Prevalence and clinical impact of TP53 germline mutations in Chinese women with breast cancer

• Published in: International journal of cancer Vol. 146; no. 2; pp. 487 - 495
• Main Authors: Sheng, Shuyan, Xu, Ye, Guo, Yonghai, Yao, Lu, Hu, Li, Ouyang, Tao, Li, Jinfeng, Wang, Tianfeng, Fan, Zhaoqing, Fan, Tie, Lin, Benyao, Xie, Yuntao
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 15.01.2020; Wiley Subscription Services, Inc
• Subjects: Adult; Aged; Anthracycline; Anthracyclines - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Asian Continental Ancestry Group - genetics; Biomarkers, Tumor - genetics; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Bridged-Ring Compounds - therapeutic use; Cancer; Carboplatin; Chemotherapy; Cohort Studies; Female; Germ-Line Mutation - genetics; Humans; Medical research; Middle Aged; Mutation; neoadjuvant chemotherapy; Neoadjuvant Therapy - methods; p53 Protein; Prevalence; Sequences; Survival; Taxanes; Taxoids - therapeutic use; TP53 germline mutation; Tumor Suppressor Protein p53 - genetics; Young Adult; TP53 germline mutation; neoadjuvant chemotherapy; breast cancer; survival
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.32424

The prevalence and clinical relevance of TP53 germline mutations in a large unselected breast cancer series are largely unknown. Here, we determined TP53 germline mutations in a large cohort of 10,053 unselected breast cancer patients through multigene panel‐based next‐generation and/or Sanger sequencing assays. We found that 0.5% of patients (50 cases) carried a pathogenic TP53 germline mutation in this large series of 10,053 unselected breast cancer patients, and the prevalence of TP53 germline mutation was 3.8% in very early onset breast cancer (age ≤30 years) in this large cohort. TP53 mutation carriers were significantly more likely to have early onset cancer (p < 0.001) and bilateral breast cancer (p = 0.03), they and were significantly more likely to respond to carboplatin‐based neoadjuvant chemotherapy compared to anthracycline‐ or taxane‐based regimen in terms of pathologic complete response (50% vs. 0%, p = 0.006). At the median follow‐up of 54 months, TP53 mutation was an independent unfavorable factor for recurrence‐free survival (RFS), distant recurrence‐free survival (DRFS), and overall survival (OS) (RFS, adjusted hazard ratio [HR]: 2.24, 95% confidence interval [CI]: 1.15–4.33, p = 0.02; DRFS, adjusted HR: 2.73, 95% CI: 1.41–5.30, p = 0.003; OS, adjusted HR: 4.60, 95% CI: 2.26–9.41, p < 0.001) in multivariate analyses. Our study suggested that TP53 germline mutations occur more frequently in very early onset unselected breast cancer patients; and TP53 germline mutation carriers have a very poor survival and may benefit from carboplatin‐based neoadjuvant chemotherapy in unselected breast cancer patients. What's new? Carriers of germline mutations of the tumor suppressor TP53 have a 100‐times higher risk to develop cancer, often in multiple organs, but the clinical relevance of the mutations in women with breast cancer remains unclear. Here, the authors examined more than 10,000 Chinese women with breast cancer and found 0.5% (50 cases) carried a pathogenic TP53 germline mutation. Carriers more often had early‐onset disease, a poorer survival and responded to carboplatin‐based neoadjuvant chemotherapy, the latter a relevant therapeutic outcome of testing for mutation carriers.