Target-Oriented Classification of Triple-negative Breast Cancer

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.