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 |
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| Authors: | Chuan‐Gui Song Zhi‐Gang Zhuang A‐Yong Cao Hong Ling Ke‐Da Yu Shan Li Meng‐Hong Sun Xiao‐Yan Zhou Wei Huang Zhi‐Ming Shao |
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| Affiliation: | 1. Department of Breast Surgery, Affiliated Union Hospital, Fujian Medical University, Fuzhou, People's Republic of China;2. Department of Breast Surgery, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China;3. Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China;4. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China;5. Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China;6. 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 |
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| 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. |
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| Keywords: | BRCA germline mutations breast cancer Chinese next‐generation sequencing |
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