Target-Oriented Classification of Triple-negative Breast Cancer

Abstract

Background/aim: Breast cancer that is estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and human epidermal growth factor receptor-2 (HER2)-negative is termed triple-negative breast cancer (TNBC). Cytotoxic chemotherapy remains the first choice of treatment against TNBC due to lack of specific therapeutic targets. TNBC is not classified based on therapeutic targets, but recently, the development of targeted therapies - including immune checkpoint inhibitors and poly (adenosine diphosphate-ribose) polymerase inhibitors - has gained attention. This study aimed to examine a novel target-oriented TNBC classification to further facilitate targeted therapy by classifying TNBC based on the breast cancer 1 (BRCA1)-like as well as the protein expression of HER2, programmed death ligand 1 (PD-L1), androgen receptor (AR), cytokeratin 5/6, and epidermal growth factor receptor (EGFR).

Patients and methods: We enrolled 17 patients with primary TNBC who did not receive preoperative chemotherapy and underwent surgery at the Kobe University Hospital, Japan, between January 1, 2018, and July 31, 2019. Immunohistochemical staining was performed on tumor specimens, while a BRCAness test was performed using multiplex ligation-dependent probe amplification (MLPA) analysis. A BRCAness score 0.5 or higher was considered BRCA1-like.

Results: Tumors were classified as HER2-low (immunohistochemistry score 1+ or 2+ and FISH negative), PD-L1 positive, AR positive, or BRCA1-like. HER2-low, PD-L1 positive, AR positive, and BRCA1-like were detected in 11 (64.7%), 4 (23.5%), 6 (35.3%), and 6 (35.3%) samples. The tumor of only one patient could not be classified into any of these categories.

Conclusion: Almost all TNBC cases can be classified according to treatable targets.

Keywords: BRCAness; HER2-low; Triple-negative breast cancer; classification; targeted therapy.