Current Treatment Approaches in HER2+ Metastatic Breast Cancer

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Panelists discussed how evolving strategies in HER2-positive metastatic breast cancer are shifting toward more personalized maintenance approaches, including the integration of CDK4/6 inhibitors and endocrine therapy, with growing interest in chemotherapy-free options for select patients.

The current treatment landscape for HER2-positive metastatic breast cancer has evolved significantly, with recent updates further refining patient care strategies. Historically, the CLEOPATRA regimen—trastuzumab, pertuzumab, and docetaxel—has been the preferred first-line therapy, offering substantial progression-free and overall survival benefits. While this standard remains foundational, ongoing discussions now include how to personalize maintenance strategies post-chemotherapy, particularly for patients who are hormone receptor positive. There is increasing consideration of adding CDK4/6 inhibitors, such as palbociclib, alongside endocrine therapy and HER2-directed agents for maintenance, especially in patients demonstrating good initial response.

Recent trial data have shown that combining HER2-targeted therapy with endocrine therapy and CDK4/6 inhibition can significantly prolong progression-free survival, even approaching a 15-month benefit in some cases. However, real-world implementation faces challenges such as inconsistent insurance approvals. Clinicians have begun using creative strategies, including submitting trial data screenshots to support access. Still, patient selection remains nuanced. Many oncologists reserve these maintenance strategies for patients who have completed six months of induction chemotherapy with a strong response, though approaches may differ depending on performance status and disease biology.

Looking ahead, the field continues to explore whether some patients can avoid traditional chemotherapy altogether. In carefully selected individuals, particularly older or frail patients, dual HER2 blockade with endocrine therapy may offer a gentler and still effective alternative. Trials and real-world experiences suggest that nonchemotherapy approaches can yield favorable outcomes for select groups. As newer agents and maintenance strategies emerge, treatment sequencing will likely shift. Ongoing refinement in therapy decisions will depend on patient characteristics, evolving clinical trial data, and increased understanding of tumor biology, ultimately aiming to balance efficacy with quality of life in HER2-positive metastatic breast cancer.

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