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Emerging Strategies in HR-Positive, HER2-Negative Advanced Breast Cancer: Interpreting ESR1 Mutations and Optimizing Endocrine Therapy

Emerging Strategies in HR-Positive, HER2-Negative Advanced Breast Cancer: Interpreting ESR1 Mutations and Optimizing Endocrine Therapy

In this OncLive® News Network program, Dr. Jason Mouabbi and Dr. Seth Wander discuss evolving strategies for the management of HR-positive, HER2-negative advanced breast cancer, with a focus on the emerging role of ESR1 mutation detection and endocrine resistance. The discussion explores current treatment approaches with endocrine therapy and CDK4/6 inhibition, the clinical significance of ESR1 mutations as markers of acquired resistance, and the potential role of ctDNA-based monitoring in identifying resistance mechanisms before radiographic progression. Dr. Mouabbi and Dr. Wander review the rationale behind earlier therapeutic intervention, treatment sequencing considerations, and emerging clinical evidence evaluating endocrine therapy modification strategies, including data from key studies such as PADA-1, SERENA-6, EMERALD, and EMBER-3. The experts also discuss practical considerations for integrating biomarker testing into clinical practice, patient-centered factors such as quality of life and treatment tolerability, and future directions toward more individualized, biomarker-guided care for patients with HR-positive, HER2-negative advanced breast cancer.

Emerging Strategies in HR-Positive, HER2-Negative Advanced Breast Cancer: Interpreting ESR1 Mutations and Optimizing Endocrine Therapy

Episodes

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2 experts are featured in this series

EP. 1: Current Treatment Landscape in HR-Positive, HER2-Negative Advanced Breast Cancer

ByJason Mouabbi, MD,Seth Wander, MD, PhD

Dr. Jason Mouabbi and Dr. Seth Wander open the discussion by reviewing the evolving treatment landscape for patients with HR-positive, HER2-negative advanced breast cancer. Dr. Wander discusses the role of endocrine therapy combined with CDK4/6 inhibition as a foundational first-line treatment approach, while highlighting important patient-specific considerations such as endocrine sensitivity, prior therapy exposure, and the emergence of targeted treatment strategies. The experts discuss how advances in earlier-line therapy have improved outcomes for many patients while also contributing to an increasingly complex treatment landscape. Dr. Mouabbi emphasizes the significant impact of CDK4/6 inhibitors in transforming the management of HR-positive, HER2-negative advanced breast cancer and highlights the importance of optimizing endocrine-based treatment strategies as resistance mechanisms emerge. The discussion sets the foundation for exploring biomarker-driven approaches, including strategies aimed at addressing evolving endocrine resistance.

2 experts are featured in this series

EP. 2: Personalizing Second-Line Treatment Strategies in HR-Positive, HER2-Negative Advanced Breast Cancer

ByJason Mouabbi, MD,Seth Wander, MD, PhD

Dr. Jason Mouabbi and Dr. Seth Wander discuss considerations for treatment selection following first-line therapy in HR-positive, HER2-negative advanced breast cancer, highlighting the evolving definition of endocrine sensitivity and the growing role of precision medicine. Dr. Wander explains how the availability of newer endocrine-based therapies and targeted treatment approaches has expanded options for patients who experience disease progression. The discussion explores how molecular alterations, including ESR1 mutations, PIK3CA mutations, AKT pathway alterations, and other biomarkers, can influence treatment selection in the second-line setting. Dr. Wander also emphasizes ongoing challenges in patients without actionable alterations or those with multiple concurrent resistance mechanisms, highlighting the need for continued research to better guide sequencing strategies. The experts underscore the increasing complexity of treatment decisions as the field moves toward more individualized approaches for patients with HR-positive, HER2-negative advanced breast cancer.