乳腺癌易感基因突变与患者生存结局
乳腺癌易感基因BRCA1和BRCA2是重要的抑癌基因，如果发生致病突变，容易引起乳腺癌等恶性肿瘤。不过，关于BRCA突变对乳腺癌患者生存结局的影响，既往研究结果不一致。
2021年2月9日，施普林格自然旗下《乳腺癌研究与治疗》在线发表北京大学人民医院刘淼、谢菲、刘苗雨、王殊等学者的系统回顾和荟萃分析，总结了BRCA突变对乳腺癌患者生存结局的影响。
作者通过PubMed、EMBASE、Cochrane对BRCA突变与BRCA正常乳腺癌患者生存结局比较研究进行了系统检索。研究结局为总生存、无病生存、无远处转移生存、乳腺癌相关生存，根据风险比及其95%置信区间进行定量分析，根据三阴性乳腺癌和随访时间进行亚组生存分析，根据PRISMA指南进行荟萃分析。
结果，30篇研究报告共计3万5972例患者（平均年龄45.6岁）被纳入分析。
BRCA1突变与未突变的患者相比：
总死亡风险高20%（风险比：1.2，95%置信区间：1.08～1.33，P=0.0008）
复发或死亡风险相似
乳腺癌相关死亡风险相似
远处转移或死亡风险相似
BRCA2突变与未突变的患者相比：
总死亡风险相似
复发或死亡风险高35%（风险比：1.35，95%置信区间：1.1～1.67，P=0.0049）。
乳腺癌相关死亡风险高46%（风险比：1.46，95%置信区间：1.26～1.7，P<0.0001）
远处转移或死亡风险相似
BRCA1突变与未突变的三阴性乳腺癌患者相比：
总死亡风险相似
复发或死亡风险高65%（风险比：1.65，95%置信区间：1.08～2.54，P=0.0216）
乳腺癌相关死亡风险相似
远处转移或死亡风险相似
根据随访时间，BRCA1突变与未突变的患者相比：
随访≤5年：总死亡风险高48%（风险比：1.48）
随访>5年：总死亡风险高14%（风险比：1.14）
根据随访时间，BRCA2突变与未突变的患者相比：
随访≤5年：总死亡风险相似
随访>5年：总死亡风险高39%（风险比：1.39，P<0.05）
因此，该研究结果表明，BRCA1或BRCA2突变的乳腺癌患者生存结局较差，故对乳腺癌患者进行BRCA突变筛查，可能有助于制定治疗策略并改善其生存结局。
Breast Cancer Res Treat. 2021 Feb 9. Online ahead of print.
Association between BRCA mutational status and survival in patients with breast cancer: a systematic review and meta-analysis.
Miao Liu, Fei Xie, Miaoyu Liu, Yi Zhang, Shu Wang.
Peking University, People's Hospital, Beijing, China.
BACKGROUND: Studies evaluating role of BRCA mutations on the survival outcomes in breast cancer (BC) patients have given confounding results and hence, in this meta-analysis, we assessed the impact of BRCA mutations on survival in BC patients.
METHODS: Studies comparing survival outcomes of BC patients having BRCA mutations against wildtype BRCA phenotype were retrieved from PubMed, EMBASE, and Cochrane Library. Overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and breast cancer-specific survival (BCCS) were the outcomes. Hazard ratio (HR) with 95% confidence interval (CI) was used for analysis. Subgroup analysis was performed for survival based on triple negative breast cancer (TNBC) and follow-up durations. The meta-analysis was performed as per PRISMA guidelines.
RESULTS: Altogether, 30 articles with 35,972 patients (mean age 45.6 years) were included. Patients with BRCA 1 mutation had significantly lower OS (HR [95% CI] 1.2 [1.08, 1.33]; P<0.001), BRCA 2 mutation had significantly lower DFS (HR [95% CI] 1.35 [1.1, 1.67]; P=0.0049) and BCSS (HR [95%CI] 1.46 [1.26, 1.7]; P<0.0001), and TNBC patients with BRCA 1 mutation had significantly poor DFS (HR [95% CI] 1.65 [1.08, 2.54]; P=0.0216). Based on follow-up duration, the OS in BRCA 1-mutated patients revealed significantly poorer outcomes in studies with≤5 years (HR 1.48) and>5 years (HR 1.14) of follow-up. In BRCA 2 -mutated patients, the OS was significantly poorer in studies with>5 years of follow-up (HR 1.39, P<0.05).
CONCLUSION: BC patients with BRCA 1 or BRCA 2 mutations had poor survival outcomes and hence screening patients with BC for BRCA mutations might help in strategizing their treatment and improving their survival.
KEYWORDS: BRCA; Breast cancer; Survival; Prognosis
DOI: 10.1007/s10549-021-06104-y
