Germline Mutations Related to Complete Remission after Neoadjuvant Chemotherapy in Patients with Triple-negative Breast Cancer

Background : Triple-negative breast cancer (TNBC) is a frequent phenotype of BRCA-mutant tumors. Tumors with BRCAness may show characteristics of BRCA-mutant tumors and respond to similar treatments. Next-generation sequencing (NGS) is an efficient and cost-effective method for simultaneously sequencing multiple cancer susceptibility genes, surpassing the conventional Sanger testing. Methods : A total of 148 women with TNBC were recruited from December 2015 to November 2018 at Yonsei Cancer Center. Of them, 103 patients received neoadjuvant chemotherapy (NCT). The targeted genes related to hereditary cancers were sequenced using the 65-gene germline NGS (gNGS) panel pathogenic and likely pathogenic variants (P&LPs) were determined by Sanger sequencing. We examined the occurrence of pathologic complete remission (ypCR) in patients with P&LPs. Results : The patients’ median age was 47 years (range, 27–69 years). Twenty (13.7%) of 148 patients had P&LP in six genes, including BARD1 (n=2), BRCA1 (n=9), BRCA2 (n=5), CHEK2 (n=1), RAD51C (n=1), and RAD51D (n=2). Among the 103 patients with NCT, 43 (28.9%) achieved ypCR (P&LPs; 9 individuals vs. non-variants; 34 individuals). Among the 103 patients with NCT, 14 (9.3%) had P&LPs. Nine of 14 patients with P&LPs, including BARD1 (n=2), BRCA1 (n=4), BRCA2 (n=1), RAD51 C (n=1), and RAD51D (n=1), achieved ypCR ( P = .066). Conclusion : Germline P&LP mutations in TNBC patients can be detected by gNGS. This panel test can identify BRCA and BRCAness mutations that may predict ypCR in TNBC.