title: Incidence of BRCA1 somatic mutations and response to neoadjuvant chemotherapy in Chinese women with triple-negative breast cancer.
abstract: BACKGROUND
  The 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.
  
  
  METHODS
  Two 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.
  
  
  RESULTS
  Eight 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.
  
  
  CONCLUSIONS
  A small subset of TNBC patients carried a BRCA1 deleterious somatic mutation; BRCA1 somatic mutation carriers are likely to respond to neoadjuvant chemotherapy.
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Breast Center, Peking University Cancer Hospital & Institute, Beijing, 100142, PR China.
authors.forename: Manxiu
authors.initials: M
authors.lastname: Li
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Breast Center, Peking University Cancer Hospital & Institute, Beijing, 100142, PR China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Breast Center, Peking University Cancer Hospital & Institute, Beijing, 100142, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Ouyang
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Breast Center, Peking University Cancer Hospital & Institute, Beijing, 100142, PR China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Li
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Breast Center, Peking University Cancer Hospital & Institute, Beijing, 100142, PR China.
authors.forename: Tianfeng
authors.initials: T
authors.lastname: Wang
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Breast Center, Peking University Cancer Hospital & Institute, Beijing, 100142, PR China.
authors.forename: Zhaoqing
authors.initials: Z
authors.lastname: Fan
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Breast Center, Peking University Cancer Hospital & Institute, Beijing, 100142, PR China.
authors.forename: Tie
authors.initials: T
authors.lastname: Fan
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Breast Center, Peking University Cancer Hospital & Institute, Beijing, 100142, PR China.
authors.forename: Benyao
authors.initials: B
authors.lastname: Lin
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Breast Center, Peking University Cancer Hospital & Institute, Beijing, 100142, PR China. Electronic address: zlxyt2@bjmu.edu.cn.
authors.forename: Yuntao
authors.initials: Y
authors.lastname: Xie
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D002681:China; D005260:Female; D019398:Genes, BRCA1; D006801:Humans; D009154:Mutation; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents
keywords: BRCA1; Neoadjuvant chemotherapy; Somatic mutation; Triple-negative breast cancer (TNBC)