Systemic Therapy for HER2-Positive Metastatic Breast Cancer: Current and Future Trends

Area of Science:

• Oncology
• Pharmacology

Background:

• HER2-positive breast cancer (BC) accounts for ~20% of BC cases.
• This subtype historically had poor survival and high metastasis risk before targeted therapies.
• Standard treatment involved dual blockade with trastuzumab and pertuzumab, followed by TDM-1.

Purpose of the Study:

• To review advancements in HER2-targeted therapies for breast cancer.
• To highlight new therapeutic options and future perspectives for HER2-positive BC.
• To address ongoing challenges such as treatment resistance and brain metastases.

Main Methods:

• Review of recent clinical data and therapeutic advancements.
• Analysis of new-generation antibody-drug conjugates (ADCs) and other targeted agents.
• Discussion of treatment paradigms and future research directions.

Main Results:

• New HER2-targeted therapies, particularly novel ADCs like trastuzumab deruxtecan, have significantly improved clinical outcomes.
• Trastuzumab deruxtecan has emerged as a new standard of care in the second-line setting, surpassing TDM-1.
• Despite progress, challenges including disease progression, resistance, and brain metastases remain significant issues.

Conclusions:

• The treatment landscape for HER2-positive BC has been revolutionized by novel targeted therapies.
• While outcomes have improved, further research is needed to overcome resistance and manage metastases.
• Future strategies will likely involve combination therapies and personalized approaches to address tumor heterogeneity.