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Identifying germline APOBEC3B deletion and immune phenotype in Korean patients with operable breast cancer

Abstract

Background

Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3B (APOBEC3B) is implicated in anti-viral immune response and cancer mutagenesis. Germline APOBEC3B deletion is associated with increased susceptibility to breast cancer. We aimed to evaluate the association between germline APOBEC3B deletion and clinical phenotypes of breast cancer in Korean patients with operable breast cancer.

Methods

Mononuclear blood cell DNA of 103 patients with operable breast cancer was collected at Seoul National University Bundang Hospital in 2009. The DNA was sequenced to analyze APOBEC3B deletion status. Further, tumor-infiltrating lymphocytes (TILs) and programmed cell death-ligand 1 (PD-L1) expression in tumor cells were measured using immunohistochemistry.

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. For other cancer susceptibility gene alterations, 9 (8.7%) patients were identified as pathogenic variants: 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. Further, according to follow-up observations, APOBEC3B deletion was not predictive of disease-free survival. In ER+ subtype, a trend toward better survival was observed in patients with A3Bdel/del genotype as compared to patients with A3Bdel/wt and A3Bwt/wt genotype (log-rank, P = 0.25). In patients with sufficient tumor samples for the assessment of TIL (n = 63) and PD-L1 (n = 71), the A3Bdel/del genotype was significantly associated with high TILs (> 10%) than other tumor genotypes (6/7 patients in A3Bdel/del vs. 13/24 in A3Bdel/wt vs. 15/32 in A3Bwt/wt: Fisher’s exact test, 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).

Conclusion

We identified germline APOBEC3B deletion in 9.7% of Korean patients with operable breast cancer. The relationship between A3Bdel/del genotype and high TILs suggests that patients carrying this genotype could be potential candidates for immunotherapy.

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Acknowledgements

We would like to thank Editage (www.editage.co.kr) for English language editing. Note on previous publication: This manuscript was partly presented in part at the San Antonio Breast Cancer Symposium (SABCS); San Antonio, TX, December 4–8, 2018 in a poster presentation.

Funding

This study was funded by the Grants from the SNUBH Research Fund (Grant Number 13-2017-002 to SH Kim).

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Correspondence to Jee Hyun Kim.

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The authors declare that they have no conflict of interest.

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All procedures performed in studies involving human participants were in accordance with the Ethical Standards of the Institutional and/or National Research Committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study was approved by the Institutional Review Boards of Seoul National University Bundang Hospital (Approval No. B-1711-430-301).

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Kim, S.H., Ahn, S., Suh, K.J. et al. Identifying germline APOBEC3B deletion and immune phenotype in Korean patients with operable breast cancer. Breast Cancer Res Treat 183, 697–704 (2020). https://doi.org/10.1007/s10549-020-05811-2

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Keywords

  • APOBEC3B
  • TIL
  • PD-L1
  • Germline
  • Immune phenotype