。但在10%的截断点时，BRCApro模型对BRCA突变携带者的预测价值最佳。当将BRCApro模型限制在高危家族患者中时，其对BRCA2突变预测的性能有所提高。
