[Androgen receptor-positive triple negative breast cancer: From biology to therapy]

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• A distinct subgroup of triple-negative breast cancer (TNBC) expresses the androgen receptor (AR), accounting for approximately 30% of all TNBC cases.
• These AR-positive TNBC tumors are biologically driven by AR signaling pathways and are genomically characterized by frequent PIK3CA activating mutations.
• Clinically, these tumors occur in older patients and do not exhibit a better prognosis than other TNBC subtypes.

Purpose of the Study:

• To review the current biological and clinical knowledge of AR-positive TNBC.
• To discuss the efficacy of anti-androgen therapies in this specific tumor subgroup.
• To highlight the need for predictive response factors and therapeutic combinations to enhance treatment outcomes.

Main Methods:

• Review of preclinical data and clinical trial results for anti-androgen therapies (bicalutamide, abiraterone acetate, enzalutamide).
• Analysis of the biological and genomic characteristics of AR-positive TNBC.
• Synthesis of current knowledge on treatment efficacy and future directions.

Main Results:

• Three clinical trials investigated anti-androgens, reporting clinical benefit rates in approximately 20% of patients.
• The results, while encouraging, indicate a need for improved response rates.
• AR-positive TNBC presents a unique therapeutic target amenable to non-cytotoxic strategies.

Conclusions:

• AR-positive TNBC is a biologically distinct subtype with potential for targeted anti-androgen therapy.
• Identifying predictive response factors is crucial for optimizing patient selection and treatment efficacy.
• Combination therapies hold promise for improving clinical outcomes in this challenging breast cancer subtype.