Contralateral risk-reducing local therapy in breast cancer patients with BRCA1/2 mutations: systemic review and meta-analysis
Ziqi Jia, Jiaxin Li, Yuelun Zhang, Xin Wang, Jiahua Xing, Zeyu Xing, Xin Huang, Gang Liu, Menglu Zhang, Kexin Feng, Jiang Wu, Wenyan Wang, Jie Wang, Jiaqi Liu, Xiang Wang
Abstract
Abstract Background Unilateral breast cancer (UBC) patients with germline pathogenic BRCA1/2 variants have a higher risk of developing contralateral breast cancer (CBC) and need contralateral risk-reducing local treatments, including contralateral risk-reducing mastectomy (CRRM) and prophylactic irradiation (CPI). The aim of our study was to systematically explore the efficacy of CRRM and CPI in reducing CBC risk and increasing survival. Methods A search was done, and eligible randomized trials and cohort studies should include and compare UBC patients with germline pathogenic BRCA1/2 variants who have and have not received contralateral risk-reducing local treatment. Random-effects meta-analysis was used in this study. Primary outcomes of the studies included overall survival (OS) and the incidence of contralateral breast cancer (CBC), and secondary outcomes included breast cancer-specific survival (BCSS). Results A total of five studies with 1769 UBC patients with germline pathogenic BRCA1/2 variants were enrolled in our meta-analysis. CRRM was correlated with a lower risk of CBC in UBC patients with germline pathogenic BRCA1/2 variants (summary RR = 0.07; 95%CI 0.03–0.13, I 2 = 3%), a significantly increased OS (summary RR, 1.15; 95%CI 1.04–1.26, I 2 = 26%) and a significantly increased BCSS (summary RR, 1.18; 95%CI 1.07–1.31, I 2 = 64%) compared with surveillance. CPI also decreased the risk of CBC (RR 0.02; 95%CI 0.05–0.88) but did not significantly improve OS (RR 0.97; 95%CI 0.90–1.05) and BCSS (RR 0.97; 95%CI 0.90–1.05) compared with surveillance. Conclusions CRRM reduces CBC risk and increases OS and BCSS in UBC patients with germline pathogenic BRCA1/2 variants, and could be offered as a risk-reducing local treatment. For those who oppose CRRM, CPI could be offered for CBC-risk reduction, while its survival benefit is still uncertain.