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Optimizing Oral SERD Therapy in Metastatic Breast Cancer: Translating Biomarker Insights Into Patient-Centered Care

Clinical Thought

In this commentary, advanced practice providers who are experts in breast cancer discuss the evolving role of oral estrogen receptor–directed therapies in HR-positive/HER2-negative metastatic breast cancer, with a focus on overcoming endocrine resistance and individualizing treatment. The discussion examines the clinical significance of ESR1 mutations, optimal timing and interpretation of ctDNA testing, and phase III efficacy data from EMERALD, EMBER-3, VERITAC-2, and SERENA-6. Particular attention is given to biomarker-guided treatment selection, including the potential for early therapeutic intervention following detection of emerging ESR1 mutations before clinical disease progression, and sequencing strategies when multiple actionable alterations are present. The experts also address agent-specific safety considerations, adverse event monitoring and management, patient counseling, adherence, and practical barriers to care, emphasizing the importance of balancing treatment efficacy, tolerability, and quality of life.

Released: October 29, 2026

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Provided by

Provided by Clinical Care Options, LLC dba Decera Clinical Education

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Supporters

AstraZeneca

Lilly

Stemline Therapeutics, Inc.

Target Audience

This activity is intended for nurse practitioners, physician associates, clinical nurse specialists, and advanced degree nurses who care for patients with HR-positive/HER2-negative metastatic breast cancer. 

Learning Objectives

Upon completion of this activity, participants should be able to:

  • Assess for ESR1 mutations and other actionable genetic alterations in patients with progressive or recurrent ER-positive/HER2-negative MBC consistent with current evidence and local expert guidance

  • Integrate recent evidence for next-generation SERDs into care for patients with endocrine-resistant ER-positive/HER2-negative MBC, considering patient/disease factors, evidence, and local expert guidance

  • Appraise emerging evidence for novel next-generation SERDs and note clinical implications for management of ER-positive/HER2-negative MBC

Additional Disclosures

Generative artificial intelligence (AI) tools were used for data analysis or summarization influencing content and revising or refining educational content. All AI-assisted content underwent human review, editing, and validation by qualified faculty and accredited education staff to ensure scientific accuracy, balance, and compliance with the ACCME Standards for Integrity and Independence in Accredited Continuing Education.