Abstract 214P
Background
Breast cancer (BC) is one of the most prevalent malignancies throughout the world. Important therapeutic progress has been achieved over the past decade, and the identification of genomic alterations in the homologous recombination repair (HRR) pathway sensitizes tumors to therapeutics such as PARP inhibitors and platinum-based chemotherapy. Here we evaluated the characteristics of HRR related gene mutations in patients with different molecular subtypes of BC.
Methods
A total of 121 patients with BC were enrolled into the study. All samples were collected and detected by DNA based NGS with a 1021 gene panel which containing 36 HRR genes (CHEK1/2, BRCA1/2, BRIP1, CDK12, ATM/ATR, FANCA/C/D2/E/F/G/L/M, MRE11A, NBN, RAD50/51/52, RAD51B/C/D et al).
Results
121 patients (75 hormone receptor [HR]+, 29 triple-negative BC [TNBC], 17 human epidermal growth factor receptor 2 [HER2]+) were included. The proportions of HRR gene mutations in 3 subtypes of BC were 44.0% (33/75, HR+), 34.5% (10/29, TNBC) and 88.2% (15/17, HER2+), respectively. HRR genomic heterogeneity was found in the different molecular subtypes of BC. The top 5 mutated HRR genes in HR+ BC were BRCA2 (13/33, 39.4%), CDK12 (6/33, 18.2%), BRCA1 (5/33, 15.2%), NBN (5/33, 15.2%), ATM (4/33, 12.1%). In TNBC, the top 6 mutated HRR genes were BRCA1 (3/10, 30.0%), NBN (2/10, 20.0%), BRCA2 (1/10, 10.0%), ATRX (1/10, 10.0%), PALB2 (1/10, 10.0%). The most frequent HRR genetic alteration involve in HER2+ BC were CDK12 (9/15, 60.0%), BRIP1 (4/15, 26.7%), BRCA1 (3/15, 20.0%), BRCA2 (2/15, 13.3%), ATRX (1/15, 6.7%). Among the 65 HR+ BC patients receiving adjuvant therapy, 9 (9/65, 13.9%) patients received platinum-based adjuvant therapy. The medium follow-up time was 34 m (range 18-68 m). For the 3 patients who had relapsed, the 2 patients with HRR gene mutations had longer DFS (48 m and 68 m, respectively) than the other one without HRR gene mutations had shorter DFS (18 m).
Conclusions
In terms of HRR gene mutations, HR+, TNBC and HER2+ BC have different mutation landscape. Mutations in HRR genes may serve as a biomarker for platinum-based adjuvant therapy for HR+ BC patients, which warrants further studies.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.