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Targeted Therapies in HR+/HER2– Breast Cancer
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KEY TAKEAWAYS
- A better understanding of endocrine therapy (ET) resistance mechanisms has guided the development of targeted combination therapies for HR-positive/HER2-negative (HR+/HER2–) breast cancer, but resistance evolution complicates long-term disease management.
- The CDK4/6 inhibitors palbociclib, ribociclib, and abemaciclib have
become foundational in the first-line treatment of HR+/HER2– breast
cancer, significantly improving survival outcomes. - Emerging next-generation targeted therapies, such as capivasertib
and elacestrant, target resistance mechanisms like ESR1 mutations
and alterations in the PI3K/AKT/mTOR pathway. These biomarker driven
approaches are critical but require testing standardization
across institutions. - Antibody-drug conjugates (ADCs), such as trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan, represent a paradigm shift in treating ET-refractory metastatic breast cancer, showing efficacy even in heavily pretreated populations.
- Despite improved outcomes with targeted therapies and their combinations, challenges remain regarding their optimal sequencing and rechallenge strategies post progression in the HR+/HER2– breast cancer treatment algorithm.
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