Incidence of BRCA1 somatic mutations and response to neoadjuvant chemotherapy in Chinese women with triple-negative breast cancer

• We determine BRCA1 somatic mutations in a relatively large cohort of triple-negative breast cancers (TNBC).
• Approximately 3.9% of TNBC patients carried a BRCA1 deleterious somatic mutation.
• TNBC patients with a BRCA1 deleterious somatic mutation are likely to respond to neoadjuvant chemotherapy.

BackgroundThe prevalence of BRCA1 somatic mutations status in triple-negative breast cancer (TNBC) has not been well documented. The aims of this study were to determine the frequency of BRCA1 somatic mutations and to investigate the association between BRCA1 deleterious somatic mutation status and response to neoadjuvant chemotherapy in women with TNBC.MethodsTwo hundred and five TNBC patients without BRCA1 germline mutations were enrolled in this study. Fresh tumor tissues were available for this cohort of 205 patients, including 112 patients with fresh core needle biopsy tumor tissues before treatment and 93 patients with fresh tumor tissues procured after surgery. BRCA1 somatic mutations were determined in the tumor samples using PCR-direct sequencing assay. Among the 112 patients with core needle biopsy samples, 97 patients received neoadjuvant chemotherapy.ResultsEight patients (3.9%) carried a BRCA1 pathogenic somatic mutation in this cohort of 205 TNBC patients. These eight BRCA1 deleterious somatic mutations included five frameshift or nonsense mutations (c.191_212del22, c.1664delA, c.4674_4675 + 17del, c.3671_3672insTTCC, c.1162A > T), one splicing site mutation (c.134 + 2T > G) and two missense mutations (c.5511G > C and c.286G > A). No significant differences in tumor characteristics between BRCA1 deleterious somatic mutation carriers and non-carriers were observed. The pCR (pathologic complete response) rate was 32.0% in the 97 patients who received neoadjuvant chemotherapy. BRCA1 deleterious somatic mutation carriers (n = 5) had a higher pCR rate than did non-carriers (n = 92) (BRCA1 carriers vs non-carriers, 60.0% vs 30.4%, P = 0.32), although it did not reach a significance due to a small sample size.ConclusionsA small subset of TNBC patients carried a BRCA1 deleterious somatic mutation; BRCA1 somatic mutation carriers are likely to respond to neoadjuvant chemotherapy.