Triple-negative breast cancer: from none to multiple therapeutic targets in two decades

Area of Science:

• Oncology
• Molecular Biology
• Cancer Therapeutics

Background:

• Triple-negative breast cancer (TNBC) presents a significant clinical challenge due to its aggressive nature and lack of targeted therapies.
• TNBC is characterized by molecular heterogeneity, necessitating a deeper understanding of its subtypes for effective treatment.
• The absence of estrogen receptors, progesterone receptors, and HER2 overexpression defines TNBC, limiting conventional treatment options.

Purpose of the Study:

• To provide a systematic review of the molecular underpinnings of triple-negative breast cancer.
• To explore emerging therapeutic strategies and biomarkers for TNBC.
• To highlight the paradigm shift towards immunotherapy and targeted drug development in TNBC.

Main Methods:

• Systematic literature review of TNBC research over the past two decades.
• Analysis of molecular subtypes and their clinical implications.
• Evaluation of current and novel therapeutic approaches, including immunotherapy, PARP inhibitors, and antibody-drug conjugates (ADCs).

Main Results:

• TNBC harbors a higher frequency of germline BRCA mutations, offering a target for PARP inhibitors through synthetic lethality.
• Identification of novel molecular targets has paved the way for advanced therapies like ADCs.
• Immunotherapy has emerged as a promising strategy, fundamentally changing the treatment landscape for TNBC.

Conclusions:

• A comprehensive understanding of TNBC's molecular complexity is crucial for developing personalized treatment strategies.
• Targeted therapies, including PARP inhibitors and ADCs, alongside immunotherapy, represent significant advancements in managing TNBC.
• Continued research into biomarkers is essential for optimizing patient selection and treatment efficacy in TNBC.