Abstract P4-03-10: Identifying germline APOBEC3B deletion using hereditary cancer panel in Korean patients with operable breast cancer

Abstract

Abstract Background: APOBEC3B is a cytosine deaminase implicated in host immune defense to virus and mutagenesis in cancer. Germline APOBEC3B deletion is known as risk factors for breast cancer with hypermutation and immune activation from previous database-based studies. This study was aimed to evaluate the incidence of germline APOBEC3B deletion in Korean patients with operable breast cancer. Method: The copy number variants of germline APOBEC3B deletion was analyzed from leukocyte DNA of 103 breast cancer patients whose bloods were collected in 2009 for pharmacogenomic study at Seoul National University Bundang Hospital. Hybrid-capture based next-generation sequencing panel targeting 53 hereditary cancer genes were used. We also measured tumor infiltrating lymphocytes (TILs) and programmed cell death-ligand 1 (PD-L1) expression in tumor or immune cell with a rabbit monoclonal antibody (E1L3N). Results: Median age of breast cancer diagnosis was 46 (25-72). In APOBEC3B deletion analysis, 10 (9.7%), 36 (35.0%), and 57 (55.3%) patients were identified as two-copy deletion (A3Bdel/del), one-one copy deletion (A3Bdel/wt) and no deletion (A3Bwt/wt), respectively. In non-APOBEC3B analysis, 9 (8.7%) patients were identified as pathogenic variant: RAD51D(n=1), GJB2(n=1), BRCA1(n=1), BRCA2 (n=2), ATM(n=1), USH2A(n=1), RET(n=1), BARD1(n=1). We observed no significant association between germline APOBEC3B deletion with any clinicopathologic features of breast cancer such as age, family history of cancer, and bilateral breast cancer. Triple-negative subtype was associated with A3Bwt/wt Tumors (35.1% in A3Bwt/wt vs. 5.6% in A3Bdel/wt vs20% in A3Bdel/del; P=0.018). After a median follow-up time of 92.8 months, APOBEC3B deletion was not predictive of recurrence or survival. In patients with sufficient tumor samples for the assessment of TIL (n=63) and PD-1 (n=71), A3Bdel/del tumor was associated with higher TILs (>10%) than other tumor types (6/7 patients in A3Bdel/del vs. 13/24 in A3Bdel/wt vs. 15/32 in A3Bwt/wt: Fisher's exact test in A3Bdel/del, P=0.029). However, PD-L1 expression was not associated with APOBEC3B deletion status (1/7 patients >1% PD-L1 in A3Bdel/del vs. 4/26 in A3Bdel/wt vs. 8/38 in A3Bwt/wt: P=0.901). Germline APOBEC3B deletion and TILs (n=63) TIL (0-10%)TIL (>10%)TotalA3B(wt/wt)17 (53.1%)15 (46.9%)32A3B(del/wt)11 (45.8%)13 (54.2%)24A3B(del/del)1 (14.3%)6 (85.7%)7 Conclusion: We identified germline APOBEC3B deletion in 9.7% of Korean patients with operable breast cancer. The relationship between A3Bdel/del tumor and high TILs suggests that these tumors might be potential candidates for future immunotherapy. Citation Format: Kim SH, Koung Jin S, Kim YJ, Ahn S, Park SY, Chae SM, Kang E, Kim E-K, Kim IA, Kim JH. Identifying germline APOBEC3B deletion using hereditary cancer panel in Korean patients with operable breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-03-10.