The effect of neoadjuvant platinum-based chemotherapy in BRCA mutated triple negative breast cancers -systematic review and meta-analysis

BACKGROUND: Triple negative breast cancers (TNBC) are associated with an aggressive clinical course, earlier recurrence and short survival. BRCA – mutated tumours represent up to 25% of all TNBC. BRCA status is being studied as a predictive biomarker of response to platinum agents. However, the predictive role of BRCA status is still uncertain in this setting. Since TNBC is a very heterogeneous group of diseases, it is important to identify subsets of TNBC patients that may benefit from platinum-based therapy. This study aims to establish if the presence of a germline BRCA mutation in women with TNBC improves the pathologic complete response (pCR) after neoadjuvant chemotherapy with platinum compounds. METHODS: An extensive literature search was performed in MEDLINE, EMBASE and LILACS databases, WHO (WHO International Clinical Trials Registry Platform) and the Cochrane Controlled Trials Register Database, for online trial registries and conference proceedings. The measurement of pCR was assessed by pathology review of breast specimen and lymph nodes. RESULTS: The overall OR was computed using random effects models. Seven studies were included, comprising a total of 808 TNBC patients, among which 159 were BRCA mutated. Among mutated TNBC patients, 93 (93/159; 58.4%) achieved pCR, while 410 wildtype patients (410/808; 50.7%) showed pCR (OR 1.459 CI 95% [0.953–2.34] p = 0.082) although this result did not reach statistical significance. CONCLUSIONS: This meta-analysis shows that the addition of platinum to chemotherapy regimens in the neoadjuvant setting increases pCR rate in BRCA – mutated as compared to wild-type TNBC patients. However, this trend did not achieve statistical significance. TRIAL REGISTRATION: CRD42018092341