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

• Review published research data supporting the use of antibody-drug conjugate (ADC) therapy alone and in combination with anti-PD-1/PD-L1 antibodies for patients with newly diagnosed triple-negative metastatic breast cancer (mBC), and use this information to make appropriate treatment recommendations.
• Evaluate published clinical research findings with TROP2-directed ADCs for relapsed/refractory hormone receptor (HR)-positive and triple-negative mBC, and optimally incorporate these agents into the care of eligible patients.
• Assess the biological rationale for the evaluation of HER2-directed ADCs for HER2-low and HER2-ultralow mBC, and identify patients for whom treatment with this approach would be appropriate.
• Discern the side effects and toxicities associated with FDA-approved ADCs employed in the care of patients with mBC, and identify strategies to manage and mitigate these complications.
• Recall ongoing trials evaluating the potential role of novel ADC-based strategies for triple-negative and HR-positive mBC, and as appropriate, counsel patients 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
Video Program: Research To Practice designates this enduring material for a maximum of 1.75 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 1.75 (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. 

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/SanAntonioADCsmBC25/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:

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

Consulting Agreements: AbbVie Inc, AstraZeneca Pharmaceuticals LP, AvenCell Europe GmbH, Bioasis Technologies Inc, Biocon, BioInvent, BioNTech SE, Bliss Biopharmaceutical (Hangzhou) Co Ltd, Boehringer Ingelheim Pharmaceuticals Inc, BridgeBio, Circle Pharma, Daiichi Sankyo Inc, Delcath Systems Inc, Ellipses Pharma, ExpreS2ion Biotechnologies, Gilead Sciences Inc, Hexagon Bio, HiberCell, Jazz Pharmaceuticals Inc, Leuko-Labs, Lilly, Menarini Group, MSD, pharmaand GmbH, Reveal Genomics, Roche Laboratories Inc, Scorpion Therapeutics, Seagen Inc, Zymeworks Inc; Contracted Research Funding to Institution: AstraZeneca Pharmaceuticals LP, Baxalta GMBH/Servier Affaires, Bayer HealthCare Pharmaceuticals, Eisai Inc, F Hoffmann-La Roche Ltd, Guardant Health, IQVIA, MSD, Pfizer Inc, PIQUR Therapeutics AG, Roche Laboratories Inc, Takeda Pharmaceuticals USA Inc; Patents: US 2019/0338368 A1, WO 2014/199294 A; Speakers Bureaus:AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, Eisai Inc, Gilead Sciences Inc, Lilly, MSD, Novartis, Pfizer Inc, Roche Laboratories Inc, Stemline Therapeutics Inc, Zuellig Pharma; Stock OPTIONS — Private Companies: MAJ3 Capital SL; 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: Leuko-Labs (stock options, relative), Queen Mary University of London.

Rita Nanda, MD
Director, Breast Oncology
Associate Professor of Medicine
Section of Hematology/Oncology
The University of Chicago
Chicago, Illinois

Advisory Committees: Arvinas, AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, Exact Sciences Corporation, GE Healthcare, Gilead Sciences Inc, Guardant Health, Lilly, Mabwell Therapeutics Inc, Merck, Moderna, Novartis, Pfizer Inc, Stemline Therapeutics Inc, Summit Therapeutics; Contracted Research: Arvinas, AstraZeneca Pharmaceuticals LP, Bristol Myers Squibb, Corcept Therapeutics Inc, Genentech, a member of the Roche Group, Gilead Sciences Inc, GSK, Merck, Novartis, OBI Pharma Inc, Pfizer Inc, Relay Therapeutics, Sun Pharma Advanced Research Company, Taiho Oncology Inc.

Professor Peter Schmid, FRCP, MD, PhD
Lead, Centre of Experimental Cancer Medicine
Barts Cancer Institute
London, United Kingdom

Advisory Committees and Consulting Agreements: AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, Boehringer Ingelheim Pharmaceuticals Inc, Celgene Corporation, Eisai Inc, Merck, Novartis, Pfizer Inc, Puma Biotechnology Inc, Roche Laboratories Inc; Contracted Research: Astellas, AstraZeneca Pharmaceuticals LP, Genentech, a member of the Roche Group, Medivation Inc, a Pfizer Company, Merck, Novartis, OncoGenex Pharmaceuticals Inc, Roche Laboratories Inc.

Priyanka Sharma, MD
Frank B Tyler Professor in Cancer Research
Division of Medical Oncology, Department of Internal Medicine
Co-Program Leader
Drug Discovery, Delivery and Experimental Therapeutics Program
The University of Kansas Cancer Center
Westwood, Kansas

Advisory Committees: AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, Gilead Sciences Inc, Menarini Group, Merck, Novartis, Pfizer Inc, Stemline Therapeutics Inc; Contracted Research: Bristol Myers Squibb, Gilead Sciences Inc, Novartis; Data and Safety Monitoring Boards/Committees: Jazz Pharmaceuticals 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 Gilead Sciences Inc and Helsinn Therapeutics (US) 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.

Prof Schmid

Cortés J et al. Primary results from ASCENT-03: A randomized phase 3 study of sacituzumab govitecan vs chemotherapy in patients with previously untreated advanced triple-negative breast cancer who are not candidates for PD-(L)1 inhibitors. ESMO 2025;Abstract LBA20.

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

Dent R 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.

Punie K et al. Patient-reported outcomes (PROs) with Sacituzumab govitecan (SG) vs chemotherapy in patients with previously untreated advanced triple-negative breast cancer (TNBC) who are not candidates for PD-(L)1 inhibitors in the phase 3 ASCENT-03 study. San Antonio Breast Cancer Symposium 2025;Abstract RF6-05.

Schmid P et al. A single-arm phase 2 study of evorpacept in combination with trastuzumab and chemotherapy in participants with HER2-positive metastatic breast cancer (mBC) (ASPEN-09-03).ESMO 2025;Abstract 623TiP.

Tolaney SM 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.

Dr Sharma

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

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.

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.

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

Pristilli 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.

Dr Nanda

Bardia A et al. Final results from the randomized phase III ASCENT clinical trial in metastatic triple-negative breast cancer and association of outcomes by human epidermal growth factor receptor 2 and trophoblast cell surface antigen 2 expression. J Clin Oncol 2024;42(15):1738-44. 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

Huppert LA et al. Multicenter retrospective cohort study of the sequential use of the antibody-drug conjugates (ADCs) trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG) in patients with HER2-low metastatic breast cancer (MBC). NPJ Breast Cancer 2025;11(1):34. Abstract

Mai N et al. Real world outcomes of sequential ADC therapy in metastatic breast cancer: Patients treated with sacituzumab govitecan and trastuzumab deruxtecan. ASCO 2024;Abstract 1085.

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

Pan Y et al. Exploring intra-tumor heterogeneity in malignant peripheral nerve sheath tumors through single-cell multi-omics. AACR 2024;Abstract 3888.

Poumeaud F et al. Efficacy of administration sequence: Sacituzumab govitecan and trastuzumab deruxtecan in HER2-low metastatic breast cancer. Br J Cancer 2024;131(4):702-8. Abstract

Tarantino P et al. Outcomes of subsequent treatment regimens after trastuzumab deruxtecan in patients with metastatic breast cancer. J Natl Cancer Inst 2025;117(11):2327-35. Abstract

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

Dr Cortés

Park YH et al. Nausea and vomiting in an evolving anticancer treatment landscape: Long-delayed and emetogenic antibody-drug conjugates. Future Oncol 2025;21(10):1261-72. Abstract

Pérez-García JM et al. Prevention of sacituzumab govitecan-related neutropenia and diarrhea in patients with HER2-negative advanced breast cancer (PRIMED): An open-label, single-arm, phase 2 trial. EClinicalMedicine 2025;85:103309. Abstract

Rugo H et al. US expert Delphi consensus on the prevention and management of stomatitis in patients treated with datopotamab deruxtecan. Support Care Cancer 2025;33(9):756. Abstract

Schmid P et al. Neoadjuvant pembrolizumab or placebo plus chemotherapy followed by adjuvant pembrolizumab or placebo for high-risk early-stage TNBC: Overall survival results from the phase III KEYNOTE-522 study. ESMO Breast Cancer Annual Congress. 2024;Abstract LBA4.

Tarantino P et al. Real-world efficacy of immediate subsequent lines of therapy after trastuzumab deruxtecan (T-DXd) in patients with metastatic breast cancer (MBC) – retrospective study from the nationwide Flatiron database. San Antonio Breast Cancer Symposium 2024;Abstract P1-08-08.

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
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 component and a post-test, 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) — 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

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

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