Correlation between germline mutations in homologous recombination repair related genes and clinical characteristics in Chinese patients with breast cancer.

Abstract

e12536 Background: Poly (ADP-ribose) polymerase inhibitors treatment strategies for BRCA germline mutations in breast cancer have been recommended. A comprehensive understanding of the relationship between germline mutations of HRR pathway related genes and the clinical characteristics of breast cancer will help further accurate diagnosis and treatment of breast cancer. Methods: A total of 613 female consecutive breast cancer patients from Breast Surgery of Harbin Medical University Cancer Hospital of Harbin Medical University Cancer Hospital were enrolled retrospectively. Clinical characteristics were collected and next-generation sequencing was performed using blood samples of participants to identify pathogenic/likely pathogenic (P/LP) germline mutations in 32 HRR-related genes ( gHRR ). The survival analysis included 55 patients with over 3 years of follow-up, comprising 21 triple-negative breast cancer (TNBC) patients and 20 Luminal B patients. Results: Pathogenic and like pathogenic mutations were identified in 16.64 % of patients among the 613 breast cancer patients. Of these, 11.59 % of patients carried a BRCA1 or BRCA2 mutation (6.04% in BRCA1 and 5.55% in BRCA2 ), 5.71% carried other breast cancer g HRR . Interestingly, Luminal B(HER2-negtaive) breast cancers had the highest prevalence of g HRR mutations (24/113, 21.24%,) and as for hormone receptor-positive (HR + ) patients, the mutation rate were 18.59% (37/199). TNBC showed a 19.55% (42/216) mutation rate. Whereas HER2 positive breast cancers had the lowest mutations in g HRR (1/20, 5%). We further compared HR+ and TNBC breast cancer and found no significant difference in g HRR mutation rates between patients aged 40 or younger and those older than 40. According to the multivariate logistic regression in HR+ patients, those with age ≤ 40 ( p = 0.0337) were more likely to be g HRR mutation. Although not statistically significant, patients with lymphatic invasion ( p = 0.078) appeared more likely to have g HHR mutation. In addition, gHRR mutation carriers had a significant worse disease-free survival [hazard ratio (HR) 3.70; 95% confidence interval (CI) 0.67–20.46; p = 0.032] than did non-carriers in the luminal B groups, whereas no significant difference in survival was found between g HRR mutation carriers and non-carriers among TNBC. Conclusions: In this study, we have performed the systematic collection and the pathogenicity interpretation of g HHR variants in the Chinese breast cancer. Onset younger than or equal to 40 years of age, lunamial B and TNBC patients may be more likely to be recommended for detecting P/LP germline mutations in HRR genes. Keywords: Breast Cancer; gHRR mutation; luminal B, age.