A systematic review and meta-analysis of BRCA1/2 mutation for predicting the effect of platinum-based chemotherapy in triple-negative breast cancer

Abstract

Introduction: Platinum-based chemotherapy (PBC) remains the mainstay of treatments for triple-negative breast cancer (TNBC). TNBC is a heterogeneous group, the issue of whether BRCA1/2 mutation carriers have a particular sensitivity to platinum agents is inconclusive. We conducted a meta-analysis to explore the relationship between BRCA1/2 mutation and PBC susceptibility in individuals with TNBC, aiming to gain more information on the size of the benefit of PBC in BRCA1/2 mutation carriers.

Materials and methods: All studies applying PBC with a subgroup of BRCA1/2 status were included. All endpoints, including pCR and RCB in the neoadjuvant phase, DFS in the adjuvant phase, ORR, PFS, and OS in the advanced phase, were assessed using HRs and 95% Cl.

Results: From the 22 studies included, there were 2158 patients with TNBC, with 392 (18%) bearing the BRCA1/2 gene mutation. Based on 13 studies applying neoadjuvant PBC, we discovered that BRCA1/2 mutation was substantially associated with a 17.6% increased pCR rate (HR 1.32, 95% CI 1.17-1.49, p < 0.00001; I² = 51%). Same result was observed in RCB0/I index (HR 1.38, 95% CI 1.08-1.76, P = 0.009; I² = 0%). The meta-analysis of 6 trials addressing advanced therapy revealed that ORR rates were significantly higher in patients with BRCA1/2 mutation (HR 1.91, 95% CI 1.48-2.47, p < 0.00001; I² = 32%), as well as PFS(HR 1.13, 95% CI 0.81-1.57, P = 0.47; I² = 0%) and OS (HR 1.89, 95% CI 1.22-2.92, P = 0.004; I² = 0%).

Conclusion: According to our meta-analysis of 22 trials in TNBC, BRCA1/2 mutation carriers were significantly more sensitive to PBC regimens, especially in neoadjuvant and advanced therapy.

Keywords: BRCA1/2 mutation; Platinum; Triple-negative breast cancer.

Fig. 1

Flow diagram of the selection strategy.

Fig. 2

Platinum-containing neoadjuvant regimen leads to higher pCR and RCB rates in patients with TNBC with BRCA1/2 mutation. A = pCR in platinum-containing neoadjuvant regimen, B = RCB0/I in platinum-containing neoadjuvant regimen, C = pCR in cisplatin monotherapy group, D = pCR in platinum combination group. pCR: pathological complete response; RCB: residual cancer burden.

Fig. 3

Platinum-containing advanced treatment regimen improves ORR rates and survival benefits in patients with TNBC carrying BRCA1/2 mutation. A = ORR in platinum-containing advanced treatment regimen, B=PFS in platinum-containing advanced treatment regimen. C=OS in advanced treatment regimen. ORR: objective remission rate; PFS: progression-free survival; OS: overall survival.