Navigating Complexity in the Post-CDK4/6 Inhibitor Treatment Setting for Patients With ER+/HER2- mBC: Strategies for Optimally Integrating Next-Generation Oral SERDs

The management of hormone receptor–positive (HR-positive), human epidermal growth factor receptor 2–negative (HER2-negative) metastatic breast cancer (mBC) is undergoing rapid transformation, largely driven by the imperative to overcome acquired endocrine resistance, frequently mediated by somatic estrogen receptor 1 (ESR1) mutations. These mutations predict a lack of benefit from further aromatase inhibitor (AI) therapy, making the correct identification and subsequent targeting of these alterations critical for guiding treatment selection. Next-generation oral selective estrogen receptor degraders (SERDs) offer improved efficacy and enhanced estrogen receptor (ER)-degrading potential, especially in ESR1-mutated tumors, thus positioning them as crucial options in the post-cyclin-dependent kinase 4/6 (CDK4/6) inhibitor setting. However, data from the 2025 RETRACT survey revealed that next-generation sequencing (NGS) remains underutilized in mBC patients and that significant variability exists in therapeutic decision-making, indicating the need for clear, evidence-informed guidance on post–CDK4/6 inhibitor treatment sequencing.
 
To address these gaps in testing and treatment, and ensure that clinicians can effectively evaluate the mechanisms of action and efficacy data of new and emerging next-generation SERDs, this educational activity utilizes the RE-AIM training and implementation model to 1) facilitate peer-to-peer learning at the point of care around novel and emerging oral SERDs and oral SERD combinations; and 2) build the appropriate infrastructure, clinical capacity, and training in oncology practices to optimally adopt these novel therapies in patients with estrogen receptor-positive/HER2-negative mBC.
 
Educational Partner: Academy for Continued Healthcare Learning (ACHL)
 
Commercial Supporter: Supported by an educational grant from Lilly.

Target Audience

This educational activity is designed for oncologists, oncology NPs/PAs, oncology pharmacists and other members of the multidisciplinary oncology team.

Learning Objectives

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

  • Differentiate the strengths, limitations, and appropriate clinical applications of circulating tumor DNA (ctDNA)–based testing platforms, such as droplet digital polymerase chain reaction (ddPCR) and next-generation sequencing (NGS), to optimize detection and monitoring of estrogen receptor 1 (ESR1) mutations in estrogen receptor–positive (ER-positive)/ human epidermal growth factor receptor 2–negative (HER2-negative) metastatic breast cancer (mBC)
  • Evaluate the mechanisms of action and efficacy data of new and emerging next-generation selective estrogen receptor degraders (SERDs) to support evidence-informed therapeutic decision-making
  • Apply evidence from emerging clinical trials, such as the combination of next-generation oral SERDs with targeted agents, to inform individualized decision-making for patients with ER-positive/HER2-negative mBC in the post-cyclin-dependent kinase 4/6 (CDK4/6) inhibitor setting
  • Implement evidence-based approaches for monitoring, recognizing, and managing adverse events (AEs) associated with oral SERDs and SERD-containing combinations to maintain treatment adherence and optimize patient outcomes.
Additional information
ACGME/ABMS Core Competencies: 
Patient Care and Procedural Skills
Medical Knowledge
Practice-based Learning and Improvement
Systems-based Practice
For more information, please contact:
CME Coordinator Contact Name: 
Nora Eldasher
CME Coordinator Contact Email: 
[email protected]
Summary
Activity opens: 
07/31/2026
Activity expires: 
07/31/2027
FACULTY
Erica L. Mayer, MD, MPH, FASCO (Chair)
Director of Breast Cancer Clinical Research
Dana-Farber Cancer Institute
Associate Professor in Medicine
Harvard Medical School
Boston, MA
 
Nan Chen, MD
Assistant Professor of Medicine
University of Chicago
 
Jodi Taraba, PharmD, MSc, BCOP
Breast Cancer Clinical Pharmacist
Assistant Professor of Pharmacy
Mayo Clinic - Rochester
 
Disclosure Declarations
As a provider accredited by the ACCME, The University of Chicago Pritzker School of Medicine asks everyone in a position to control the content of an education activity to disclose all financial relationships with any ineligible companies. This includes any entity whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients. Financial relationships are relevant if a financial relationship, in any amount, exists between the person in control of content and an ineligible company during the past 24 months, and the content of the education is related to the products of an ineligible company with whom the person has a financial relationship. Mechanisms are in place to identify and mitigate any relevant financial relationships prior to the start of the activity.

Additionally, The University of Chicago Pritzker School of Medicine requires Authors to identify investigational products or off-label uses of products regulated by the US Food and Drug Administration at first mention and where appropriate in the content.
Physician Credit
The University of Chicago Pritzker School of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

The University of Chicago Pritzker School Of Medicine designates this live activity for a maximum of 2 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
 
Physician assistants, nurse practitioners, and nurses may participate in this educational activity and earn a certificate of completion as AAPA, AANP, and ANCC accept AMA PRA Category 1 Credits™ through their reciprocity agreements.
 

Completion of this activity, including the pretest, posttest, and follow-up assessments, qualifies as a medium weight MIPS improvement activity under MACRA and can be claimed as completion of IA_PSPA 28 of an Accredited Safety or Quality Improvement Program in the Quality Payment Program. Clinicians should submit their improvement activities by attestation via the CMS Quality Payment Program website. You will receive additional information after completing the activity and receiving your certificate via email.
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