title: The spectrum of BRCA mutations and characteristics of BRCA-associated breast cancers in China: Screening of 2,991 patients and 1,043 controls by next-generation sequencing.
abstract: To characterize the prevalence of BRCA mutations and characteristics of BRCA carriers in China and to update the clinical recommendations for BRCA testing, we conducted a wide screen for BRCA mutations using next-generation sequencing (NGS). A total of 4,034 Chinese subjects were screened for germline BRCA1/2 mutations, including 2,991 breast cancer patients and 1,043 healthy individuals from the community enrolled as controls. We developed an NGS-based approach to perform BRCA1/2 screening. BRCA mutations were identified in 9.1% (232/2,560) of cases with at least one risk factor, in 3.5% (15/431) of sporadic patients and in 0.38% (4/1,043) of healthy controls. The mutation frequency ranged from 8.9 to 15.2% in cohorts with a single risk factor to 16.6-100% in groups with multiple risk factors. We identified 70 novel BRCA mutations. A high frequency of BRCA1 c.5470_5477del was detected, accounting for 13.9% (16/115) of the BRCA1 mutations detected in our study. Clinical characteristics such as family history, invasive carcinoma, negative human epidermal growth factor receptor 2 (HER2), high Ki67 index, lymph node status, and high tumour grade were closely related to BRCA mutations. BRCA2 carriers had poorer disease-free survival among HER2- or hormone receptor-positive patients (hazard ratio = 1.892; 95% confidence interval: 1.132-3.161; p = 0.013). This study shows that BRCA mutation carriers could be frequently identified among breast cancer patients with multiple risk factors. Importantly, we established an NGS-based pipeline for BRCA1/2 testing in clinical practice and strongly suggest that breast cancer patients of premier- and moderate-grade risks receive BRCA1/2 mutations testing in China.
authors.affiliation: Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
authors.forename: Guan-Tian
authors.initials: GT
authors.lastname: Lang
authors.affiliation: Department of Genetics, Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center and Shanghai Industrial Technology Institute (SITI), Shanghai, People's Republic of China.
authors.forename: Jin-Xiu
authors.initials: JX
authors.lastname: Shi
authors.affiliation: Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Genetics, Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center and Shanghai Industrial Technology Institute (SITI), Shanghai, People's Republic of China.
authors.forename: Chen-Hui
authors.initials: CH
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.
authors.forename: Ling
authors.initials: L
authors.lastname: Shan
authors.affiliation: Department of Breast Surgery, Affiliated Union Hospital, Fujian Medical University, Fuzhou, People's Republic of China.
authors.forename: Chuan-Gui
authors.initials: CG
authors.lastname: Song
authors.affiliation: Department of Breast Surgery, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Zhuang
authors.affiliation: Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
authors.forename: A-Yong
authors.initials: AY
authors.lastname: Cao
authors.affiliation: Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Ling
authors.affiliation: Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
authors.forename: Ke-Da
authors.initials: KD
authors.lastname: Yu
authors.affiliation: Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
authors.forename: Shan
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.|Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.
authors.forename: Meng-Hong
authors.initials: MH
authors.lastname: Sun
authors.affiliation: Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.|Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Zhou
authors.affiliation: Department of Genetics, Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center and Shanghai Industrial Technology Institute (SITI), Shanghai, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
authors.forename: Zhi-Ming
authors.identifier: 0000-0001-8781-2455
authors.initials: ZM
authors.lastname: Shao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D002681:China; D018572:Disease-Free Survival; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006579:Heterozygote; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human
keywords: BRCA; Chinese; breast cancer; germline mutations; next-generation sequencing