Faculty

TARGET AUDIENCE
This program is intended for medical oncologists, breast surgeons, radiation oncologists and other healthcare professionals involved in the diagnosis and treatment of breast cancer.

LEARNING OBJECTIVES

• Assess available Phase III data with HER2-directed antibody-drug conjugate (ADC) therapy as a component of neoadjuvant therapy for patients with high-risk localized breast cancer, and consider the potential clinical role of this novel treatment approach.
• Evaluate available research findings with HER2-directed ADC therapy for patients with HER2-positive localized breast cancer and residual disease after neoadjuvant treatment.
• Appraise available research data and clinical and biological factors guiding the selection of first-line therapy for patients with newly diagnosed HER2-positive metastatic breast cancer (mBC).
• Review published research supporting the use of TROP2-directed ADCs as monotherapy or in combination with anti-PD-1/PD-L1 antibodies for patients with newly diagnosed triple-negative mBC, and use this information to make appropriate treatment recommendations.
• Evaluate published clinical research findings with TROP2-directed ADCs for relapsed/refractory HR-positive and triple-negative mBC, and optimally incorporate these agents into patient care.
• Assess the biological rationale for the evaluation of HER2-directed ADCs for HER2-low and HER2-ultralow mBC, and identify patients appropriate for this treatment approach.
• Discern the side effects and toxicities associated with FDA-approved ADCs in the care of patients with breast cancer, and identify strategies to manage and mitigate those complications.
• Recall ongoing trials evaluating the potential role of novel ADC-based strategies, and appropriately counsel patients with breast cancer regarding enrollment.

ACCREDITATION STATEMENT
Research To Practice is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

CREDIT DESIGNATION STATEMENT
Research To Practice designates this enduring material for a maximum of 1.5 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

AMERICAN BOARD OF INTERNAL MEDICINE (ABIM) — MAINTENANCE OF CERTIFICATION (MOC)
Successful completion of this CME activity, which includes participation in the evaluation component and a post-test, enables the participant to earn up to 1.5 Medical Knowledge MOC points in the American Board of Internal Medicine’s (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit.

Please note, these programs have been specifically designed for the following ABIM specialty: medical oncology.

AMERICAN BOARD OF SURGERY (ABS) — CONTINUOUS CERTIFICATION (CC)
Successful completion of these CME activities, which includes participation in the evaluation component and post-tests, enables the learner to earn credit toward the CME and Self-Assessment requirement(s) of the American Board of Surgery’s Continuous Certification program. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABS credit.

Please note, these programs have been specifically designed for the following ABS practice area: complex general surgical oncology.

PRIVACY POLICY
Personal information and data sharing: Research To Practice aggregates deidentified user data for program-use analysis, program development, activity planning and site improvement. We may provide aggregate and deidentified data to third parties, including commercial supporters. We do not share or sell personally identifiable information to any unaffiliated third parties or commercial supporters. Please see our privacy policy at ResearchToPractice.com/Privacy-Policy for more information.

HOW TO USE THIS CME ACTIVITY
This CME activity consists of a video component. To receive credit, the participant should review the CME information, watch the video, complete the post-test with a score of 80% or better and fill out the evaluation located at ResearchToPractice.com/YIR2025/ADCBreast/Presentations/CME.

CONTENT VALIDATION AND DISCLOSURES
Research To Practice (RTP) is committed to providing its participants with high-quality, unbiased and state-of-the-art education and adheres to the ACCME’s Standards for Integrity and Independence in Accredited Continuing Education. Any individuals in a position to control the content of an accredited continuing education activity, including faculty, planners, reviewers and others, are required to disclose all relevant financial relationships with ineligible entities (commercial interests). All relevant financial relationships have been mitigated prior to the commencement of this activity. In addition, all activity content is reviewed by RTP scientific staff and an external, independent physician reviewer for fair balance, scientific objectivity of studies referenced and patient care recommendations.

FACULTY — The following faculty reported relevant financial relationships with ineligible entities:

Hope S Rugo, MD
Director, Women’s Cancers Program
Division Chief, Breast Medical Oncology
Professor, Department of Medical Oncology
and Therapeutics Research
City of Hope Comprehensive Cancer Center
Duarte, California
Professor Emeritus, UCSF

Advisory Committees and Consulting Agreements: BioNTech SE, Bristol Myers Squibb, Helsinn Therapeutics (US) Inc, Napo Pharmaceuticals; Contracted Research (Funding to City of Hope): Bicycle Therapeutics, Genentech, a member of the Roche Group, Stemline Therapeutics Inc; Contracted Research (Funding to Prior Institution, UCSF): Ambrx Inc, AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, Genentech, a member of the Roche Group, Gilead Sciences Inc, Lilly, Merck, Novartis, Pfizer Inc, Stemline Therapeutics Inc.

Sara M Tolaney, MD, MPH
Chief, Division of Breast Oncology
Dana-Farber Cancer Institute
Associate Professor of Medicine
Harvard Medical School
Boston, Massachusetts

Consulting Agreements: Aadi Bioscience, Aktis Oncology, Ambrx, Artios Pharma Limited, Arvinas, AstraZeneca Pharmaceuticals LP, Avenzo Therapeutics, Bayer HealthCare Pharmaceuticals, BeOne, Bicycle Therapeutics, BioNTech SE, Blueprint Medicines, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, Celcuity, Circle Pharma, Cullinan Therapeutics, Daiichi Sankyo Inc, eFFECTOR Therapeutics Inc, Eisai Inc, Genentech, a member of the Roche Group, Gilead Sciences Inc, Hengrui Therapeutics Inc, Jazz Pharmaceuticals Inc, Johnson & Johnson, Launch Therapeutics, Lilly, Menarini Group, Merck, Mersana Therapeutics Inc, Natera Inc, Olema Oncology, Pfizer Inc, Reveal Genomics, Samsung Bioepis, Seagen Inc, Stemline Therapeutics Inc, Sumitovant Biopharma, Summit Therapeutics, SystImmune Inc, Tango Therapeutics, Tempus, Zuellig Pharma; Contracted Research: AstraZeneca Pharmaceuticals LP, Bristol Myers Squibb, Daiichi Sankyo Inc, Exelixis Inc, Genentech, a member of the Roche Group, Gilead Sciences Inc, Jazz Pharmaceuticals Inc, Lilly, Menarini Group, Merck, NanoString Technologies, Novartis, OncoPep, Pfizer Inc, Seagen Inc, Stemline Therapeutics Inc; Travel Support: Arvinas, AstraZeneca Pharmaceuticals LP, Gilead Sciences Inc, Jazz Pharmaceuticals Inc, Lilly, Pfizer Inc, Roche Laboratories Inc.

MODERATOR — Dr Love is president and CEO of Research To Practice. Research To Practice receives funds in the form of educational grants to develop CME activities from the following companies: Aadi Bioscience, AbbVie Inc, ADC Therapeutics, Agendia Inc, Alexion Pharmaceuticals, Amgen Inc, Array BioPharma Inc, a subsidiary of Pfizer Inc, Arvinas, Astellas, AstraZeneca Pharmaceuticals LP, Aveo Pharmaceuticals, Bayer HealthCare Pharmaceuticals, BeOne, Biotheranostics Inc, A Hologic Company, Black Diamond Therapeutics Inc, Blueprint Medicines, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, Celcuity, Clovis Oncology, Coherus BioSciences, Corcept Therapeutics Inc, CTI BioPharma, a Sobi Company, Daiichi Sankyo Inc, Eisai Inc, Elevation Oncology Inc, Exact Sciences Corporation, Exelixis Inc, Genentech, a member of the Roche Group, Genmab US Inc, Geron Corporation, Gilead Sciences Inc, GSK, Helsinn Therapeutics (US) Inc, ImmunoGen Inc, Incyte Corporation, Ipsen Biopharmaceuticals Inc, Jazz Pharmaceuticals Inc, Johnson & Johnson, Karyopharm Therapeutics, Kite, A Gilead Company, Kura Oncology, Legend Biotech, Lilly, MEI Pharma Inc, Merck, Mersana Therapeutics Inc, Mirati Therapeutics Inc, Mural Oncology Inc, Natera Inc, Novartis, Novartis Pharmaceuticals Corporation on behalf of Advanced Accelerator Applications, Novocure Inc, Nuvalent, Nuvation Bio Inc, Pfizer Inc, Pharmacyclics LLC, an AbbVie Company, Puma Biotechnology Inc, Regeneron Pharmaceuticals Inc, Revolution Medicines Inc, Rigel Pharmaceuticals Inc, R-Pharm US, Sanofi, Seagen Inc, Servier Pharmaceuticals LLC, SpringWorks Therapeutics Inc, Stemline Therapeutics Inc, Sumitomo Pharma America, Syndax Pharmaceuticals, Taiho Oncology Inc, Takeda Pharmaceuticals USA Inc, TerSera Therapeutics LLC, and Tesaro, A GSK Company.

RESEARCH TO PRACTICE CME PLANNING COMMITTEE MEMBERS, STAFF AND REVIEWERS — Planners, scientific staff and independent reviewers for Research To Practice have no relevant financial relationships to disclose.

These educational activities contain discussion of published and/or investigational uses of agents that are not indicated by the Food and Drug Administration. Research To Practice does not recommend the use of any agent outside of the labeled indications. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications and warnings. The opinions expressed are those of the presenters and are not to be construed as those of the publisher or grantors.

These activities are supported by educational grants from AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, and Gilead Sciences Inc.

Release date: March 2026
Expiration date: March 2027

After completing the post-test, learners may download and review the answers here in order to identify further areas of study.

Bardia A et al. Datopotamab deruxtecan versus chemotherapy in previously treated inoperable/metastatic hormone receptor-positive human epidermal growth factor receptor 2-negative breast cancer: Primary results from TROPION-Breast01. J Clin Oncol 2025;43(3):285-96. Abstract

Cortés J et al. Sacituzumab govitecan in untreated, advanced triple-negative breast cancer. N Engl J Med 2025;393(19):1912-25. Abstract

Dent RA et al. First-line (1L) datopotamab deruxtecan (Dato-DXd) vs chemotherapy in patients with locally recurrent inoperable or metastatic triple-negative breast cancer (mTNBC) for whom immunotherapy was not an option: Primary results from the randomised, phase III TROPION-Breast02 trial. ESMO 2025;Abstract LBA21.

Fan Y et al. Sacituzumab tirumotecan (sac-TMT) vs investigator’s choice of chemotherapy (ICC) in previously treated locally advanced or metastatic hormone receptor-positive, HER2-negative (HR+/HER2-) breast cancer (BC): Results from the randomized, multi-center phase III OptiTROP-Breast02 study. ESMO 2025;Abstract LBA23.

Harbeck N et al. Neoadjuvant trastuzumab deruxtecan alone or followed by paclitaxel, trastuzumab, and pertuzumab for high-risk HER2-positive early breast cancer (DESTINY-Breast11): A randomised, open-label, multicentre, phase III trial. Ann Oncol 2026;37(2):166-79. Abstract

Hu X et al. Patient-reported outcomes with trastuzumab deruxtecan in hormone receptor-positive, HER2-low or HER2-ultralow metastatic breast cancer: Results from the randomized DESTINY-Breast06 trial. ESMO Open 2025;10(5):105082. Abstract

Hu X et al. Trastuzumab botidotin vs trastuzumab emtansine (T-DM1) in HER2-positive unresectable or metastatic breast cancer: Results from a randomized phase III study. ESMO 2025;Abstract LBA24.

Jhaveri KL et al. Sacituzumab govitecan vs chemotherapy as first therapy after endocrine therapy in HR+/HER2− (IHC 0, 1+, 2+/ISH−) metastatic breast cancer: Primary results from ASCENT-07. San Antonio Breast Cancer Symposium 2025;Abstract GS1-09.

Loibl S et al. Trastuzumab deruxtecan in residual HER2-positive early breast cancer. N Engl J Med 2025;[Online ahead of print]. Abstract

Modi S et al. Trastuzumab deruxtecan in HER2-low metastatic breast cancer: Long-term survival analysis of the randomized, phase 3 DESTINY-Breast04 trial. Nat Med 2025;31(12):4205-13. Abstract

Natsuhara KH et al. Treatment rechallenge after trastuzumab-deruxtecan–related interstitial lung disease: A multi-institution cohort study. ASCO 2025;Abstract 1015.

Pistilli B et al. Datopotamab deruxtecan (Dato-DXd) vs chemotherapy (CT) in previously-treated inoperable or metastatic hormone receptor-positive, HER2-negative (HR+/HER2–) breast cancer (BC): Final overall survival (OS) from the phase III TROPION-Breast01 trial. ESMO Virtual Plenary 2025;Abstract VP1-2025.

Rugo HS et al. Q-TWiST analysis of sacituzumab govitecan vs chemotherapy in previously treated patients with HR+/HER2- metastatic breast cancer. Curr Oncol 2025;32(3):169. Abstract

Sakai H et al. A randomized, double-blind, placebo-controlled phase II study of olanzapine-based prophylactic antiemetic therapy for delayed and persistent nausea and vomiting in patients with HER2-positive or HER2-low breast cancer treated with trastuzumab deruxtecan: ERICA study (WJOG14320B). Ann Oncol 2025;36(1):31-42. Abstract

Song E et al. SHR-A1811 versus pyrotinib plus capecitabine in human epidermal growth factor receptor 2-positive (HER2+) advanced/metastatic breast cancer (BC): A multicenter, open-label, randomized, phase III study (HORIZON-Breast01). ESMO 2025;Abstract LBA19.

Tolaney SM et al. Trastuzumab deruxtecan plus pertuzumab for HER2-positive metastatic breast cancer. N Engl J Med 2026;394(6):551-62. Abstract

Tolaney SM et al. Sacituzumab govitecan (SG) + pembrolizumab (pembro) vs chemotherapy (chemo) + pembro in previously untreated PD-L1–positive advanced triple-negative breast cancer (TNBC): Primary results from the randomized phase 3 ASCENT-04/KEYNOTE-D19 study. ASCO 2025;Abstract LBA109.

Wildiers H et al. Outcomes by hormone receptor (HR) status in patients (pts) with HER2+ advanced/metastatic breast cancer (mBC) with brain metastases (BM) treated with trastuzumab deruxtecan (T-DXd): A post-hoc subgroup analysis of DESTINY-Breast12. San Antonio Breast Cancer Symposium 2025;Abstract PS5-01-27.

Yin Y et al. Sacituzumab tirumotecan in previously treated metastatic triple-negative breast cancer: A randomized phase 3 trial. Nat Med 2025;31(6):1969-75. Abstract

Yin Y et al. Sacituzumab tirumotecan (sac-TMT) as first-line treatment for unresectable locally advanced/metastatic triple-negative breast cancer (a/mTNBC): Initial results from the phase II OptiTROP-Breast05 study. ASCO 2025;Abstract 1019.

Faculty

TARGET AUDIENCE
This program is intended for medical oncologists, breast surgeons, radiation oncologists and other healthcare professionals involved in the diagnosis and treatment of breast cancer.

LEARNING OBJECTIVES

• Evaluate available research establishing the utility of various genomic assays in personalizing adjuvant systemic therapy for hormone receptor (HR)-positive, HER2-negative breast cancer, and identify patients for whom testing would be clinically useful.
• Consider available clinical trial findings with CDK4/6 inhibitors for localized HR-positive, HER2-negative breast cancer, and identify patients for whom adjuvant treatment with one of these agents may be appropriate.
• Review available research documenting the correlation between the presence of various biomarkers (eg, PIK3CA/AKT1/PTEN alterations, ESR1 mutations) and response to specific therapies, and develop optimal testing algorithms for patients with HR-positive metastatic breast cancer (mBC).
• Appraise published efficacy and safety data from randomized clinical trials evaluating CDK4/6 inhibitors for patients with HR-positive mBC to appropriately counsel patients regarding the optimal use of these agents.
• Interrogate published research documenting the efficacy of oral selective estrogen receptor degraders for HR-positive, HER2-negative mBC progressing on endocrine therapy in combination with a CDK4/6 inhibitor in order to optimally integrate these agents into the care of appropriately selected patients.
• Recognize the frequency of PIK3CA/AKT1/PTEN abnormalities in HR-positive mBC, and employ evidence-based approaches designed to target these aberrations for patients with newly diagnosed and relapsed/refractory disease.
• Consider the spectrum, frequency and severity of adverse events associated with various endocrine-based treatment approaches for HR-positive breast cancer, and appreciate strategies to prevent, ameliorate and manage these side effects.
• Recall the design of ongoing clinical trials evaluating novel endocrine-based strategies for HR-positive breast cancer, and appropriately counsel patients about availability and participation.

ACCREDITATION STATEMENT
Research To Practice is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

CREDIT DESIGNATION STATEMENT
Video Program: Research To Practice designates this enduring material for a maximum of 2.25 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

AMERICAN BOARD OF INTERNAL MEDICINE (ABIM) — MAINTENANCE OF CERTIFICATION (MOC)
Successful completion of these CME activities, which includes participation in the evaluation components and post-tests, enables the participant to earn up to 2.25 (video) Medical Knowledge MOC points in the American Board of Internal Medicine’s (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for each activity. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit.

Please note, these programs have been specifically designed for the following ABIM specialty: medical oncology.

AMERICAN BOARD OF SURGERY (ABS) — CONTINUOUS CERTIFICATION (CC)
Successful completion of these CME activities, which includes participation in the evaluation components and post-tests, enables the learner to earn credit toward the CME and Self-Assessment requirement(s) of the American Board of Surgery’s Continuous Certification program. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABS credit.

Please note, these programs have been specifically designed for the following ABS practice area: complex general surgical oncology.

PRIVACY POLICY
Personal information and data sharing: Research To Practice aggregates deidentified user data for program-use analysis, program development, activity planning and site improvement. We may provide aggregate and deidentified data to third parties, including commercial supporters. We do not share or sell personally identifiable information to any unaffiliated third parties or commercial supporters. Please see our privacy policy at ResearchToPractice.com/Privacy-Policy for more information.

HOW TO USE THIS CME ACTIVITY
This CME activity consists of a video component. To receive credit, the participant should review the CME information, watch the video, complete the post-test with a score of 80% or better and fill out the evaluation located at ResearchToPractice.com/SanAntonioHRPosBC25/Video/CME.

CONTENT VALIDATION AND DISCLOSURES
Research To Practice (RTP) is committed to providing its participants with high-quality, unbiased and state-of-the-art education and adheres to the ACCME’s Standards for Integrity and Independence in Accredited Continuing Education. Any individuals in a position to control the content of an accredited continuing education activity, including faculty, planners, reviewers and others, are required to disclose all relevant financial relationships with ineligible entities (commercial interests). All relevant financial relationships have been mitigated prior to the commencement of this activity. In addition, all activity content is reviewed by RTP scientific staff and an external, independent physician reviewer for fair balance, scientific objectivity of studies referenced and patient care recommendations.

FACULTY — The following faculty reported relevant financial relationships with ineligible entities:

Angela DeMichele, MD, MSCE
Mariann T and Robert J MacDonald Professor in Breast Cancer
Director, Clinical/Translational Research, Solid Tumor Oncology, Hematology/Oncology Division
Co-Leader, Breast Cancer Program
Abramson Cancer Center
Co-Director, 2-PREVENT Breast Cancer Translational Center of Excellence
Senior Scholar, Center for Clinical Epidemiology and Biostatistics
Perelman School of Medicine
University of Pennsylvania
Philadelphia, Pennsylvania

Consulting Agreements: Pfizer Inc; Contracted Research: Genentech, a member of the Roche Group, NeoGenomics, Novartis, Pfizer Inc.

Komal Jhaveri, MD, FACP, FASCO
Patricia and James Cayne Chair for Junior Faculty
Associate Attending Physician
Breast Medicine Service and Early Drug Development Service
Section Head, Endocrine Therapy Research Program
Clinical Director, Early Drug Development Service
Department of Medicine
Memorial Sloan Kettering Cancer Center
Associate Professor of Medicine
Weill Cornell College of Medicine
New York, New York

Consultant/Advisory Board Roles: Arvinas, AstraZeneca Pharmaceuticals LP, Bicycle Therapeutics, Blueprint Medicines, Daiichi Sankyo Inc, Eisai Inc, Genentech, a member of the Roche Group, Gilead Sciences Inc, Halda Therapeutics, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company, Menarini Group, Merck, Novartis, Olema Oncology, Pfizer Inc, RayzeBio Inc, Scorpion Therapeutics, Stemline Therapeutics Inc, Zymeworks Inc; Research Funding Support to the Institution: AstraZeneca Pharmaceuticals LP, Blueprint Medicines, Eisai Inc, Genentech, a member of the Roche Group, Gilead Sciences Inc, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company, Merck, Novartis, Pfizer Inc, Puma Biotechnology Inc, RayzeBio Inc, Scorpion Therapeutics, Zymeworks Inc.

Erica Mayer, MD, MPH, FASCO
Director of Breast Cancer Clinical Research
Breast Oncology Center
Dana-Farber Cancer Institute
Associate Professor of Medicine
Harvard Medical School
Boston, Massachusetts

Consulting Agreements: Aktis Oncology, AstraZeneca Pharmaceuticals LP, Genentech, a member of the Roche Group, Lilly, Novartis.

Hope S Rugo, MD
Director, Women’s Cancers Program
Division Chief, Breast Medical Oncology
Professor, Department of Medical Oncology and Therapeutics Research
City of Hope Comprehensive Cancer Center
Duarte, California
Professor Emeritus, UCSF

Advisory Committees and Consulting Agreements: BioNTech SE, Bristol Myers Squibb, Helsinn Therapeutics (US) Inc, Napo Pharmaceuticals; Contracted Research (Funding to City of Hope): Bicycle Therapeutics, Genentech, a member of the Roche Group, Stemline Therapeutics Inc; Contracted Research (Funding to Prior Institution, UCSF): Ambrx Inc, AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, Genentech, a member of the Roche Group, Gilead Sciences Inc, Lilly, Merck, Novartis, Pfizer Inc, Stemline Therapeutics Inc.

Seth Wander, MD, PhD
Director of Precision Medicine
Termeer Center for Targeted Therapies
Director of Translational Research
Breast Oncology Program
Massachusetts General Hospital
Assistant Professor of Medicine
Harvard Medical School
Boston, Massachusetts

Consulting Agreements: Arvinas, AstraZeneca Pharmaceuticals LP, Biotheranostics Inc, A Hologic Company, Biovica International AB, Foundation Medicine, Genentech, a member of the Roche Group, Gilead Sciences Inc, Lilly, Menarini Group, Novartis, Pfizer Inc, Puma Biotechnology Inc, Regor Therapeutics, Stemline Therapeutics Inc, Veracyte Inc; Contracted Research: Arvinas, Genentech, a member of the Roche Group, Lilly, Menarini Group, Nuvation Bio Inc, Pfizer Inc, Phoenix Molecular Designs, Puma Biotechnology Inc, Regor Therapeutics, Sermonix Pharmaceuticals, Stemline Therapeutics Inc.

MODERATOR — Dr Love is president and CEO of Research To Practice. Research To Practice receives funds in the form of educational grants to develop CME activities from the following companies: Aadi Bioscience, AbbVie Inc, ADC Therapeutics, Agendia Inc, Alexion Pharmaceuticals, Amgen Inc, Array BioPharma Inc, a subsidiary of Pfizer Inc, Arvinas, Astellas, AstraZeneca Pharmaceuticals LP, Aveo Pharmaceuticals, Bayer HealthCare Pharmaceuticals, BeOne, Biotheranostics Inc, A Hologic Company, Black Diamond Therapeutics Inc, Blueprint Medicines, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, Celcuity, Clovis Oncology, Coherus BioSciences, Corcept Therapeutics Inc, CTI BioPharma, a Sobi Company, Daiichi Sankyo Inc, Eisai Inc, Elevation Oncology Inc, Exact Sciences Corporation, Exelixis Inc, Genentech, a member of the Roche Group, Genmab US Inc, Geron Corporation, Gilead Sciences Inc, GSK, Helsinn Therapeutics (US) Inc, ImmunoGen Inc, Incyte Corporation, Ipsen Biopharmaceuticals Inc, Jazz Pharmaceuticals Inc, Johnson & Johnson, Karyopharm Therapeutics, Kite, A Gilead Company, Kura Oncology, Legend Biotech, Lilly, MEI Pharma Inc, Merck, Mersana Therapeutics Inc, Mirati Therapeutics Inc, Mural Oncology Inc, Natera Inc, Novartis, Novartis Pharmaceuticals Corporation on behalf of Advanced Accelerator Applications, Novocure Inc, Nuvalent, Nuvation Bio Inc, Pfizer Inc, Pharmacyclics LLC, an AbbVie Company, Puma Biotechnology Inc, Regeneron Pharmaceuticals Inc, Rigel Pharmaceuticals Inc, R-Pharm US, Sanofi, Seagen Inc, Servier Pharmaceuticals LLC, SpringWorks Therapeutics Inc, Stemline Therapeutics Inc, Sumitomo Pharma America, Syndax Pharmaceuticals, Taiho Oncology Inc, Takeda Pharmaceuticals USA Inc, TerSera Therapeutics LLC, and Tesaro, A GSK Company.

RESEARCH TO PRACTICE CME PLANNING COMMITTEE MEMBERS, STAFF AND REVIEWERS — Planners, scientific staff and independent reviewers for Research To Practice have no relevant financial relationships to disclose.

These educational activities contain discussion of published and/or investigational uses of agents that are not indicated by the Food and Drug Administration. Research To Practice does not recommend the use of any agent outside of the labeled indications. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications and warnings. The opinions expressed are those of the presenters and are not to be construed as those of the publisher or grantors.

These activities are supported by educational grants from Agendia Inc, Biotheranostics Inc, A Hologic Company, Celcuity, Exact Sciences Corporation, Genentech, a member of the Roche Group, Lilly, and Stemline Therapeutics Inc.

Release date: January 2026
Expiration date: January 2027

After completing the post-test, learners may download and review the answers here in order to identify further areas of study.

Dr DeMichele

Andre F et al. Biomarkers for adjuvant endocrine and chemotherapy in early-stage breast cancer: ASCO guideline update. J Clin Oncol 2022;40(16):1816-37. Abstract

Buus R et al. Molecular drivers of Oncotype DX, Prosigna, EndoPredict, and the Breast Cancer Index: A TransATAC study. J Clin Oncol 2021;39(2):126-35. Abstract

Cardoso F et al. 70-gene signature as an aid to treatment decisions in early-stage breast cancer. N Engl J Med 2016;375(8):717-29. Abstract

Chen N et al. Impact of anthracyclines in genomic high-risk, node-negative, HR-positive/HER2-negative breast cancer. Ann Oncol 2025;36(11):1356-65. Abstract

Kalinsky K et al. 21-Gene assay to inform chemotherapy benefit in node-positive breast cancer. N Engl J Med 2021;385(25):2336-47. Abstract

Nguyen B et al. Comparison of molecular subtyping with BluePrint, MammaPrint, and TargetPrint to local clinical subtyping in breast cancer patients. Ann Surg Oncol 2012;19(10):3257-63. Abstract

Pan H et al. 20-year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years. N Engl J Med 2017;377(19):1836-46. Abstract

Piccart M et al. 70-gene signature as an aid for treatment decisions in early breast cancer: Updated results of the phase 3 randomised MINDACT trial with an exploratory analysis by age. Lancet Oncol 2021;22(4):476-88. Abstract

Pusztai L et al. Development and validation of the RSClinN+ tool to predict prognosis and chemotherapy benefit for hormone receptor–positive, node-positive breast cancer. J Clin Oncol 2025;43(8):919-28. Abstract

Sestak I et al. Comparison of the performance of 6 prognostic signatures for estrogen receptor-positive breast cancer: A secondary analysis of a randomized clinical trial. JAMA Oncol 2018;4(4):545-53. Abstract

Sgroi DC et al. Prediction of late disease recurrence and extended adjuvant letrozole benefit by the HOXB13/IL17BR biomarker. J Natl Cancer Inst 2013;105(14):1036-42. Abstract

Sparano JA et al. Trial assigning individualized options for treatment (TAILORx): An update including 12-year event rates. San Antonio Breast Cancer Symposium 2022;Abstract GS1-05.

Sparano JA et al. Development and validation of a tool integrating the 21-gene recurrence score and clinical-pathological features to individualize prognosis and prediction of chemotherapy benefit in early breast cancer. J Clin Oncol 2021;39(6):557-64. Abstract

Sparano JA et al. Clinical outcomes in early breast cancer with a high 21-gene recurrence score of 26 to 100 assigned to adjuvant chemotherapy plus endocrine therapy: A secondary analysis of the TAILORx randomized clinical trial. JAMA Oncol 2020;6(3):367-74. Abstract

Woolpert KM et al. Biomarkers predictive of a response to extended endocrine therapy in breast cancer: A systematic review and meta-analysis. Breast Cancer Res Treat 2024;203(3):407-17. Abstract

Dr Jhaveri

Barrios CH et al. NATALEE update: Safety and treatment (tx) duration of ribociclib (RIB) + nonsteroidal aromatase inhibitor (NSAI) in patients (pts) with HR+/HER2− early breast cancer (EBC). ESMO Breast 2024;Abstract 113MO.

Cortes J et al. monarchE: Subgroup analysis of adjuvant abemaciclib + endocrine therapy for HR+, HER2-, high-risk early breast cancer by nodal status. San Antonio Breast Cancer Symposium 2025;Abstract PS1-08-08.

Crown J et al. Adjuvant ribociclib plus nonsteroidal aromatase inhibitor therapy in patients with HR-positive/HER2-negative early breast cancer: 5-year follow-up of NATALEE efficacy outcomes and updated overall survival. ESMO Open. 2025;10(11). Abstract

Fasching PA et al. Health-related quality of life (HRQoL) in the phase III NATALEE study of adjuvant ribociclib (RIB) plus a nonsteroidal aromatase inhibitor (NSAI) vs NSAI alone in patients (pts) with HR+/HER2− early breast cancer (EBC). ESMO Virtual Plenary 2023;Abstract VP3-2023.

Hamilton EP et al. Efficacy and safety results by age in monarchE: Adjuvant abemaciclib combined with endocrine therapy (ET) in patients with HR+, HER2-, node-positive, high-risk early breast cancer (EBC). ASCO 2023;Abstract 501.

Harbeck N et al. Adjuvant abemaciclib plus endocrine therapy for HR+, HER2-, high-risk early breast cancer: Results from a preplanned monarchE overall survival interim analysis, including 5-year efficacy outcomes. ESMO 2023;Abstract LBA17.

Hortobagyi G et al. Ribociclib (RIB) + nonsteroidal aromatase inhibitor (NSAI) as adjuvant treatment in patients with HR+/HER2− early breast cancer: Final invasive disease–free survival (iDFS) analysis from the NATALEE trial. San Antonio Breast Cancer Symposium 2023;Abstract GS03-03.

Hurvitz S et al. Five-year analysis of distant disease-free survival (DDFS) across key subgroups from the phase 3 NATALEE trial of ribociclib (RIB) plus a nonsteroidal aromatase inhibitor (NSAI) in patients with HR+/HER2− early breast cancer (EBC). San Antonio Breast Cancer Symposium 2025;Abstract PS3-09-08.

Jhaveri K et al. Real-world evidence on risk of recurrence (ROR) in patients (pts) with node-negative (N0) and node-positive HR+/HER2– early breast cancer (EBC) from US electronic health records (EHR). ESMO 2024;Abstract 292P.

Johnston SRD et al. monarchE: Primary overall survival (OS) results of adjuvant abemaciclib + endocrine therapy (ET) for HR+, HER2-, high-risk early breast cancer (EBC). ESMO 2025;Abstract LBA13.

Johnston S et al. Overall survival with abemaciclib in early breast cancer. Ann Oncol 2025;[Online ahead of print]. Abstract

Mayer EL et al. Palbociclib with adjuvant endocrine therapy in early breast cancer: 5-year follow-up analysis of the global multicenter, open-label, randomized phase III PALLAS trial (ABCSG-42/AFT-05/PrE0109/BIG-14-13). Ann Oncol 2025;[Online ahead of print]. Abstract

O’Shaughnessy J et al. Real-world risk of recurrence and treatment outcomes with adjuvant endocrine therapy in patients with stage II-III HR+/HER2- early breast cancer. Breast 2025;81. Abstract

Rastogi P et al. Adjuvant abemaciclib plus endocrine therapy for hormone receptor-positive, human epidermal growth factor receptor 2-negative, high-risk early breast cancer: Results from a preplanned monarchE overall survival interim analysis, including 5-year efficacy outcomes. J Clin Oncol 2024;42(9):987-93. Abstract

Rugo HS et al. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: Safety and patient-reported outcomes from the monarchE study. Ann Oncol 2022;33(6):616-27. Abstract

Slamon DJ et al. Ribociclib plus endocrine therapy in early breast cancer. N Engl J Med 2024;390(12):1080-91. Abstract

Slamon DJ et al. Rationale and trial design of NATALEE: A phase III trial of adjuvant ribociclib + endocrine therapy versus endocrine therapy alone in patients with HR+/HER2- early breast cancer. Ther Adv Med Oncol 2023;15. Abstract

Slamon DJ et al. Ribociclib and endocrine therapy as adjuvant treatment in patients with HR+/HER2- early breast cancer: Primary results from the phase III NATALEE trial. ASCO 2023;Abstract LBA500.

Tolaney SM et al. Real-world risk of recurrence by nodal status in patients with HR+, HER2-, node-positive, high-risk early breast cancer. NCODA 2025;Abstract.

Tolaney SM et al. Long-term patient-reported outcomes from monarchE: Abemaciclib plus endocrine therapy as adjuvant therapy for HR+, HER2-, node-positive, high-risk, early breast cancer. Eur J Cancer 2024;199. Abstract

Dr Rugo

Bidard FC et al. First-line camizestrant for emerging ESR1-mutated advanced breast cancer. N Engl J Med 2025;393(6):569-80. Abstract

Bidard FC et al. Updated results and an exploratory analysis of ESR1m circulating tumor DNA (ctDNA) dynamics from SERENA-6, a phase 3 trial of camizestrant (CAMI) + CDK4/6 inhibitor (CDK4/6i) for emergent ESR1 mutations (ESR1m) during first-line (1L) endocrine-based therapy and ahead of disease progression in patients (pts) with HR+/HER2- advanced breast cancer (ABC). San Antonio Breast Cancer Symposium 2025; Abstract RF7-03

de la Haba-Rodriguez J et al. ABIGAIL: Randomized phase II study of abemaciclib plus endocrine therapy (ET) with or without a short course of induction paclitaxel in patients (pts) with previously untreated HR-positive/HER2-negative advanced breast cancer (HR+/HER2- ABC) with aggressive disease criteria. ESMO 2024;Abstract LBA23.

Dieras V et al. Primary results of Ambre, a randomized phase 3 comparing mono-chemotherapy (ct) vs abemaciclib + endocrine therapy (et) in hr+/her2- advanced breast cancer (abc) with high visceral tumor burden. San Antonio Breast Cancer Symposium 2025;Abstract RF7-06.

Goetz MP et al. Abemaciclib plus a nonsteroidal aromatase inhibitor as initial therapy for HR+, HER2- advanced breast cancer: Final overall survival results of MONARCH 3. Ann Oncol 2024;35(8):718-27. Abstract

Hortobagyi GN et al. Overall survival with ribociclib plus letrozole in advanced breast cancer. N Engl J Med 2022;386(10):942-50. Abstract

Jhaveri KL et al. Overall survival with inavolisib in PIK3CA-mutated advanced breast cancer. N Engl J Med 2025;393(2):151-61. Abstract

Loibl S et al. Primary results of the randomised phase III trial comparing first-line ET plus palbociclib vs standard mono-chemotherapy in women with high risk HER2-/HR+ metastatic breast cancer and indication for chemotherapy – PADMA study. San Antonio Breast Cancer Symposium 2024;Abstract LB1-03.

Lu Y-S et al. Final results of RIGHT Choice: Ribociclib plus endocrine therapy versus combination chemotherapy in premenopausal women with clinically aggressive hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer. J Clin Oncol 2024;42(23):2812-21. Abstract

Mayer E et al. Patient-reported outcomes (PROs) from the SERENA-6 trial of camizestrant (CAMI) + CDK4/6 inhibitor (CDK4/6i) for emergent ESR1m during first-line (1L) endocrine-based therapy and ahead of disease progression in patients (pts) with HR+/HER2– advanced breast cancer (ABC). ESMO 2025;Abstract 486MO.

Rugo HS et al. Comparative overall survival of CDK4/6 inhibitors plus an aromatase inhibitor in HR+/HER2− metastatic breast cancer in the US real-world setting. ESMO Open 2025;10(1). Abstract

Slamon DJ et al. Overall survival with palbociclib plus letrozole in advanced breast cancer. J Clin Oncol 2024;42(9):994-1000. Abstract

Turner NC et al. Camizestrant + CDK4/6 inhibitor (CDK4/6i) for the treatment of emergent ESR1 mutations during first-line (1L) endocrine-based therapy (ET) and ahead of disease progression in patients (pts) with HR+/HER2– advanced breast cancer (ABC): Phase 3, double-blind ctDNA-guided SERENA-6 trial. ASCO 2025;Abstract LBA4.

Turner NC et al. INAVO120: Phase III trial final overall survival (OS) analysis of first-line inavolisib (INAVO)/placebo (PBO) + palbociclib (PALBO) + fulvestrant (FULV) in patients (pts) with PIK3CA-mutated, hormone receptor-positive (HR+), HER2-negative (HER2–), endocrine-resistant advanced breast cancer (aBC). ASCO 2025;Abstract 1003.

Turner NC et al. Inavolisib-based therapy in PIK3CA-mutated advanced breast cancer. N Engl J Med 2024;391(17):1584-96. Abstract

Dr Mayer

Hurvitz SA et al. Gedatolisib (geda) + fulvestrant ± palbociclib (palbo) vs fulvestrant in patients (pts) with HR+/ HER2-/PIK3CA wild-type (WT) advanced breast cancer (ABC): First results from VIKTORIA-1. ESMO 2025;Abstract LBA17.

Rosetti S et al. Gedatolisib shows superior potency and efficacy versus single-node PI3K/AKT/mTOR inhibitors in breast cancer models. NPJ Breast Cancer 2024;10(1):40. Abstract

Turner NC et al. Capivasertib in hormone receptor-positive advanced breast cancer. N Engl J Med 2023;388(22):2058-70. Abstract

Turner NC et al. Circulating tumour DNA analysis to direct therapy in advanced breast cancer (plasmaMATCH): A multicentre, multicohort, phase 2a, platform trial. Lancet Oncol 2020;21(10):1296-308. Abstract

Dr Wander

Bardia A et al. Elacestrant in ER+, HER2- metastatic breast cancer with ESR1-mutated tumors: Subgroup analyses from the phase III EMERALD trial by prior duration of endocrine therapy plus CDK4/6 inhibitor and in clinical subgroups. Clin Cancer Res 2024;30(19):4299-409. Abstract

Bidard F-C et al. Elacestrant (oral selective estrogen receptor degrader) versus standard endocrine therapy for estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: Results from the randomized phase III EMERALD trial. J Clin Oncol 2022;40(28):3246-56. Abstract

Brett JO et al. ESR1 mutation as an emerging clinical biomarker in metastatic hormone receptor-positive breast cancer. Breast Cancer Res 2021;23(1):85. Abstract

Jeselsohn R et al. ESR1 mutations—A mechanism for acquired endocrine resistance in breast cancer. Nat Rev Clin Oncol 2015;12(10):573-83. Abstract

Jhaveri KL et al. Imlunestrant with or without abemaciclib in advanced breast cancer. N Engl J Med 2025;392(12):1189-202. Abstract

Lloyd MR et al. Clinical and genomic factors associated with elacestrant outcomes in ESR1-mutant metastatic breast cancer. Clin Cancer Res 2025;[Online ahead of print]. Abstract

Mayer E et al. Giredestrant (GIRE), an oral selective oestrogen receptor (ER) antagonist and degrader, + everolimus (E) in patients (pts) with ER-positive, HER2-negative advanced breast cancer (ER+, HER2– aBC) previously treated with a CDK4/6 inhibitor (i): Primary results of the phase III evERA BC trial. ESMO 2025;Abstract LBA16.

Rugo HS et al. Real-world outcomes of elacestrant in ER+, HER2−, ESR1-mutant metastatic breast cancer. Clin Cancer Res 2025;[Online ahead of print]. Abstract

Teysir J et al. After a CDK4/6 inhibitor: State of the art in hormone receptor–positive metastatic breast cancer. Am Soc Clin Oncol Educ Book 2025;45(3):e473372. Abstract

Turner NC et al. Circulating tumour DNA analysis to direct therapy in advanced breast cancer (plasmaMATCH): A multicentre, multicohort, phase 2a, platform trial. Lancet Oncol 2020;21(10):1296-308. Abstract

Urso L et al. ESR1 gene mutation in hormone receptor-positive HER2-negative metastatic breast cancer patients: Concordance between tumor tissue and circulating tumor DNA analysis. Front Oncol 2021;11. Abstract

Vasan N et al. Concordance between tissue (tumor DNA) and liquid (ctDNA) biopsy next-generation sequencing (NGS) data in detection of PIK3CA, AKT1, and PTEN alterations in breast cancer: A retrospective analysis. ASCO 2024;Abstract e153033.

Faculty

TARGET AUDIENCE
This activity is intended for medical oncologists, hematology-oncology fellows and other healthcare providers involved in the treatment of breast cancer.

LEARNING OBJECTIVES

• Appreciate the incidence and clinical implications of ESR1 mutations in endocrine-resistant metastatic breast cancer, and determine optimal strategies to effectively identify patients harboring these abnormalities.
• Understand the biological rationale for, mechanism of action of and pharmacologic similarities and differences among available and investigational oral selective estrogen receptor degraders (SERDs).
• Interrogate published research documenting the efficacy of available and investigational oral SERDs for ESR1-mutated ER-positive, HER2-negative metastatic breast cancer progressing on standard endocrine therapy with a CDK4/6 inhibitor in order to optimally integrate these agents into patient care.
• Evaluate available clinical trial data with oral SERDs in combination with other therapeutic agents for patients with and without ESR1 mutations, and consider the potential role of these regimens.
• Appreciate the side effects associated with available and investigational oral SERDs, and use this information to develop supportive management plans for patients undergoing treatment with this form of therapy.
• Assess ongoing clinical research evaluating novel applications of oral SERDs for ER-positive breast cancer, and counsel patients regarding the potential benefits of trial participation.

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Video Interview: Research To Practice designates this enduring material for a maximum of 2.75 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

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Successful completion of these CME activities, which includes participation in the evaluation components and post-tests, enables the participant to earn up to 2.75 (video) Medical Knowledge MOC points in the American Board of Internal Medicine’s (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for each activity. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit.

Please note, these programs have been specifically designed for the following ABIM specialty: medical oncology.

AMERICAN BOARD OF SURGERY (ABS) — CONTINUOUS CERTIFICATION (CC)
Successful completion of these CME activities, which includes participation in the evaluation components and post-tests, enables the learner to earn credit toward the CME and Self-Assessment requirement(s) of the American Board of Surgery’s Continuous Certification program. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABS credit.

Please note, these programs have been specifically designed for the following ABS practice area: complex general surgical oncology.

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HOW TO USE THIS CME ACTIVITY
This CME activity consists of a video component. To receive credit, the participant should review the CME information, watch the video, complete the post-test with a score of 80% or better and fill out the evaluation located at ResearchToPractice.com/OralSERDsmBCThinkTank2025/Video/CME.

CONTENT VALIDATION AND DISCLOSURES
Research To Practice (RTP) is committed to providing its participants with high-quality, unbiased and state-of-the-art education and adheres to the ACCME’s Standards for Integrity and Independence in Accredited Continuing Education. Any individuals in a position to control the content of an accredited continuing education activity, including faculty, planners, reviewers and others, are required to disclose all relevant financial relationships with ineligible entities (commercial interests). All relevant financial relationships have been mitigated prior to the commencement of this activity. In addition, all activity content is reviewed by RTP scientific staff and an external, independent physician reviewer for fair balance, scientific objectivity of studies referenced and patient care recommendations.

FACULTY — The following faculty reported relevant financial relationships with ineligible entities:

Francois-Clement Bidard, MD, PhD
Professor of Medical Oncology
Institut Curie
Paris, France

Advisory Committees: AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, Foresight Diagnostics, Inatherys, Lilly, Menarini Silicon Biosystems, Novartis, Pfizer Inc, Roche Laboratories Inc, SAGA Diagnostics; Congress Attendance Support: AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, Novartis, Pfizer Inc, Roche Laboratories Inc; Contracted Research: GE Healthcare, Menarini Silicon Biosystems, Merck KGaA, MSD, Novartis, Personalis, Pfizer Inc, ProLynx Inc, Roche Laboratories Inc, SAGA Diagnostics, Tempus; Speakers Bureaus: AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, Lilly, Novartis, Roche Laboratories Inc.

Hope S Rugo, MD
Director, Women’s Cancers Program
Division Chief, Breast Medical Oncology
Professor, Department of Medical Oncology and Therapeutics Research
City of Hope Comprehensive Cancer Center
Duarte, California
Professor Emeritus, UCSF

Advisory Committees: Bristol Myers Squibb, Chugai Pharmaceutical Co Ltd, Napo Pharmaceuticals Inc, Sanofi; Contracted Research (Institutional Research Support): Ambrx, AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, Genentech, a member of the Roche Group, Gilead Sciences Inc, Lilly, Merck, Novartis, OBI Pharma Inc, Pfizer Inc, Stemline Therapeutics Inc.

Rebecca Shatsky, MD
Professor of Clinical Medicine
Breast Medical Oncology Team Leader
Director of Breast Cancer Clinical Trials
Director of Inflammatory and Triple Negative Breast Cancer Program
University of California San Diego
Moores Cancer Center
San Diego, California

Advisory Committees: AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, Gilead Sciences Inc, Lilly, Merck, Novartis, Pfizer Inc, Stemline Therapeutics Inc; Consulting Agreements: Daiichi Sankyo Inc; Contracted Research: Institutional funding (principal investigator for trials) — Alterome Therapeutics, AstraZeneca Pharmaceuticals LP, BriaCell, Gilead Sciences Inc, Hummingbird Bioscience, Jazz Pharmaceuticals Inc, Mabwell Therapeutics Inc, OBI Pharma Inc, OnKure Therapeutics, Regor Therapeutics, Stemline Therapeutics Inc.

Seth Wander, MD, PhD
Director of Precision Medicine
Termeer Center for Targeted Therapies
Director of Translational Research
Breast Oncology Program
Massachusetts General Hospital
Assistant Professor of Medicine
Harvard Medical School
Boston, Massachusetts

Consulting Agreements: Arvinas, AstraZeneca Pharmaceuticals LP, Biovica International AB, Foundation Medicine, Genentech, a member of the Roche Group, Gilead Sciences Inc, Hologic Inc, Lilly, Menarini Group, Novartis, Pfizer Inc, Puma Biotechnology Inc, Regor Therapeutics, Stemline Therapeutics Inc, Veracyte Inc; Contracted Research: Arvinas, Genentech, a member of the Roche Group, Lilly, Menarini Group, Nuvation Bio, Pfizer Inc, Phoenix Molecular Designs, Puma Biotechnology Inc, Regor Therapeutics, Sermonix Pharmaceuticals, Stemline Therapeutics Inc.

EDITOR — Dr Love is president and CEO of Research To Practice. Research To Practice receives funds in the form of educational grants to develop CME activities from the following companies: Aadi Bioscience, AbbVie Inc, ADC Therapeutics, Agendia Inc, Alexion Pharmaceuticals, Amgen Inc, Array BioPharma Inc, a subsidiary of Pfizer Inc, Arvinas, Astellas, AstraZeneca Pharmaceuticals LP, Aveo Pharmaceuticals, Bayer HealthCare Pharmaceuticals, BeOne, Black Diamond Therapeutics Inc, Blueprint Medicines, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, Clovis Oncology, Coherus BioSciences, Corcept Therapeutics Inc, CTI BioPharma, a Sobi Company, Daiichi Sankyo Inc, Eisai Inc, Elevation Oncology Inc, Exact Sciences Corporation, Exelixis Inc, Genentech, a member of the Roche Group, Genmab US Inc, Geron Corporation, Gilead Sciences Inc, GSK, Helsinn Therapeutics (US) Inc, Hologic Inc, ImmunoGen Inc, Incyte Corporation, Ipsen Biopharmaceuticals Inc, Jazz Pharmaceuticals Inc, Johnson & Johnson, Karyopharm Therapeutics, Kite, A Gilead Company, Kura Oncology, Legend Biotech, Lilly, MEI Pharma Inc, Merck, Mersana Therapeutics Inc, Mirati Therapeutics Inc, Mural Oncology Inc, Natera Inc, Novartis, Novartis Pharmaceuticals Corporation on behalf of Advanced Accelerator Applications, Novocure Inc, Nuvalent, Pfizer Inc, Pharmacyclics LLC, an AbbVie Company, Puma Biotechnology Inc, Regeneron Pharmaceuticals Inc, Rigel Pharmaceuticals Inc, R-Pharm US, Sanofi, Seagen Inc, Servier Pharmaceuticals LLC, SpringWorks Therapeutics Inc, Stemline Therapeutics Inc, Sumitomo Pharma America, Syndax Pharmaceuticals, Taiho Oncology Inc, Takeda Pharmaceuticals USA Inc, TerSera Therapeutics LLC, and Tesaro, A GSK Company.

RESEARCH TO PRACTICE CME PLANNING COMMITTEE MEMBERS, STAFF AND REVIEWERS — Planners, scientific staff and independent reviewers for Research To Practice have no relevant financial relationships to disclose.

These educational activities contain discussion of published and/or investigational uses of agents that are not indicated by the Food and Drug Administration. Research To Practice does not recommend the use of any agent outside of the labeled indications. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications and warnings. The opinions expressed are those of the presenters and are not to be construed as those of the publisher or grantors.

These activities are supported by educational grants from AstraZeneca Pharmaceuticals LP and Stemline Therapeutics Inc.

Release date: October 2025
Expiration date: October 2026

After completing the post-test, learners may download and review the answers here in order to identify further areas of study.

Dr Shatsky

Allouchery V et al. Circulating ESR1 mutations at the end of aromatase inhibitor adjuvant treatment and after relapse in breast cancer patients. Breast Cancer Res 2018;20(1):40. Abstract

Benvenuti C et al. Unveiling the potential of cyclin-dependent kinases 4 and 6 inhibitors beyond progression in hormone receptor positive/human epidermal growth factor negative advanced breast cancer — A clinical review. Curr Treat Options Oncol 2024;25(12):1517-137. Abstract

Bielo LB et al. Genomic and clinical landscape of metastatic hormone receptors-positive breast cancers carrying ESR1 alterations. ESMO Open 2024;9(10):103731. Abstract

Brett JO et al. ESR1 mutation as an emerging clinical biomarker in metastatic hormone receptor-positive breast cancer. Breast Cancer Res 2021;23(1):85. Abstract

Burstein HJ et al. Testing for ESR1 mutations to guide therapy for hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer: ASCO guideline Rapid Recommendations Update. J Clin Oncol 2023;41(18):3423-5. Abstract

Chandarlapaty S et al. Prevalence of ESR1 mutations in cell-free DNA and outcomes in metastatic breast cancer: A secondary analysis of the BOLERO-2 clinical trial. JAMA Oncol 2016;2(10):1310-5. Abstract

Chaudhary N et al. CDK4/6i-treated HR+/HER2- breast cancer tumors show higher ESR1 mutation prevalence and more altered genomic landscape. NPJ Breast Cancer 2024;10(1):15. Abstract

Jeselsohn R et al. Allele-specific chromatin recruitment and therapeutic vulnerabilities of ESR1 activating mutations. Cancer Cell 2018;33(2):173-86.e5. Abstract

Neupane N et al. Oral SERD, a novel endocrine therapy for estrogen receptor-positive breast cancer. Cancers (Basel) 2024;16(3):619. Abstract

Sivakumar S et al. Tissue and liquid biopsy profiling reveal convergent tumor evolution and therapy evasion in breast cancer. Nat Commun 2022;13(1):7495. Abstract

Toy W et al. Activating ESR1 mutations differentially affect the efficacy of ER antagonists. Cancer Discov 2017;7(3):277-87. Abstract

Turner NC et al. ESR1 mutations and overall survival on fulvestrant versus exemestane in advanced hormone receptor-positive breast cancer: A combined analysis of the phase III SoFEA and EFECT trials. Clin Cancer Res 2020;26(19):5172-7. Abstract

 

Dr Wander

Bardia A et al. Elacestrant in ER+, HER2- metastatic breast cancer with ESR1-mutated tumors: Subgroup analyses from the phase III EMERALD trial by prior duration of endocrine therapy plus CDK4/6 inhibitor and in clinical subgroups. Clin Cancer Res 2024;30(19):4299-309. Abstract

Bidard F-C et al. First-line camizestrant for emerging ESR1-mutated advanced breast cancer. N Engl J Med 2025;393(6):569-80. Abstract

Bidard F-C et al. Elacestrant (oral selective estrogen receptor degrader) versus standard endocrine therapy for estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: Results from the randomized phase III EMERALD trial. J Clin Oncol 2022;40(28):3246-56. Abstract

Guglielmi G et al. Pharmacological insights on novel oral selective estrogen receptor degraders in breast cancer. Eur J Pharmacol 2024;969:176424. Abstract

Jhaveri KL et al. Imlunestrant with or without abemaciclib in advanced breast cancer. N Engl J Med 2025;392(12):1189-202. Abstract

Jhaveri KL et al. Imlunestrant, an oral selective estrogen receptor degrader, as monotherapy and in combination with targeted therapy in estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: Phase Ia/Ib EMBER study. J Clin Oncol 2024;42(35):4173-86. Abstract

Lloyd M et al. Impact of prior treatment, ESR1 mutational (ESR1m) landscape, and co-occurring PI3K pathway status on real-world (RW) elacestrant outcomes in patients (pts) with hormone receptor-positive (HR+)/HER2-negative advanced breast cancer (aBC). San Antonio Breast Cancer Symposium 2024;Abstract PS7-05.

Martin M et al. Giredestrant for estrogen receptor–positive, HER2-negative, previously treated advanced breast cancer: Results from the randomized, phase II acelERA breast cancer study. J Clin Oncol 2024;42(18):2149-60. Abstract

Oliveira M et al. Camizestrant, a next generation oral SERD vs fulvestrant in post-menopausal women with advanced ER-positive HER2-negative breast cancer: Results of the randomized, multi-dose phase 2 SERENA-2 trial. San Antonio Breast Cancer Symposium 2022;Abstract GS3-02.

Patel R et al. An emerging generation of endocrine therapies in breast cancer: A clinical perspective. NPJ Breast Cancer 2023;9(1):20. Abstract

Teysir J et al. After a CDK4/6 inhibitor: State of the art in hormone receptor-positive metastatic breast cancer. Am Soc Clin Oncol Educ Book 2025;45(3):e473372. Abstract

Tolaney SM et al. AMEERA-3: Randomized phase II study of amcenestrant (oral selective estrogen receptor degrader) versus standard endocrine monotherapy in estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. J Clin Oncol 2023;41(24):4014-24. Abstract

Toy W et al. Activating ESR1 mutations differentially affect the efficacy of ER antagonists. Cancer Discov 2017;7(3):277-87. Abstract

Turner N et al. Design of SERENA-6, a phase III switching trial of camizestrant in ESR1-mutant breast cancer during first-line treatment. Future Oncol 2023;19(8):559-73. Abstract

 

Prof Bidard

Baird RD et al. Camizestrant in combination with three globally approved CDK4/6 inhibitors in women with ER+, HER2− advanced breast cancer: Results from SERENA-1. Clin Cancer Res 2025;[Online ahead of print]. Abstract

Bidard F-C et al. First-line camizestrant for emerging ESR1-mutated advanced breast cancer. N Engl J Med 2025;393(6):569-80. Abstract

Jhaveri KL et al. Imlunestrant, an oral selective estrogen receptor degrader, as monotherapy and in combination with targeted therapy in estrogen receptor–positive, human epidermal growth factor receptor 2–negative advanced breast cancer: Phase Ia/Ib EMBER study. J Clin Oncol 2024;42(35):4173-86. Abstract

Rugo HS et al. Elacestrant in various combinations in patients (pts) with estrogen receptor-positive (ER+), HER2-negative (HER2-) locally advanced or metastatic breast cancer (adv/mBC): Preliminary data from ELEVATE, a phase 1b/2, open-label, umbrella study. ASCO 2024;Abstract 1069.

 

Dr Rugo

Bidard F-C et al. First-line camizestrant for emerging ESR1-mutated advanced breast cancer. N Engl J Med 2025;393(6):569-80. Abstract

Bidard F-C et al. Elacestrant (oral selective estrogen receptor degrader) versus standard endocrine therapy for estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: Results from the randomized phase III EMERALD trial. J Clin Oncol 2022;40(28):3246-56. Abstract

Campone M et al. Vepdegestrant, a PROTAC estrogen receptor degrader, in advanced breast cancer. N Engl J Med 2025;393(6):556-8. Abstract

Chan N et al. Elacestrant combinations in patients (pts) with ER+/HER2- locally advanced or metastatic breast cancer (mBC): Safety update from ELEVATE, a phase (Ph) 1b/2, open-label, umbrella study. ASCO 2025;Abstract 1079.

Cortés J et al. EMERALD trial analysis of patient-reported outcomes (PROs) in patients with ER+/HER2− advanced or metastatic breast cancer (mBC) comparing oral elacestrant vs standard of care (SoC) endocrine therapy. ESMO Breast 2023;Abstract 188O.

Curigliano G et al. Patient-reported outcomes (PROs) in patients with ER+, HER2- advanced breast cancer (ABC) treated with imlunestrant, investigator’s choice standard endocrine therapy, or imlunestrant + abemaciclib: Results from the phase III EMBER-3 trial. ASCO 2025;Abstract 1001.

Hamilton EP et al. Vepdegestrant, a PROTAC estrogen receptor (ER) degrader, vs fulvestrant in ER-positive/human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer: Results of the global, randomized, phase 3 VERITAC-2 study. ASCO 2025;Abstract LBA1000.

Jhaveri K et al. Imlunestrant, an oral selective estrogen receptor degrader (SERD), as monotherapy & combined with abemaciclib, for patients with ER+, HER2- advanced breast cancer (ABC), pretreated with endocrine therapy (ET): Results of the phase 3 EMBER-3 trial. San Antonio Breast Cancer Symposium 2024;Abstract GS1-01.

Kaklamani VG et al. Oral elacestrant vs standard-of-care in estrogen receptor-positive, HER2-negative (ER+/HER2-) advanced or metastatic breast cancer (mBC) without detectable ESR1 mutation (EMERALD): Subgroup analysis by prior duration of CDK4/6i plus endocrine therapy (ET). ASCO 2023;Abstract 1070.

Oliveira M et al. Camizestrant, a next-generation oral SERD, versus fulvestrant in post-menopausal women with oestrogen receptor-positive, HER2-negative advanced breast cancer (SERENA-2): A multi-dose, open-label, randomised, phase 2 trial. Lancet Oncol 2024;25(11):1424-39. Abstract

Oliveira M et al. Camizestrant, a next generation oral SERD vs fulvestrant in post-menopausal women with advanced ER-positive HER2-negative breast cancer: Results of the randomized, multi-dose phase 2 SERENA-2 trial. San Antonio Breast Cancer Symposium 2022;Abstract GS3-02.

Rugo HS et al. Elacestrant (Ela) combinations with ribociclib (Ribo) and everolimus (Eve) in patients (pts) with ER+/HER2- locally advanced or metastatic breast cancer (mBC): Update from ELEVATE, a phase (Ph) 1b/2, open-label, umbrella study. ASCO 2025;Abstract 1070.

Turner NC et al. INAVO120: Phase III trial final overall survival (OS) analysis of first-line inavolisib (INAVO)/placebo (PBO) + palbociclib (PALBO) + fulvestrant (FULV) in patients (pts) with PIK3CA-mutated, hormone receptor-positive (HR+), HER2-negative (HER2–), endocrine-resistant advanced breast cancer (aBC). ASCO 2025;Abstract 1003.

Faculty

TARGET AUDIENCE
This activity is intended for medical oncologists, hematology-oncology fellows and other healthcare providers involved in the treatment of breast cancer.

LEARNING OBJECTIVES

• Define endocrine resistance in patients with HR-positive metastatic breast cancer (mBC), and integrate available nonhormonal therapies into the care of these individuals.
• Consider relevant biological, patient, psychosocial and treatment-related factors to personalize the selection and sequencing of therapy for individuals diagnosed with endocrine therapy resistant HR-positive mBC.
• Appraise available clinical research results establishing the safety and efficacy of HER2-directed antibody-drug conjugates (ADCs) for patients with HR-positive, HER2-low and HER2-ultralow mBC, and formulate a plan to optimally incorporate this therapeutic strategy into the treatment algorithm for appropriately selected patients.
• Interrogate published Phase III research findings documenting the efficacy of TROP2-directed ADCs for patients with HR-positive mBC to determine the current clinical applicability of these approaches.

ACCREDITATION STATEMENT
Research To Practice is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

CREDIT DESIGNATION STATEMENT
CME credit is no longer available for this issue.

AMERICAN BOARD OF INTERNAL MEDICINE (ABIM) — MAINTENANCE OF CERTIFICATION (MOC)
CME credit is no longer available for this issue.

AMERICAN BOARD OF SURGERY (ABS) — CONTINUOUS CERTIFICATION (CC)
CME credit is no longer available for this issue.

PRIVACY POLICY
Personal information and data sharing: Research To Practice aggregates deidentified user data for program-use analysis, program development, activity planning and site improvement. We may provide aggregate and deidentified data to third parties, including commercial supporters. We do not share or sell personally identifiable information to any unaffiliated third parties or commercial supporters. Please see our privacy policy at ResearchToPractice.com/Privacy-Policy for more information.

HOW TO USE THIS CME ACTIVITY
CME credit is no longer available for this issue.

CONTENT VALIDATION AND DISCLOSURES
Research To Practice (RTP) is committed to providing its participants with high-quality, unbiased and state-of-the-art education and adheres to the ACCME’s Standards for Integrity and Independence in Accredited Continuing Education. Any individuals in a position to control the content of an accredited continuing education activity, including faculty, planners, reviewers and others, are required to disclose all relevant financial relationships with ineligible entities (commercial interests). All relevant financial relationships have been mitigated prior to the commencement of this activity. In addition, all activity content is reviewed by RTP scientific staff and an external, independent physician reviewer for fair balance, scientific objectivity of studies referenced and patient care recommendations.

FACULTY — The following faculty reported relevant financial relationships with ineligible entities:

Hope S Rugo, MD
Director, Women’s Cancers Program
Division Chief, Breast Medical Oncology
Professor, Department of Medical Oncology and Therapeutics Research
City of Hope Comprehensive Cancer Center
Duarte, California
Professor Emeritus, UCSF

Advisory Committees: Bristol Myers Squibb, Chugai Pharmaceutical Co Ltd, Napo Pharmaceuticals Inc, Sanofi, Viatris; Contracted Research (Institutional Research Support): Ambrx, AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, Genentech, a member of the Roche Group, Gilead Sciences Inc, Lilly, Merck, Novartis, OBI Pharma Inc, Pfizer Inc, Stemline Therapeutics Inc.

EDITOR — Dr Love is president and CEO of Research To Practice. Research To Practice receives funds in the form of educational grants to develop CME activities from the following companies: Aadi Bioscience, AbbVie Inc, ADC Therapeutics, Alexion Pharmaceuticals, Amgen Inc, Array BioPharma Inc, a subsidiary of Pfizer Inc, Arvinas, Astellas, AstraZeneca Pharmaceuticals LP, Aveo Pharmaceuticals, Bayer HealthCare Pharmaceuticals, BeiGene Ltd, Black Diamond Therapeutics Inc, Blueprint Medicines, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, Clovis Oncology, Coherus BioSciences, CTI BioPharma, a Sobi Company, Daiichi Sankyo Inc, Eisai Inc, Elevation Oncology Inc, Exact Sciences Corporation, Exelixis Inc, Genentech, a member of the Roche Group, Genmab US Inc, Geron Corporation, Gilead Sciences Inc, GSK, Hologic Inc, ImmunoGen Inc, Incyte Corporation, Ipsen Biopharmaceuticals Inc, Jazz Pharmaceuticals Inc, Johnson & Johnson, Karyopharm Therapeutics, Kite, A Gilead Company, Kura Oncology, Legend Biotech, Lilly, MEI Pharma Inc, Merck, Mersana Therapeutics Inc, Mirati Therapeutics Inc, Mural Oncology Inc, Natera Inc, Novartis, Novartis Pharmaceuticals Corporation on behalf of Advanced Accelerator Applications, Novocure Inc, Nuvalent, Pfizer Inc, Pharmacyclics LLC, an AbbVie Company, Puma Biotechnology Inc, Regeneron Pharmaceuticals Inc, Rigel Pharmaceuticals Inc, R-Pharm US, Sanofi, Seagen Inc, Servier Pharmaceuticals LLC, SpringWorks Therapeutics Inc, Stemline Therapeutics Inc, Syndax Pharmaceuticals, Taiho Oncology Inc, Takeda Pharmaceuticals USA Inc, TerSera Therapeutics LLC, and Tesaro, A GSK Company.

RESEARCH TO PRACTICE CME PLANNING COMMITTEE MEMBERS, STAFF AND REVIEWERS — Planners, scientific staff and independent reviewers for Research To Practice have no relevant financial relationships to disclose.

These educational activities contain discussion of published and/or investigational uses of agents that are not indicated by the Food and Drug Administration. Research To Practice does not recommend the use of any agent outside of the labeled indications. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications and warnings. The opinions expressed are those of the presenters and are not to be construed as those of the publisher or grantors.

These activities are supported by educational grants from AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, and Gilead Sciences Inc.

Release date: July 2025
Expiration date: July 2026

Baird R et al. Puxitatug samrotecan (P-Sam, AZD8205) in patients with HR+/HER2– breast cancer: A first-in-human Phase 1/2a dose escalation and expansion study. ESMO Breast 2025;Abstract 300MO

Bardia A et al. Datopotamab deruxtecan versus chemotherapy in previously treated inoperable/metastatic hormone receptor-positive human epidermal growth factor receptor 2-negative breast cancer: Primary results from TROPION-Breast01. J Clin Oncol 2025;43(3):285-96. Abstract

Bardia A et al. Efficacy and safety of trastuzumab deruxtecan (T-DXd) vs physician’s choice of chemotherapy (TPC) by pace of disease progression on prior endocrine-based therapy: Additional analysis from DESTINY-Breast06. San Antonio Breast Cancer Symposium 2024;Abstract LB1-04.

Bardia A et al. Trastuzumab deruxtecan after endocrine therapy in metastatic breast cancer. N Engl J Med 2024;391(22):2110-22. Abstract

Colombo R et al. The journey of antibody-drug conjugates: Lessons learned from 40 years of development. Cancer Discov 2024;14(11):2089-108. Abstract

Curigliano G et al. Trastuzumab deruxtecan (T-DXd) vs physician’s choice of chemotherapy (TPC) in patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-low or HER2-ultralow metastatic breast cancer (mBC) with prior endocrine therapy (ET): Primary results from DESTINY-Breast06 (DB-06). ASCO 2024;Abstract LBA1000.

Hamilton EP et al. Vepdegestrant, a PROTAC estrogen receptor (ER) degrader, vs fulvestrant in ER-positive/human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer: Results of the global, randomized, phase 3 VERITAC-2 study. ASCO 2025;Abstract LBA1000.

Khan A et al. Mechanisms and therapeutic strategies for endocrine resistance in breast cancer: A comprehensive review and meta-analysis. Cancers (Basel) 2025;17(10):1653. Abstract

Oliveira M et al. Primary results of SOLTI VALENTINE: Neoadjuvant randomized phase II trial of HER3-DXd alone or in combination with letrozole for high-risk hormone receptor positive (HR+)/HER2-negative (neg) early breast cancer (EBC). San Antonio Breast Cancer Symposium 2024;Abstract LBA1-06.

Pérez García JM et al. Prevention of sacituzumab govitecan (SG)-related neutropenia and diarrhea in patients (pts) with triple-negative or HR+/HER2- advanced breast cancer (ABC; PRIMED): A phase 2 trial. ASCO 2024;Abstract 1101.

Pistilli B et al. Datopotamab deruxtecan (Dato-DXd) vs chemotherapy (CT) in previously-treated inoperable or metastatic hormone receptor-positive, HER2-negative (HR+/HER2–) breast cancer (BC): Final overall survival (OS) from the phase III TROPION-Breast01 trial. ESMO Virtual Plenary 2023;Abstract VP1-2025

Faculty

TARGET AUDIENCE
This activity is intended for medical oncologists, hematology-oncology fellows and other healthcare providers involved in the treatment of breast cancer.

LEARNING OBJECTIVES

• Define endocrine resistance in patients with HR-positive metastatic breast cancer (mBC), and integrate available nonhormonal therapies into the care of these individuals.
• Consider relevant biological, patient, psychosocial and treatment-related factors to personalize the selection and sequencing of therapy for individuals diagnosed with endocrine therapy resistant HR-positive mBC.
• Appraise available clinical research results establishing the safety and efficacy of HER2-directed antibody-drug conjugates (ADCs) for patients with HR-positive, HER2-low and HER2-ultralow mBC, and formulate a plan to optimally incorporate this therapeutic strategy into the treatment algorithm for appropriately selected patients.
• Interrogate published Phase III research findings documenting the efficacy of TROP2-directed ADCs for patients with HR-positive mBC to determine the current clinical applicability of these approaches.

ACCREDITATION STATEMENT
Research To Practice is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

CREDIT DESIGNATION STATEMENT
CME credit is no longer available for this issue.

AMERICAN BOARD OF INTERNAL MEDICINE (ABIM) — MAINTENANCE OF CERTIFICATION (MOC)
CME credit is no longer available for this issue.

AMERICAN BOARD OF SURGERY (ABS) — CONTINUOUS CERTIFICATION (CC)
CME credit is no longer available for this issue.

PRIVACY POLICY
Personal information and data sharing: Research To Practice aggregates deidentified user data for program-use analysis, program development, activity planning and site improvement. We may provide aggregate and deidentified data to third parties, including commercial supporters. We do not share or sell personally identifiable information to any unaffiliated third parties or commercial supporters. Please see our privacy policy at ResearchToPractice.com/Privacy-Policy for more information.

HOW TO USE THIS CME ACTIVITY
CME credit is no longer available for this issue.

CONTENT VALIDATION AND DISCLOSURES
Research To Practice (RTP) is committed to providing its participants with high-quality, unbiased and state-of-the-art education and adheres to the ACCME’s Standards for Integrity and Independence in Accredited Continuing Education. Any individuals in a position to control the content of an accredited continuing education activity, including faculty, planners, reviewers and others, are required to disclose all relevant financial relationships with ineligible entities (commercial interests). All relevant financial relationships have been mitigated prior to the commencement of this activity. In addition, all activity content is reviewed by RTP scientific staff and an external, independent physician reviewer for fair balance, scientific objectivity of studies referenced and patient care recommendations.

FACULTY — The following faculty reported relevant financial relationships with ineligible entities:

Hope S Rugo, MD
Director, Women’s Cancers Program
Division Chief, Breast Medical Oncology
Professor, Department of Medical Oncology and Therapeutics Research
City of Hope Comprehensive Cancer Center
Duarte, California
Professor Emeritus, UCSF

Advisory Committees: Bristol Myers Squibb, Chugai Pharmaceutical Co Ltd, Napo Pharmaceuticals Inc, Sanofi, Viatris; Contracted Research (Institutional Research Support): Ambrx, AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, Genentech, a member of the Roche Group, Gilead Sciences Inc, Lilly, Merck, Novartis, OBI Pharma Inc, Pfizer Inc, Stemline Therapeutics Inc.

EDITOR — Dr Love is president and CEO of Research To Practice. Research To Practice receives funds in the form of educational grants to develop CME activities from the following companies: Aadi Bioscience, AbbVie Inc, ADC Therapeutics, Alexion Pharmaceuticals, Amgen Inc, Array BioPharma Inc, a subsidiary of Pfizer Inc, Arvinas, Astellas, AstraZeneca Pharmaceuticals LP, Aveo Pharmaceuticals, Bayer HealthCare Pharmaceuticals, BeiGene Ltd, Black Diamond Therapeutics Inc, Blueprint Medicines, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, Clovis Oncology, Coherus BioSciences, CTI BioPharma, a Sobi Company, Daiichi Sankyo Inc, Eisai Inc, Elevation Oncology Inc, Exact Sciences Corporation, Exelixis Inc, Genentech, a member of the Roche Group, Genmab US Inc, Geron Corporation, Gilead Sciences Inc, GSK, Hologic Inc, ImmunoGen Inc, Incyte Corporation, Ipsen Biopharmaceuticals Inc, Jazz Pharmaceuticals Inc, Johnson & Johnson, Karyopharm Therapeutics, Kite, A Gilead Company, Kura Oncology, Legend Biotech, Lilly, MEI Pharma Inc, Merck, Mersana Therapeutics Inc, Mirati Therapeutics Inc, Mural Oncology Inc, Natera Inc, Novartis, Novartis Pharmaceuticals Corporation on behalf of Advanced Accelerator Applications, Novocure Inc, Nuvalent, Pfizer Inc, Pharmacyclics LLC, an AbbVie Company, Puma Biotechnology Inc, Regeneron Pharmaceuticals Inc, Rigel Pharmaceuticals Inc, R-Pharm US, Sanofi, Seagen Inc, Servier Pharmaceuticals LLC, SpringWorks Therapeutics Inc, Stemline Therapeutics Inc, Syndax Pharmaceuticals, Taiho Oncology Inc, Takeda Pharmaceuticals USA Inc, TerSera Therapeutics LLC, and Tesaro, A GSK Company.

RESEARCH TO PRACTICE CME PLANNING COMMITTEE MEMBERS, STAFF AND REVIEWERS — Planners, scientific staff and independent reviewers for Research To Practice have no relevant financial relationships to disclose.

These educational activities contain discussion of published and/or investigational uses of agents that are not indicated by the Food and Drug Administration. Research To Practice does not recommend the use of any agent outside of the labeled indications. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications and warnings. The opinions expressed are those of the presenters and are not to be construed as those of the publisher or grantors.

These activities are supported by educational grants from AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, and Gilead Sciences Inc.

Release date: July 2025
Expiration date: July 2026

Baird R et al. Puxitatug samrotecan (P-Sam, AZD8205) in patients with HR+/HER2– breast cancer: A first-in-human Phase 1/2a dose escalation and expansion study. ESMO Breast 2025;Abstract 300MO

Bardia A et al. Datopotamab deruxtecan versus chemotherapy in previously treated inoperable/metastatic hormone receptor-positive human epidermal growth factor receptor 2-negative breast cancer: Primary results from TROPION-Breast01. J Clin Oncol 2025;43(3):285-96. Abstract

Bardia A et al. Efficacy and safety of trastuzumab deruxtecan (T-DXd) vs physician’s choice of chemotherapy (TPC) by pace of disease progression on prior endocrine-based therapy: Additional analysis from DESTINY-Breast06. San Antonio Breast Cancer Symposium 2024;Abstract LB1-04.

Bardia A et al. Trastuzumab deruxtecan after endocrine therapy in metastatic breast cancer. N Engl J Med 2024;391(22):2110-22. Abstract

Colombo R et al. The journey of antibody-drug conjugates: Lessons learned from 40 years of development. Cancer Discov 2024;14(11):2089-108. Abstract

Curigliano G et al. Trastuzumab deruxtecan (T-DXd) vs physician’s choice of chemotherapy (TPC) in patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-low or HER2-ultralow metastatic breast cancer (mBC) with prior endocrine therapy (ET): Primary results from DESTINY-Breast06 (DB-06). ASCO 2024;Abstract LBA1000.

Hamilton EP et al. Vepdegestrant, a PROTAC estrogen receptor (ER) degrader, vs fulvestrant in ER-positive/human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer: Results of the global, randomized, phase 3 VERITAC-2 study. ASCO 2025;Abstract LBA1000.

Khan A et al. Mechanisms and therapeutic strategies for endocrine resistance in breast cancer: A comprehensive review and meta-analysis. Cancers (Basel) 2025;17(10):1653. Abstract

Oliveira M et al. Primary results of SOLTI VALENTINE: Neoadjuvant randomized phase II trial of HER3-DXd alone or in combination with letrozole for high-risk hormone receptor positive (HR+)/HER2-negative (neg) early breast cancer (EBC). San Antonio Breast Cancer Symposium 2024;Abstract LBA1-06.

Pérez García JM et al. Prevention of sacituzumab govitecan (SG)-related neutropenia and diarrhea in patients (pts) with triple-negative or HR+/HER2- advanced breast cancer (ABC; PRIMED): A phase 2 trial. ASCO 2024;Abstract 1101.

Pistilli B et al. Datopotamab deruxtecan (Dato-DXd) vs chemotherapy (CT) in previously-treated inoperable or metastatic hormone receptor-positive, HER2-negative (HR+/HER2–) breast cancer (BC): Final overall survival (OS) from the phase III TROPION-Breast01 trial. ESMO Virtual Plenary 2023;Abstract VP1-2025

Faculty

TARGET AUDIENCE
This program is intended for medical and radiation oncologists, hematologists, hematology-oncology fellows, general and breast surgeons and other healthcare providers involved in the treatment of breast cancer.

LEARNING OBJECTIVES

• Evaluate recently presented clinical research findings to determine their effect on the current management of metastatic breast cancer (mBC).
• Review the correlation between various biomarkers (eg, PIK3CA/AKT1/PTEN alterations, ESR1 mutations, low and ultralow HER2 levels) and response to specific therapies, and develop optimal testing algorithms for patients with hormone receptor (HR)-positive mBC.
• Appraise published efficacy and safety data from randomized clinical trials evaluating CDK4/6 inhibitors for HR-positive mBC, and appropriately counsel patients regarding the optimal use of these agents.
• Recall the frequency of phosphoinositide-3 kinase pathway mutations in patients with HR-positive mBC, and recognize the evidence-based approaches available to target these aberrations in individuals with PIK3CA-mutated disease.
• Understand the mechanism of action of, published and emerging research findings with and the current and future clinical role of oral selective estrogen receptor degraders for patients with HR-positive mBC harboring ESR1 mutations.
• Interrogate published Phase III research documenting the efficacy of AKT inhibitors for patients with progressive HR-positive mBC to determine the current clinical applicability of this approach.
• Appreciate the incidence, characteristics and clinical relevance of HER2-low or ultralow mBC, and understand available research findings with HER2-directed antibody-drug conjugates for this disease subset.
• Assess published and emerging Phase III research documenting the efficacy of TROP2-directed antibody-drug conjugates for mBC in order to determine the current and potential clinical applicability of these approaches.
• Evaluate published and emerging research findings and biological and clinical factors to effectively select and sequence available therapeutic agents and regimens for patients with HER2-positive mBC.
• Review published research supporting the use of chemotherapy in combination with anti-PD-1/PD-L1 antibodies for patients with triple-negative mBC, and use this information to make appropriate treatment recommendations.
• Discuss available research establishing the efficacy of PARP inhibitors for patients with mBC harboring BRCA or other homologous recombination repair pathway mutations, and identify individuals appropriate for treatment with these agents.
• Recall the mechanisms of action of, early data with and ongoing clinical trials evaluating other novel agents and treatment strategies under development for mBC.

ACCREDITATION STATEMENT
Research To Practice is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

CREDIT DESIGNATION STATEMENT
CME credit is no longer available for this issue.

AMERICAN BOARD OF INTERNAL MEDICINE (ABIM) — MAINTENANCE OF CERTIFICATION (MOC)
CME credit is no longer available for this issue.

AMERICAN BOARD OF SURGERY (ABS) — CONTINOUS CERTIFICATION (CC)
Successful completion of these CME activities, which includes participation in the evaluation component and a post-test, enables the learner to earn credit toward the CME and Self-Assessment requirement(s) of the American Board of Surgery’s Continuous Certification program. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABS credit.

Please note, these programs have been specifically designed for the following ABS practice area: complex general surgical oncology.

PRIVACY POLICY
Personal information and data sharing: Research To Practice aggregates deidentified user data for program-use analysis, program development, activity planning and site improvement. We may provide aggregate and deidentified data to third parties, including commercial supporters. We do not share or sell personally identifiable information to any unaffiliated third parties or commercial supporters. Please see our privacy policy at ResearchToPractice.com/Privacy-Policy for more information.

HOW TO USE THIS CME ACTIVITY
Video Program: This CME activity consists of a video component. To receive credit, the participant should review the CME information, watch the video, complete the post-test with a score of 80% or better and fill out the evaluation located at ResearchToPractice.com/ASCO2025/mBC/Video/CME.

CONTENT VALIDATION AND DISCLOSURES
Research To Practice (RTP) is committed to providing its participants with high-quality, unbiased and state-of-the-art education and adheres to the ACCME’s Standards for Integrity and Independence in Accredited Continuing Education. Any individuals in a position to control the content of an accredited continuing education activity, including faculty, planners, reviewers and others, are required to disclose all relevant financial relationships with ineligible entities (commercial interests). All relevant financial relationships have been mitigated prior to the commencement of this activity. In addition, all activity content is reviewed by RTP scientific staff and an external, independent physician reviewer for fair balance, scientific objectivity of studies referenced and patient care recommendations.

FACULTY — The following faculty reported relevant financial relationships with ineligible entities:

Harold J Burstein, MD, PhD
Director of Academic Partnerships
Institute Physician
Dana-Farber Cancer Institute
Professor of Medicine
Harvard Medical School
Boston, Massachusetts

No relevant financial relationships to disclose

Javier Cortés, MD, PhD
Head, IBCC International Breast Cancer Center
Barcelona, Spain

Consulting and Advisor: AbbVie Inc, AstraZeneca Pharmaceuticals LP, AvenCell Europe GmbH, Bioasis Technologies Inc, Biocon, BioInvent, BioNTech SE, Bliss Biopharmaceutical (Hangzhou) Co Ltd, Boehringer Ingelheim Pharmaceuticals Inc, Circle Pharma, Daiichi Sankyo Inc, Delcath Systems Inc, Ellipses Pharma, ExpreS2ion Biotechnologies, Gilead Sciences Inc, Hexagon Bio, HiberCell, Jazz Pharmaceuticals Inc, Leuko Labs Inc, Lilly, Menarini Group, MSD, pharmaand GmbH, QED Therapeutics, Reveal Genomics, Roche Laboratories Inc, Seagen Inc, Zymeworks Inc; Contracted Research Funding to Institution: AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, Eisai Inc, F Hoffmann-La Roche Ltd, Guardant Health, IQVIA, MSD, Pfizer Inc, PIQUR Therapeutics, Queen Mary University of London, Roche Laboratories Inc, Servier Affaires Medicales, Takeda Pharmaceuticals USA Inc; Honoraria: AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, Eisai Inc, Gilead Sciences Inc, Lilly, MSD, Novartis, Pfizer Inc, Roche Laboratories Inc, Stemline Therapeutics Inc, Zuellig Pharma; Patents: WO 2014/199294 A, US 2019/0338368 A1; Stock Options/Stock — Public Companies: Leuko Labs Inc; Travel, Accommodation, Expenses: AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, Eisai Inc, Gilead Sciences Inc, MSD, Novartis, Pfizer Inc, Roche Laboratories Inc, Stemline Therapeutics Inc; Nonrelevant Financial Relationships: MAJ3 Capital.

Rebecca A Dent, MD, MSc
Senior Consultant
National Cancer Centre Singapore
Singapore

No relevant financial relationships to disclose.

Kevin Kalinsky, MD, MS, FASCO
Professor of Medicine
Director, Division of Medical Oncology
Director, Glenn Family Breast Center
Winship Cancer Institute at Emory University
Atlanta, Georgia

Advisory Committees: AstraZeneca Pharmaceuticals LP, Biotheranostics Inc, Daiichi Sankyo Inc, Genentech, a member of the Roche Group, Gilead Sciences Inc, Lilly, Menarini Silicon Biosystems, Merck, Mersana Therapeutics Inc, Myovant Sciences, Novartis, Pfizer Inc, ProteinQure, Puma Biotechnology Inc, Regor Therapeutics, Relay Therapeutics, Seagen Inc.

Joyce O’Shaughnessy, MD
Celebrating Women Chair in Breast Cancer Research
Baylor University Medical Center
Chair, Breast Disease Committee
Sarah Cannon Research Institute
Dallas, Texas

Advisory Committees and Consulting Agreements: Aadi Bioscience, Agendia Inc, Amgen Inc, Aptitude Health, AstraZeneca Pharmaceuticals LP, BioNTech SE, Bristol Myers Squibb, Daiichi Sankyo Inc, Duality Biologics, Eisai Inc, Ellipses Pharma, Exact Sciences Corporation, G1 Therapeutics Inc, Genentech, a member of the Roche Group, Gilead Sciences Inc, Guardant Health, HiberCell, Jazz Pharmaceuticals Inc, Johnson & Johnson, Lilly, Merck, Mersana Therapeutics Inc, Natera Inc, Novartis, Pfizer Inc, Pierre Fabre, Puma Biotechnology Inc, RayzeBio Inc, Roche Laboratories Inc, Sanofi, Seagen Inc, Stemline Therapeutics Inc, Summit Therapeutics, Tempus, TerSera Therapeutics LLC.

SURVEY PARTICIPANTS
Sara A Hurvitz, MD, FACP — Contracted Research: Ambrx, Amgen Inc, Arvinas, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, Celcuity, CytomX Therapeutics, Daiichi Sankyo Inc, Dantari, Dignitana AB, G1 Therapeutics Inc, Genentech, a member of the Roche Group, Gilead Sciences Inc, Greenwich LifeSciences Inc, GSK, Lilly, MacroGenics Inc, Novartis, OBI Pharma Inc, Orinove Inc, Orum Therapeutics, Pfizer Inc, Phoenix Molecular Designs, Pieris Pharmaceuticals Inc, Puma Biotechnology Inc, Radius Health Inc, Samumed, Sanofi, Seagen Inc, Stemline Therapeutics Inc, Zymeworks Inc. Komal Jhaveri, MD, FACP — Consultant/Advisory Board Roles: AstraZeneca Pharmaceuticals LP, Bicycle Therapeutics, Blueprint Medicines, Daiichi Sankyo Inc, Eisai Inc, Genentech, a member of the Roche Group, Gilead Sciences Inc, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company, Menarini Group, Novartis, Olema Oncology, Pfizer Inc, RayzeBio Inc, Scorpion Therapeutics, Stemline Therapeutics Inc, Zymeworks Inc; Research Funding (Support to Institution): AstraZeneca Pharmaceuticals LP, Blueprint Medicines, Eisai Inc, Genentech, a member of the Roche Group, Gilead Sciences Inc, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company, Merck, Novartis, Pfizer Inc, Puma Biotechnology Inc, RayzeBio Inc, Scorpion Therapeutics, Zymeworks Inc; Travel and Accommodations: AstraZeneca Pharmaceuticals LP, Genentech, a member of the Roche Group, Gilead Sciences Inc, Lilly, Pfizer Inc.

MODERATOR
Hope S Rugo, MD
Director, Women’s Cancers Program
Division Chief, Breast Medical Oncology
Professor, Department of Medical Oncology and Therapeutics Research
City of Hope Comprehensive Cancer Center
Duarte, California
Professor Emeritus, UCSF

Advisory Committees: Bristol Myers Squibb, Chugai Pharmaceutical Co Ltd, Napo Pharmaceuticals Inc, Sanofi, Viatris; Contracted Research (Institutional Research Support): Ambrx, AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, Genentech, a member of the Roche Group, Gilead Sciences Inc, Lilly, Merck, Novartis, OBI Pharma Inc, Pfizer Inc, Stemline Therapeutics Inc.

RESEARCH TO PRACTICE CME PLANNING COMMITTEE MEMBERS, STAFF AND REVIEWERS — Planners, scientific staff and independent reviewers for Research To Practice have no relevant financial relationships to disclose.

These educational activities contain discussion of published and/or investigational uses of agents that are not indicated by the Food and Drug Administration. Research To Practice does not recommend the use of any agent outside of the labeled indications. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications and warnings. The opinions expressed are those of the presenters and are not to be construed as those of the publisher or grantors.

These activities are supported by educational grants from AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, Genentech, a member of the Roche Group, Puma Biotechnology Inc, and Stemline Therapeutics Inc.

Release date: June 2025
Expiration date: June 2026

Dr Cortés

Altaha R et al. Increased risk of brain metastases in patients with HER-2/neu-positive breast carcinoma. Cancer 2005;103(3):442-3. Abstract

Baselga J et al. Case records of the Massachusetts General Hospital. Case 16-2012. A 32-year-old woman with HER2-positive breast cancer. N Engl J Med 2012;366(21):2018-26. Abstract

Bose R et al. Activating HER2 mutations in HER2 gene amplification negative breast cancer. Cancer Discov 2013;3(2):224-37. Abstract

Brufsky A et al. Phase II COLET study: Atezolizumab (A) + cobimetinib (C) + paclitaxel (P)/nab-paclitaxel (nP) as first-line (1L) treatment (tx) for patients (pts) with locally advanced or metastatic triple-negative breast cancer (mTNBC). ASCO 2019;Abstract 1013.

Cortés J et al. Pembrolizumab plus chemotherapy in advanced triple-negative breast cancer. N Engl J Med 2022;387(3):217-26. Abstract

Hyman DM et al. HER kinase inhibition in patients with HER2- and HER3-mutant cancers. Nature 2018;554(7691):189-94. Abstract

Jhaveri K et al. Neratinib + fulvestrant + trastuzumab for HR-positive, HER2-negative, HER2-mutant metastatic breast cancer: outcomes and biomarker analysis from the SUMMIT trial. Ann Oncol 2023;34(10):885-98. Abstract

Lin N et al. Trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2+ advanced/metastatic breast cancer (mBC) with or without brain metastases (BM): DESTINYBreast-12 primary results. ESMO 2024;Abstract LBA18.

Martin M et al. Brain metastases from non-small cell lung carcinoma: An overview of classical and novel treatment strategies. Rep Pract Oncol Radiother 2022;27(3):527-44. Abstract

Metzger O et al. PATINA: A randomized, open label, phase III trial to evaluate the efficacy and safety of palbociclib + anti-HER2 therapy + endocrine therapy vs. anti-HER2 therapy + endocrine therapy after induction treatment for hormone receptor-positive (HR+)/HER2-positive metastatic breast cancer. San Antonio Breast Cancer Symposium 2024;Abstract AFT-38.

Murthy RK et al. Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. N Engl J Med 2020;382(7):597-609. Abstract

Olson EM et al. Clinical outcomes and treatment practice patterns of patients with HER2-positive metastatic breast cancer in the post-trastuzumab era. Breast 2013;22(4):525-31. Abstract

Rugo HS et al. SOPHIA primary analysis: A phase 3 (P3) study of margetuximab (M) + chemotherapy (C) versus trastuzumab (T) + C in patients (pts) with HER2+ metastatic (met) breast cancer (MBC) after prior anti-HER2 therapies (Tx). ASCO 2019;Abstract 1000.

Tolaney S et al. Trastuzumab deruxtecan (T-DXd) + pertuzumab (P) vs taxane + trastuzumab + pertuzumab (THP) for first-line (1L) treatment of patients (pts) with human epidermal growth factor receptor 2–positive (HER2+) advanced/metastatic breast cancer (a/mBC): Interim results from DESTINY-Breast09. ASCO 2025;Abstract LBA1008.

Verma S et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med 2012;367(19):1783-91. Abstract

 

Dr Kalinsky

Allouchery V et al. Circulating ESR1 mutations at the end of aromatase inhibitor adjuvant treatment and after relapse in breast cancer patients. Breast Cancer Res 2018;20(1):40. Abstract

Bardia A et al. Datopotamab deruxtecan (Dato-DXd) vs chemotherapy in previously-treated inoperable or metastatic hormone receptor-positive, HER2-negative (HR+/HER2–) breast cancer (BC): Primary results from the randomised phase III TROPION-Breast01 trial. ESMO 2023;Abstract LBA11.

Brett JO et al. ESR1 mutation as an emerging clinical biomarker in metastatic hormone receptor-positive breast cancer. Breast Cancer Res 2021;23(1):85. Abstract

Brufsky AM. Long-term management of patients with hormone receptor-positive metastatic breast cancer: Concepts for sequential and combination endocrine-based therapies. Cancer Treat Rev 2017;59:22-32. Abstract

Cabel L et al. Dynamics and type of ESR1 mutations under aromatase inhibitor or fulvestrant combined with palbociclib after randomization in the PADA-1 trial. ASCO 2023;Abstract 1002.

Carlson RW et al. Phase II trial of anastrozole plus goserelin in the treatment of hormone receptor-positive, metastatic carcinoma of the breast in premenopausal women. J Clin Oncol 2010;28(25):3917-21. Abstract

Croxtall JD et al. Fulvestrant: A review of its use in the management of hormone receptor-positive metastatic breast cancer in postmenopausal women. Drugs 2011;71(3):363-80. Abstract

Curigliano G et al. Trastuzumab deruxtecan (T-DXd) vs physician’s choice of chemotherapy (TPC) in patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-low or HER2-ultralow metastatic breast cancer (mBC) with prior endocrine therapy (ET): Primary results from DESTINY-Breast06 (DB-06). ASCO 2024;Abstract LBA1000.

Jeselsohn R et al. Allele-specific chromatin recruitment and therapeutic vulnerabilities of ESR1 activating mutations. Cancer Cell 2018;33(2):173-86.e5. Abstract

Jeselsohn R et al. Emergence of constitutively active estrogen receptor-α mutations in pretreated advanced estrogen receptor-positive breast cancer. Clin Cancer Res 2014;20(7):1757-67. Abstract

Lim E et al. The natural history of hormone receptor-positive breast cancer. Oncology (Williston Park) 2012;26(8):688-94, 696. Abstract

Rugo HS et al. Capivasertib (C) and fulvestrant (F) for patients (pts) with aromatase inhibitor (AI)-resistant HR+/HER2– advanced breast cancer (ABC): Characterization and management of common adverse events (AEs) from the phase 3 CAPItello-291 trial. ASCO 2023;Abstract 1067.

Rugo HS et al. Time course and management of key adverse events during the randomized phase III SOLAR-1 study of PI3K inhibitor alpelisib plus fulvestrant in patients with HR-positive advanced breast cancer. Ann Oncol 2020;31(8):1001-10. Abstract

Schiavon G et al. Analysis of ESR1 mutation in circulating tumor DNA demonstrates evolution during therapy for metastatic breast cancer. Sci Transl Med 2015;7(313):313ra182. Abstract

Turner N et al. INAVO120: Phase III trial final overall survival (OS) analysis of first-line inavolisib (INAVO)/placebo (PBO) + palbociclib (PALBO) + fulvestrant (FULV) in patients (pts) with PIK3CA-mutated, hormone receptor-positive (HR+), HER2-negative (HER2–), endocrine-resistant advanced breast cancer (aBC). ASCO 2025;Abstract 1003.

Vasan N et al. At a crossroads: how to translate the roles of PI3K in oncogenic and metabolic signalling into improvements in cancer therapy. Nat Rev Clin Oncol 2022;19(7):471-85. Abstract

 

Dr Burstein

Bardia A et al. Elacestrant in ER+, HER2- metastatic breast cancer with ESR1-mutated tumors: Subgroup analyses from the phase III EMERALD trial by prior duration of endocrine therapy plus CDK4/6 inhibitor and in clinical subgroups. Clin Cancer Res 2024;30(19):4299-309. Abstract

Bardia A et al. Elacestrant vs standard-of-care in ER+/HER2- advanced or metastatic breast cancer (mBC) with ESR1 mutation: Key biomarkers and clinical subgroup analyses from the phase 3 EMERALD trial. San Antonio Breast Cancer Symposium 2023;Abstract PS17-02.

Bidard F-C et al. Elacestrant (oral selective estrogen receptor degrader) versus standard endocrine therapy for estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: Results from the randomized phase III EMERALD trial. J Clin Oncol 2022;40(28):3246-56. Abstract

Hamilton EP et al. Vepdegestrant, a PROTAC estrogen receptor (ER) degrader, vs fulvestrant in ER-positive/human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer: Results of the global, randomized, phase 3 VERITAC-2 study. ASCO 2025;Abstract LBA1000.

Jhaveri KL et al. Imlunestrant with or without abemaciclib in advanced breast cancer. N Engl J Med 2025;392(12):1189-202. Abstract

Jhaveri K et al. Imlunestrant, an oral selective estrogen receptor degrader (SERD), as monotherapy & combined with abemaciclib, for patients with ER+, HER2- advanced breast cancer (ABC), pretreated with endocrine therapy (ET): Results of the phase 3 EMBER-3 trial. San Antonio Breast Cancer Symposium 2024;Abstract GS1-01.

Turner et al. Capivasertib in hormone receptor-positive advanced breast cancer. N Engl J Med 2023;388(22):2058-70. Abstract

 

Dr O’Shaughnessy

Banerji U et al. Trastuzumab duocarmazine in locally advanced and metastatic solid tumours and HER2-expressing breast cancer: A phase 1 dose-escalation and dose-expansion study. Lancet Oncol 2019;20(8):1124-35. Abstract

Bardia A et al. Efficacy and safety of trastuzumab deruxtecan (T-DXd) vs physician’s choice of chemotherapy (TPC) by pace of disease progression on prior endocrine-based therapy: Additional analysis from DESTINY-Breast06. San Antonio Breast Cancer Symposium 2024;Abstract LB1-04.

Bardia A et al. Trastuzumab deruxtecan after endocrine therapy in metastatic breast cancer. N Engl J Med 2024;391(22):2110-22. Abstract

Geukens T et al. Intra-patient and inter-metastasis heterogeneity of HER2-low status in metastatic breast cancer. Eur J Cancer 2023;188:152-60. Abstract

Hurvitz SA et al. TRIO-US B-12 TALENT: Neoadjuvant trastuzumab deruxtecan with or without anastrozole for HER2-low, HR+ early-stage breast cancer. San Antonio Breast Cancer Symposium 2022;Abstract GS2-03.

Miglietta F et al. Evolution of HER2-low expression from primary to recurrent breast cancer. NPJ Breast Cancer 2021;7(1):137. Abstract

Modi S et al. Trastuzumab deruxtecan (T-DXd) versus treatment of physician’s choice (TPC) in patients (pts) with HER2-low unresectable and/or metastatic breast cancer (mBC): Updated survival results of the randomized, phase III DESTINY-Breast04 study. ESMO 2023;Abstract 376O.

Modi S et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med 2022;387(1):9-20. Abstract

Modi S et al. Trastuzumab deruxtecan (T-DXd) versus treatment of physician’s choice (TPC) in patients (pts) with HER2-low unresectable and/or metastatic breast cancer (mBC): Results of DESTINY-Breast04, a randomized, phase 3 study. ASCO 2022;Abstract LBA3.

O’Shaughnessy J et al. DYNASTY-Breast02: A phase III trial of BNT323/DB-1303 vs investigator’s choice chemotherapy in HER2-low, hormone receptor positive, metastatic breast cancer. ESMO 2024;Abstract 436TiP.

Tarantino P et al. Evolution of low HER2 expression between early and advanced-stage breast cancer. Eur J Cancer 2022;163:35-43. Abstract

Wang J et al. RC48-ADC, a HER2-targeting antibody-drug conjugate, in patients with HER2-positive and HER2-low expressing advanced or metastatic breast cancer: A pooled analysis of two studies. ASCO 2021;Abstract 1022.

 

Dr Rugo

Bardia A et al. Datopotamab deruxtecan versus chemotherapy in previously treated inoperable/metastatic hormone receptor-positive human epidermal growth factor receptor 2-negative breast cancer: Primary results from TROPION-Breast01. J Clin Oncol 2025;43(3):285-96. Abstract

Bardia A et al. Randomized phase 3 study of datopotamab deruxtecan vs chemotherapy for patients with previously-treated inoperable or metastatic hormone receptor-positive, HER2-negative breast cancer: Results from TROPION-Breast01. San Antonio Breast Cancer Symposium 2023;Abstract GS02-01.

Columbo R et al. The journey of antibody–drug conjugates: lessons learned from 40 years of development. Cancer Discov 2024;14(11):2089-108. Abstract

Hamilton E et al. Initial phase 1 dose escalation data for emiltatug ledadotin (Emi-Le), a novel B7-H4-directed dolasynthen antibody-drug conjugate. ASCO 2025;Abstract 3009.

Nelson RS et al. UGT1A1 guided cancer therapy: Review of the evidence and considerations for clinical implementation. Cancers (Basel) 2021;13(7):1566. Abstract

Pérez-García JM et al. Prevention of sacituzumab govitecan (SG)-related neutropenia and diarrhea in patients (pts) with triple-negative or HR+/HER2- advanced breast cancer (ABC; PRIMED): A phase 2 trial. ASCO 2024;Abstract 1101.

Pistilli B et al. Datopotamab deruxtecan (Dato-DXd) vs chemotherapy (CT) in previously-treated inoperable or metastatic hormone receptor-positive, HER2-negative (HR+/HER2–) breast cancer (BC): Final overall survival (OS) from the phase III TROPION-Breast01 trial. ESMO 2025;VP1-2025.

Rugo HS et al. Overall survival with sacituzumab govitecan in hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer (TROPiCS-02): A randomised, open-label, multicentre, phase 3 trial. Lancet 2023;402(10411):1423-33. Abstract

Rugo HS et al. Health-related quality of life (HRQoL) in the phase III TROPiCS-02 trial of sacituzumab govitecan (SG) vs chemotherapy in HR+/HER2- metastatic breast cancer (MBC). ESMO 2022;Abstract 1553O. 

Rugo HS et al. Sacituzumab govitecan in hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol 2022;40(29):3365-76. Abstract

Rugo HS et al. Sacituzumab govitecan (SG) vs treatment of physician’s choice (TPC): Efficacy by Trop-2 expression in the TROPiCS-02 study of patients (pts) with HR+/HER2– metastatic breast cancer (mBC). San Antonio Breast Cancer Symposium 2022;Abstract GS1-11.

Rugo HS et al. Safety analyses from the phase 3 ASCENT trial of sacituzumab govitecan in metastatic triple-negative breast cancer. NPJ Breast Cancer 2022;8(1):98. Abstract

Tolaney SM et al. Final overall survival (OS) analysis from the phase 3 TROPiCS-02 study of sacituzumab govitecan (SG) in patients (pts) with hormone receptor–positive/HER2-negative (HR+/HER2–) metastatic breast cancer (mBC). ASCO 2023;Abstract 1003. 

 

Prof Dent

Bardia A et al. Datopotamab deruxtecan in advanced or metastatic HR+/HER2- and triple-negative breast cancer: Results from the phase I TROPION-PanTumor01 study. J Clin Oncol 2024;42(19):2281-94. Abstract

Bardia A et al. Sacituzumab govitecan in metastatic triple-negative breast cancer. N Engl J Med 2021;384(16):1529-41. Abstract

Binghe Xu et al. Sacituzumab tirumotecan (SKB264/MK-2870) in patients (pts) with previously treated locally recurrent or metastatic triple-negative breast cancer (TNBC): Results from the phase III OptiTROP-Breast01 study. ASCO 2024;Abstract 104.

Cortes J et al. Pembrolizumab plus chemotherapy in advanced triple-negative breast cancer. N Engl J Med 2022;387(3):217-26. Abstract

Dent R et al. IMpassion132 double-blind randomised phase III trial of chemotherapy with or without atezolizumab for early relapsing unresectable locally advanced or metastatic triple-negative breast cancer. Ann Oncol 2024;35(7):630-42. Abstract

Giordano A et al. Enfortumab vedotin (EV) in triple-negative breast cancer (TNBC) and HR+/HER2- breast cancer (BC) cohorts of EV-202. ASCO 2024;Abstract 1005.

Krop IE et al. Results from the phase 1/2 study of patritumab deruxtecan, a HER3-directed antibody-drug conjugate (ADC), in patients with HER3-expressing metastatic breast cancer (MBC). ASCO 2022;Abstract 1002.

Litton JK et al. Talazoparib versus chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer: Final overall survival results from the EMBRACA trial. Ann Oncol 2020;31(11):1526-35. Abstract

Litton JK et al. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N Engl J Med 2018;379(8):753-63. Abstract

Robson ME et al. OlympiAD extended follow-up for overall survival and safety: Olaparib versus chemotherapy treatment of physician’s choice in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer. Eur J Cancer 2023;184:39-47. Abstract

Robson M et al. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med 2017;377(6):523-33. Abstract

Tolaney S et al. Sacituzumab govitecan (SG) + pembrolizumab (pembro) vs chemotherapy (chemo) + pembro in previously untreated PD-L1–positive advanced triple-negative breast cancer (TNBC): Primary results from the randomized phase 3 ASCENT-04/KEYNOTE-D19 study. ASCO 2025;Abstract LBA109.

Tung N et al. TBCRC 031: Randomized phase II study of neoadjuvant cisplatin versus doxorubicin-cyclophosphamide in germline BRCA carriers with HER2-negative breast cancer (the INFORM trial). J Clin Oncol 2020;38(14):1539-48. Abstract

Yin Y et al. Sacituzumab tirumotecan in previously treated metastatic triple-negative breast cancer: a randomized phase 3 trial. Nat Med 2025;[Online ahead of print]. Abstract