Human epidermal growth factor receptor 2 (HER2)-positive and hormone receptor-positive breast cancer: new insights into molecular interactions and clinical implications

Area of Science:

• Oncology
• Molecular Biology
• Translational Medicine

Background:

• Metastatic breast cancer treatment often involves anti-HER2 agents and endocrine therapy.
• Current clinical practice favors chemotherapy with anti-HER2 agents for HER2-positive, hormone receptor-positive (HR+) breast cancer.
• This approach is used regardless of HR status, perceiving HER2-positive tumors as a homogeneous group.

Purpose of the Study:

• To review the biological heterogeneity of HER2-positive breast cancer based on HR status.
• To explore the cross-talk between HER2 and HR pathways and its role in therapeutic resistance.
• To discuss novel therapeutic strategies targeting these pathways.

Main Methods:

• Literature review of biological and clinical data.
• Analysis of the interplay between HER2 and hormone receptor signaling.
• Evaluation of emerging treatment strategies.

Main Results:

• HER2-positive breast cancers exhibit heterogeneity, partly influenced by HR co-expression.
• The cross-talk between HER2 and HR pathways impacts resistance to both anti-HER2 and endocrine therapies.
• Chemotherapy may be overtreatment in certain HER2-positive breast cancer cases.

Conclusions:

• The paradigm of treating all HER2-positive breast cancers uniformly needs re-evaluation.
• Understanding HR status is crucial for tailoring treatment strategies.
• Novel therapeutic approaches combining targeted therapies offer potential for improved outcomes.