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Updated: Jul 12, 2025
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Target-Oriented Classification of Triple-negative Breast Cancer
Sachiko Mizumoto1, Sachiko Inubushi2, Mayuko Miki1
1Division of Breast Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
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.
Insights
This study introduces a new classification for triple-negative breast cancer (TNBC) based on specific protein expressions and BRCA1-like status. This approach aims to identify treatable targets for TNBC, improving patient outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Triple-negative breast cancer (TNBC) lacks specific therapeutic targets, making cytotoxic chemotherapy the primary treatment.
- Recent advancements in targeted therapies, including immune checkpoint inhibitors and PARP inhibitors, highlight the need for novel TNBC classifications.
- Current TNBC classification does not align with therapeutic targets, necessitating a new approach.
Purpose of the Study:
- To develop and examine a novel target-oriented classification for triple-negative breast cancer (TNBC).
- To facilitate targeted therapy development by classifying TNBC based on BRCA1-like status and protein expression of HER2, PD-L1, AR, cytokeratin 5/6, and EGFR.
- To identify potential therapeutic targets within TNBC subtypes.
Main Methods:
- Enrolled 17 patients with primary TNBC who underwent surgery without preoperative chemotherapy.
- Performed immunohistochemical staining on tumor specimens for protein expression analysis.
- Utilized multiplex ligation-dependent probe amplification (MLPA) for BRCAness testing, defining BRCA1-like as a score ≥ 0.5.
Main Results:
- Classified TNBC tumors based on HER2-low, PD-L1 positive, AR positive, or BRCA1-like status.
- Detected HER2-low in 64.7%, PD-L1 positive in 23.5%, AR positive in 35.3%, and BRCA1-like in 35.3% of samples.
- Successfully classified all but one patient's tumor into at least one of the defined categories.
Conclusions:
- The proposed target-oriented classification effectively categorizes almost all triple-negative breast cancer (TNBC) cases.
- This classification system identifies treatable targets within TNBC, paving the way for personalized treatment strategies.
- The findings support the potential for improved therapeutic strategies in TNBC based on molecular profiling.
