Activity Overview
The second-line decision in hormone receptor–positive/HER2-negative (HR+/HER2–) metastatic breast cancer (MBC) is increasingly defined by alterations acquired under treatment rather than by the genomic profile obtained at diagnosis. Approved oral selective estrogen receptor degraders (SERDs) for ESR1-mutated disease, PI3K/AKT/mTOR (PAM) pathway inhibitors for tumors harboring PIK3CA, AKT1, or PTEN alterations, and emerging SERD-based combinations have widened the range of options at progression. Translating that landscape into an individualized recommendation depends on repeat molecular testing, the duration of benefit on prior endocrine-based therapy, and patient comorbidities.
In this activity, 3 experts work through 3 patient cases that reflect these decisions in practice. They examine repeat plasma-based genomic profiling at progression and the biomarker-defined options it identifies, treatment selection when ESR1 and PIK3CA alterations are both actionable and comorbidities constrain the choice, and the evidence for oral SERD monotherapy vs combination therapy after early progression on first-line therapy. Throughout, the faculty discusses how to anticipate, monitor, and manage the adverse effects associated with these regimens.
Target Audience
This educational program is primarily directed toward a global audience of medical oncologists, advanced practice providers, nurses, and other health care professionals who are involved in the management of patients with advanced or metastatic breast cancer.
Learning Objectives
Upon successful completion of this activity, you should be better prepared to:
- Assess emerging clinical trial and real-world evidence to gain practical insights into the appropriate use of oral SERD-based strategies for patients with HR+/HER2– MBC
- Apply evidence-based approaches to anticipate, monitor, and manage adverse effects associated with targeted therapies for patients with HR+/HER2– MBC
- Integrate clinical trial data, real-world evidence, and patient- and disease-specific factors to inform personalized treatment decisions for patients with HR+/HER2– MBC
Erica L. Mayer, MD, MPH
Associate Professor, Medicine
Harvard Medical School
Director, Clinical Research
Faulkner Hospital
Dana-Farber Cancer Institute
Boston, MA
Disclosures: Consultant: Aktis Oncology, AstraZeneca Pharmaceuticals LP, Genentech, a member of the Roche Group, Lilly, Novartis
Jason Aboudi Mouabbi, MD
Assistant Professor, Department of Breast Medical Oncology
Division of Cancer Medicine
The University of Texas MD Anderson Cancer Center
Houston, TX
Disclosures: Advisor, Consultant, Speaker, Honoraria Recipient: Agendia, Aptitude Health, AstraZeneca, BostonGene, Community Health Media, GE HealthCare, PreludeDx, Stemline Therapeutics; Grant/Research Funding: Bristol Myers Squibb, Summit Therapeutics
Erika P. Hamilton, MD
Chief Development Officer, Late Phase
Director, Breast Cancer Research
Sarah Cannon Research Institute
Nashville, TN
Disclosures: Consultant (all payments to institution): Accutar Biotechnology, Arvinas, AstraZeneca, BeiGene, Circle Pharma, Daiichi Sankyo, Entos, Gilead Sciences, Halda Therapeutics, Incyclix Bio, IQVIA, Janssen, Jazz Pharmaceuticals, Jefferies LLC, Johnson & Johnson, Lilly, Medical Pharma Services, Mersana, Novartis, Pfizer, Pyxis Oncology, Roche/Genentech, Samsung Bioepis, Shorla Pharma, Stemline Therapeutics, Tempus Labs, Zentalis Pharmaceuticals; Research Funding (all payments to institution): AbbVie, Accutar Biotechnology, Acerta Pharma, ADC Therapeutics, AKESOBIO Australia, Amgen, Aravive, ArQule, Artios, Arvinas, AstraZeneca, AtlasMedx, BeiGene, Black Diamond, Bliss Biopharmaceutical, Boehringer Ingelheim, Bristol Myers Squibb, Cascadian Therapeutics, Clovis, Compugen, Context Therapeutics , Cullinan, Curis, CytomX, Daiichi Sankyo, Dana-Farber Cancer Institute, Dantari, Deciphera, Duality Biologics, eFFECTOR Therapeutics, Eisai, Ellipses Pharma, Elucida Oncology, EMD Serono, Fochon Pharmaceuticals, FUJIFILM, G1 Therapeutics, Gilead Sciences, H3 Biomedicine, Harpoon, Hutchison MediPharma, ImmunoGen, Immunomedics, Incyte, Infinity Pharmaceuticals , Inspirna, InventisBio, Jacobio, Karyopharm, K-Group Beta, Kind Pharmaceuticals , Leap Therapeutics, Lilly, Loxo Oncology, Lycera, MabSpace Biosciences, MacroGenics, MedImmune, Mersana, Merus, Millennium, Molecular Templates, Myriad Genetics, Novartis, NuCana, Olema, OncoMed, Oncothyreon, ORIC Pharmaceuticals, Orinove, Orum Therapeutics, Pfizer, PharmaMar, Pieris Pharmaceuticals , Pionyr Immunotherapeutics, Plexxikon, Prelude Therapeutics, ProfoundBio, Radius Health, Regeneron, Relay Therapeutics, Repertoire Immune Medicines, Rgenix, Roche/ Genentech, Seagen, Sermonix Pharmaceuticals, Shattuck Labs, Silverback Therapeutics, Stemcentrx, Stemline Therapeutics, Sutro, Syndax, Syros, Taiho, TapImmune, TESARO, Tolmar, Torque Therapeutics, Treadwell Therapeutics, Verastem, Zenith Epigenetics, Zymeworks
The staff of Physicians’ Education Resource®, LLC have no relevant financial relationships with ineligible companies.
PER® mitigated all conflicts of interest for faculty, staff, and planners before the start of this activity by using a multistep process.
Off-Label Disclosure and Disclaimer
This accredited continuing education activity was planned in accordance with the ACCME Standards for Integrity and Independence to ensure balance, objectivity, independence, and scientific rigor. Faculty were instructed to use generic names when possible and to base recommendations on the best available evidence. Proprietary product names may be referenced in clinical discussion for educational purposes only and do not imply endorsement.
This activity may include discussion of investigational, unapproved, or off‑label uses of drugs or devices. Learners are advised to consult prescribing information for products discussed. Content is provided for educational purposes only and is not a substitute for the independent clinical judgment of a health care professional. Learners are encouraged to critically evaluate the information presented and apply their own clinical judgment.
The views expressed are those of the individual faculty members and do not necessarily reflect the views of the accredited provider or any entity providing commercial support.
This activity may have used AI-assisted tools to support educational development. All content was reviewed and approved by qualified faculty or planners. The accredited provider retains full responsibility for accuracy, balance, and independence.