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

Abstract

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.

• Authors: Shuyan Sheng, Ye Xu, Yonghai Guo, Lu Yao, Li Hu, Tao Ouyang, Jinfeng Li, Tianfeng Wang, Zhaoqing Fan, Tie Fan, Benyao Lin, Yuntao Xie
• Journal: International journal of cancer (Int J Cancer) Vol. 146 Issue 2 Pg. 487-495 (01 15 2020) ISSN: 1097-0215 [Electronic] United States
• PMID: 31119730 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 UICC.

Chemical References

• Anthracyclines
• Biomarkers, Tumor
• Bridged-Ring Compounds
• TP53 protein, human
• Taxoids
• Tumor Suppressor Protein p53
• taxane

Topics

• Adult
• Aged
• Anthracyclines (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Asian People (genetics)
• Biomarkers, Tumor (genetics)
• Breast Neoplasms (drug therapy, genetics)
• Bridged-Ring Compounds (therapeutic use)
• Cohort Studies
• Female
• Germ-Line Mutation (genetics)
• Humans
• Middle Aged
• Neoadjuvant Therapy (methods)
• Prevalence
• Taxoids (therapeutic use)
• Tumor Suppressor Protein p53 (genetics)
• Young Adult