Baretta Zora, Mocellin Simone, Goldin Elena, Olopade Olufunmilayo I, Huo Dezheng
U.O.C. di Oncologia ULSS5 Ovest Vicentino, Ospedale di Montecchio, Montecchio Maggiore (VI) Department of Surgery, Oncology and Gastroenterology, University of Padova Istituto Oncologico Veneto, IOV-IRCCS, Padova, Italy Center for Clinical Cancer Genetics & Global Health, Department of Medicine, University of Chicago, Chicago, IL Department of Public Health Sciences, University of Chicago, Chicago, IL.
Medicine (Baltimore). 2016 Oct;95(40):e4975. doi: 10.1097/MD.0000000000004975.
The contribution of BRCA germline mutational status to breast cancer patients' prognosis is unclear. We aimed to systematically review and perform meta-analysis of the available evidence of effects of BRCA germline mutations on multiple survival outcomes of breast cancer patients as a whole and in specific subgroups of interest, including those with triple negative breast cancer, those with Ashkenazi Jewish ancestry, and patients with stage I-III disease.
Sixty studies met all inclusion criteria and were considered for this meta-analysis. These studies involved 105,220 breast cancer patients, whose 3588 (3.4%) were BRCA mutations carriers. The associations between BRCA genes mutational status and overall survival (OS), breast cancer-specific survival (BCSS), recurrence-free survival (RFS), and distant metastasis-free survival (DMFS) were evaluated using random-effect models.
BRCA1 mutation carriers have worse OS than BRCA-negative/sporadic cases (hazard ratio, HR 1.30, 95% CI: 1.11-1.52) and worse BCSS than sporadic/BRCA-negative cases among patients with stage I-III breast cancer (HR 1.45, 95% CI: 1.01-2.07). BRCA2 mutation carriers have worse BCSS than sporadic/BRCA-negative cases (HR 1.29, 95% CI: 1.03-1.62), although they have similar OS. Among triple negative breast cancer, BRCA1/2 mutations carriers had better OS than BRCA-negative counterpart (HR 0.49, 95% CI: 0.26-0.92). Among Ashkenazi Jewish women, BRCA1/2 mutations carriers presented higher risk of death from breast cancer (HR 1.44, 95% CI: 1.05-1.97) and of distant metastases (HR 1.82, 95% CI: 1.05-3.16) than sporadic/BRCA-negative patients.
Our results support the evaluation of BRCA mutational status in patients with high risk of harboring BRCA germline mutations to better define the prognosis of breast cancer in these patients.
BRCA种系突变状态对乳腺癌患者预后的影响尚不清楚。我们旨在系统评价并对BRCA种系突变对乳腺癌患者整体及特定感兴趣亚组（包括三阴性乳腺癌患者、阿什肯纳兹犹太裔患者以及I-III期疾病患者）多种生存结局影响的现有证据进行荟萃分析。
60项研究符合所有纳入标准并被纳入该荟萃分析。这些研究涉及105220例乳腺癌患者，其中3588例（3.4%）为BRCA突变携带者。使用随机效应模型评估BRCA基因突变状态与总生存期（OS）、乳腺癌特异性生存期（BCSS）、无复发生存期（RFS）和无远处转移生存期（DMFS）之间的关联。
在I-III期乳腺癌患者中，BRCA1突变携带者的总生存期比BRCA阴性/散发性病例差（风险比，HR 1.30，95%可信区间：1.11-1.52），乳腺癌特异性生存期比散发性/BRCA阴性病例差（HR 1.45，95%可信区间：1.01-2.07）。BRCA2突变携带者的乳腺癌特异性生存期比散发性/BRCA阴性病例差（HR 1.29，95%可信区间：1.03-1.62），尽管他们的总生存期相似。在三阴性乳腺癌中，BRCA1/2突变携带者的总生存期比BRCA阴性者好（HR 0.49，95%可信区间：0.26-0.92）。在阿什肯纳兹犹太女性中，BRCA1/2突变携带者死于乳腺癌的风险（HR 1.44，95%可信区间：1.05-1.97）和远处转移的风险（HR 1.82，95%可信区间：1.05-3.16）高于散发性/BRCA阴性患者。
我们的结果支持对具有BRCA种系突变高风险的患者评估BRCA突变状态，以更好地明确这些患者的乳腺癌预后。
