Menes Tehillah S, Terry Mary Beth, Goldgar David, Andrulis Irene L, Knight Julia A, John Esther M, Liao Yuyan, Southey Melissa, Miron Alexander, Chung Wendy, Buys Saundra S
Department of Surgery, Tel Aviv Sourasky Medical Center, 6 Weizman St, Tel Aviv, Israel,
Breast Cancer Res Treat. 2015 Jun;151(3):653-60. doi: 10.1007/s10549-015-3419-y. Epub 2015 May 15.
BReast CAncer genes 1 and 2 (BRCA1 and BRCA2) mutation carriers diagnosed with breast cancer are at increased risk of developing a second primary breast cancer. Data from high-risk clinics may be subject to different biases which can cause both over and underestimation of this risk. Using data from a large multi-institutional family registry we estimated the 10-year cumulative risk of second primary breast cancer including more complete testing information on family members. We prospectively followed 800 women diagnosed with breast cancer from the Breast Cancer Family Registry (BCFR) who were carriers of a BRCA1 or BRCA2 pathogenic mutation or a variant of unknown clinical significance. In order to limit survival and ascertainment bias, cases were limited to those diagnosed with a first primary breast cancer from 1994 to 2001 and enrolled in the BCFR within 3 years after their cancer diagnosis. We excluded women enrolled after being diagnosed with a second breast cancer. We calculated 10-year incidence of second primary breast cancers. The 10-year incidence of a second primary breast cancer was highest in BRCA1 mutation carriers (17 %; 95 % CI 11-25 %), with even higher estimates in those first diagnosed under the age of 40 (21 %; 95 % CI 13-34 %). Lower rates were found in BRCA2 mutation carriers (7 %; 95 % CI 3-15 %) and women with a variant of unknown clinical significance (6 %; 95 % CI 4-9 %). Whereas the cumulative 10-year incidence of second primary breast cancer is high in BRCA1 mutation carriers, the estimates in BRCA2 mutation carriers and women with variants of unknown clinical significance are similar to those reported in women with sporadic breast cancer.
被诊断患有乳腺癌的乳腺癌1号和2号基因（BRCA1和BRCA2）突变携带者发生第二原发性乳腺癌的风险增加。来自高风险诊所的数据可能存在不同的偏差，这可能导致对该风险的高估和低估。我们使用来自一个大型多机构家庭登记处的数据，估计了第二原发性乳腺癌的10年累积风险，其中包括关于家庭成员更完整的检测信息。我们前瞻性地跟踪了乳腺癌家庭登记处（BCFR）中800名被诊断患有乳腺癌的女性，她们是BRCA1或BRCA2致病突变或临床意义不明的变异的携带者。为了限制生存和确定偏差，病例仅限于那些在1994年至2001年被诊断患有第一原发性乳腺癌且在癌症诊断后3年内加入BCFR的患者。我们排除了在被诊断患有第二乳腺癌后入组的女性。我们计算了第二原发性乳腺癌的10年发病率。BRCA1突变携带者中第二原发性乳腺癌的10年发病率最高（17%；95%可信区间11 - 25%），在那些首次诊断年龄在40岁以下的携带者中估计值甚至更高（21%；95%可信区间13 - 34%）。在BRCA2突变携带者（7%；95%可信区间3 - 15%）和临床意义不明的变异女性（6%；95%可信区间4 - 9%）中发现的发病率较低。虽然BRCA1突变携带者中第二原发性乳腺癌的累积10年发病率很高，但BRCA2突变携带者和临床意义不明的变异女性的估计值与散发性乳腺癌女性中报告的估计值相似。
