Immunotherapy (IO) has been recently introduced in triple-negative breast cancer (TNBC) therapeutic algorithm, however no predictive biomarkers beyond PDL-1 expression demonstrated utility in clinical practice. BRCA mutations account for 15-20% of TNBC, with a positive association with platinum response and an inflammatory background on tumor tissue. Preclinical evidences demonstrated a lack of T-cell activation in BRCA-mutant (BRCAm) tumors due to an HLA machinery defects, but no subgroup effects were observed in IO pivotal trials evaluating chemotherapy-IO combinations.
We retrospectively evaluated the effect of germline BRCA mutations in consecutive BC patients underwent any-line IO-only treatment in phase I/II trials at Fondazione IRCCS Istituto Nazionale dei Tumori in Milan. Only mutations evaluated as pathogenic after genetic counselling were considered. IO treatment included PD(L)1, LAG3 and ICOS inhibitors, single agents or in combination. Statistical analysis were performed with RStudio software v2022.07.0.
Of 39 pts treated with IO from June 2016 to September 2022, 22 had available germline BRCA status. 4 pts exhibited mutations in
In our small retrospective cohort, the presence of a pathogenic mutation in
Fondazione IRCCS Istituto Nazionale dei Tumori, Milan.
Has not received any funding.
M. Di Nicola: Non-Financial Interests, Institutional, Principal Investigator: AMGEN, BMS, Novartis, Roche, Sanofi, Incyte, Beigene, Genentech, Merck. F.G.M. De Braud: Financial Interests, Personal, Advisory Board: Ignyta, BMS, Daiichi Sankyo, Pfizer, Incyte, Roche; Financial Interests, Personal, Invited Speaker: MSD, Bayer, ACCMED, Merck; Non-Financial Interests, Institutional, Principal Investigator: Novartis, Celgene, Tesaro. All other authors have declared no conflicts of interest.