Overview
Navigating Complexity in the Post-CDK4/6 Inhibitor Treatment Setting for Patients With ER+/HER2- mBC: Strategies for Optimally Integrating Next-Generation Oral SERDs
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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.
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.
This educational activity is designed for oncologists, oncology NPs/PAs, oncology pharmacists and other members of the multidisciplinary oncology team.
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
- Evolving Treatment Landscape in Hormone Receptor–Positive (HR-positive), Human Epidermal Growth Factor Receptor 2–Negative (HER2-negative) Metastatic Breast Cancer (mBC)
- Mechanistic and Clinical Implications of ESR1 Mutations
- Diagnostic Landscape and Testing Challenges for ESR1 Mutations
- Next-Generation Oral SERDs
- Evolving Combination Treatment Strategies
- Addressing Clinical Integration Challenges
Provided by University of Chicago Pritzker School of Medicine and the Academy for Continued Healthcare Learning (ACHL).
Supported by an educational grant from Lilly.
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
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
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.
The following financial relationships have been provided:
Erica L. Mayer, MD, MPH, FASCO - Consultant: AstraZeneca, Novartis, Lilly, Genentech/Roche, Aktis, Puma, Blue EarthNan Chen, MD - Consultant: Daiichi Sankyo, Stemline, Guardant Health, Novartis, Genentech, Olema TherapeuticsJodi Taraba, PharmD, M.Sc., BCOP - Other: Celcuity, Tersera
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.
The following financial relationships have been provided:
Erica L. Mayer, MD, MPH, FASCO - Consultant: AstraZeneca, Novartis, Lilly, Genentech/Roche, Aktis, Puma, Blue EarthNan Chen, MD - Consultant: Daiichi Sankyo, Stemline, Guardant Health, Novartis, Genentech, Olema TherapeuticsJodi Taraba, PharmD, M.Sc., BCOP - Other: Celcuity, Tersera
The University of Chicago Pritzker School of Medicine, ACHL staff members and others involved with the planning, development, and review of the content for this activity have no relevant affiliations or financial relationships to disclose.
All of the relevant financial relationships listed for these individuals have been mitigated.
All of the relevant financial relationships listed for these individuals have been mitigated.
The content for this activity was developed independently of any ineligible company. All materials are included with permission. The opinions expressed are those of the faculty and are not to be construed as those of the publisher or grantor(s).
This educational activity was planned and produced in accordance with the ACCME Standards for Integrity and Independence in Accredited Continuing Education. Recommendations involving clinical medicine in a continuing medical education (CME/CE) activity must be based on evidence that is accepted within the profession of medicine as adequate justification for their indications and contraindications in the care of patients. All scientific research referred to, reported, or used in CME/CE in support or justification of a patient care recommendation must conform to the generally accepted standards of experimental design, data collection, and analysis.
This CME/CE activity might describe the off-label, investigational, or experimental use of medications and/or devices that may exceed their FDA-approved labeling. Physicians should consult the current manufacturers’ prescribing information for these products. ACHL and The University of Chicago require the speaker to disclose that a product is not labeled for the use under discussion.
Discussion of scientific information on unapproved uses (SIUU), off-label, investigational, or experimental drug/device use: Camizestrant, giredestrant, and gedatolisib are not approved for the treatment of metastatic breast cancer. Trastuzumab deruxtecan is not approved from the treatment of HER2-negative breast cancer. Imlunestrant is not approved for use in combination with abemaciclib for the treatment of metastatic breast cancer. Elacestrant is not approved for use in combination with everolimus, alpelisib, abemaciclib, ribociclib, or capivasertib.
This educational activity was planned and produced in accordance with the ACCME Standards for Integrity and Independence in Accredited Continuing Education. Recommendations involving clinical medicine in a continuing medical education (CME/CE) activity must be based on evidence that is accepted within the profession of medicine as adequate justification for their indications and contraindications in the care of patients. All scientific research referred to, reported, or used in CME/CE in support or justification of a patient care recommendation must conform to the generally accepted standards of experimental design, data collection, and analysis.
This CME/CE activity might describe the off-label, investigational, or experimental use of medications and/or devices that may exceed their FDA-approved labeling. Physicians should consult the current manufacturers’ prescribing information for these products. ACHL and The University of Chicago require the speaker to disclose that a product is not labeled for the use under discussion.
Discussion of scientific information on unapproved uses (SIUU), off-label, investigational, or experimental drug/device use: Camizestrant, giredestrant, and gedatolisib are not approved for the treatment of metastatic breast cancer. Trastuzumab deruxtecan is not approved from the treatment of HER2-negative breast cancer. Imlunestrant is not approved for use in combination with abemaciclib for the treatment of metastatic breast cancer. Elacestrant is not approved for use in combination with everolimus, alpelisib, abemaciclib, ribociclib, or capivasertib.
To receive credit, learners are required to complete a baseline assessment; design, develop, and implement an action plan using our automated platform; view online interventions; and return after 30 days to report progress in making system-level changes. A thorough response to the reflection questionnaire on your involvement in the quality improvement activity is also required for meaningful participation. A certificate will be available upon completion of the reflection questionnaire. There is no fee to participate in the activity or for the generation of the certificate.
The Academy for Continued Healthcare Learning is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.
This activity has been approved for 2.0 contact hours.
ACPE Universal Activity Number: 0396-9999-26-006-H99-P
Activity Type: Application
Release Date: July 31, 2026
Expiration Date: July 31, 2029
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 enduring activity for a maximum of 2.0 AMA PRA Category 1 Credit™. 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.
