Non-BRCA germline pathogenic variants and response to neoadjuvant systemic therapy in triple-negative breast cancer patients enrolled in a prospective clinical trial.
Summary
This prospective study investigated the prevalence of non-BRCA germline pathogenic variants (PVs) and their impact on response to neoadjuvant therapy (NAT) in patients with triple-negative breast cancer (TNBC). Among 184 patients, 36% harbored PVs in pan-cancer susceptibility genes, including variants in 31 genes not previously found in other US cohorts. Patients received NAT with doxorubicin, cyclophosphamide, paclitaxel, and carboplatin, with or without immunotherapy or targeted therapy. Despite this high prevalence, the presence of these non-BRCA germline PVs was not associated with a significant difference in pathologic complete response (pCR) or radiologic response. The findings suggest the utility of multigene panels for screening but indicate that these variants are not predictive of NAT response in TNBC.
Analysis
This research is crucial as it highlights a substantial prevalence of non-BRCA germline pathogenic variants in triple-negative breast cancer patients, underscoring the importance of broader genetic screening using multigene panels. However, the lack of association between these variants and the response to standard neoadjuvant chemotherapy provides essential clinical information. This means that these genetic alterations cannot be used as predictive biomarkers for the efficacy of current neoadjuvant treatment, which helps avoid unjustified changes in therapeutic strategy and better counsel patients on their treatment expectations.