What Clinicians Want to Know: Addressing Community Oncologists’ Questions About the Current and Future Role of Antibody-Drug Conjugates in the Management of Breast Cancer — Symposium Proceedings

Faculty

TARGET AUDIENCE
This activity 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

• 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 current clinical role of this novel treatment approach.
• Evaluate current research evidence with HER2-directed ADC therapy for patients with HER2-positive localized breast cancer and residual disease after neoadjuvant treatment.
• Appraise available research data and relevant 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 TROP2-directed ADC therapy in combination with anti-PD-1/PD-L1 antibodies for triple-negative mBC, and use this information to make appropriate treatment recommendations.
• Evaluate published clinical research findings with TROP2-directed ADC monotherapy for HR-positive and triple-negative mBC, and optimally incorporate these agents into clinical 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 these complications.
• Recall ongoing trials evaluating the potential role of novel ADC-based strategies in the localized and metastatic settings, and appropriately counsel patients with breast cancer regarding enrollment.

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Please note, this program has been specifically designed for the following ABIM specialty: medical oncology.

AMERICAN BOARD OF SURGERY (ABS) — CONTINUOUS CERTIFICATION (CC)
Successful completion of this CME activity, 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, this program has been specifically designed for the following ABS practice area: complex general surgical oncology.

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HOW TO USE THIS CME ACTIVITY
To receive credit for this activity, 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.

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

Prof Curigliano — Advisory Committees, Consulting Agreements and Speakers Bureaus: AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, Gilead Sciences Inc, Lilly, Menarini Group, Novartis, Pfizer Inc; Data and Safety Monitoring Boards/Committees: Roche Laboratories Inc. Prof Dent — Advisory Committees and Consulting Agreements: AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, Eisai Inc, Genentech, a member of the Roche Group, Lilly, MSD, Novartis, Pfizer Inc, Roche Laboratories Inc; Contracted Research: AstraZeneca Pharmaceuticals LP, Roche Laboratories Inc. Dr Hamilton — Consulting/Advisory Roles (All Payments to Institution): Accutar Biotechnology Inc, Arvinas, AstraZeneca Pharmaceuticals LP, BeOne, Circle Pharma, Daiichi Sankyo Inc, Entos Pharmaceuticals, Genentech, a member of the Roche Group, Gilead Sciences Inc, Halda Therapeutics, Incyclix Bio, IQVIA, Janssen Biotech Inc, Jazz Pharmaceuticals Inc, Jefferies LLC, Johnson & Johnson, Lilly, Medical Pharma Services SRO, Mersana Therapeutics Inc, Novartis, Pfizer Inc, Pyxis Oncology, Samsung Bioepis, Shorla Oncology, Stemline Therapeutics Inc, Tempus, Zentalis Pharmaceuticals; Research Funding (All Payments to Institution): AbbVie Inc, Acerta Pharma — A member of the AstraZeneca Group, Accutar Biotechnology Inc, ADC Therapeutics, Akesobio Australia Pty Ltd, Amgen Inc, Aravive Inc, ARS Pharmaceuticals, Artios Pharma Limited, Arvinas, AstraZeneca Pharmaceuticals LP, AtlasMedx Inc, BeOne, Black Diamond Therapeutics Inc, Bliss Biopharmaceutical (Hangzhou) Co Ltd, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, Compugen, Context Therapeutics, Cullinan Therapeutics, Curis Inc, CytomX Therapeutics, Daiichi Sankyo Inc, Dantari, Deciphera Pharmaceuticals Inc, Duality Biologics, eFFECTOR Therapeutics Inc, Eisai Inc, Ellipses Pharma, Elucida Oncology Inc, EMD Serono Inc, Fochon Pharmaceuticals, FUJIFILM Pharmaceuticals USA Inc, G1 Therapeutics Inc, Genentech, a member of the Roche Group, Gilead Sciences Inc, Harpoon Therapeutics, Hutchison MediPharma, ImmunoGen Inc, Incyte Corporation, Infinity Pharmaceuticals Inc, Inspirna, InventisBio, Jacobio Pharmaceuticals Group Co Ltd, Karyopharm Therapeutics, K-Group Beta, Kind Pharmaceuticals LLC, Leap Therapeutics Inc, Lilly, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company, Lycera, MacroGenics Inc, Marker Therapeutics Inc, Merck, Mereo BioPharma, Mersana Therapeutics Inc, Merus, Molecular Templates, Myriad Genetic Laboratories Inc, Novartis, NuCana, Olema Oncology, Oncothyreon, ORIC Pharmaceuticals, Orinove Inc, Orum Therapeutics, Pfizer Inc, pharmaand GmbH, PharmaMar, Pieris Pharmaceuticals Inc, Pionyr Immunotherapeutics, Plexxikon Inc, Prelude Therapeutics, ProFound Therapeutics, Radius Health Inc, Regeneron Pharmaceuticals Inc, Relay Therapeutics, Repertoire Immune Medicines, Seagen Inc, Sermonix Pharmaceuticals, Shattuck Labs, Stemline Therapeutics Inc, Sutro Biopharma, Syndax Pharmaceuticals, Syros Pharmaceuticals Inc, Taiho Oncology Inc, Takeda Pharmaceuticals USA Inc, Tesaro, A GSK Company, Tolmar, Transcenta, Treadwell Therapeutics, Verastem Inc, Zenith Epigenetics, Zymeworks Inc; Nonrelevant Financial Relationships: Dana-Farber Cancer Institute. Prof Harbeck — Consulting Agreements: Exact Sciences Corporation, Sandoz Inc, a Novartis Division; Data and Safety Monitoring Boards/Committees: Gilead Sciences Inc, IQVIA, Roche Laboratories Inc; Speakers Bureaus: AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, Gilead Sciences Inc, Lilly, Menarini Group, MSD, Novartis, Pfizer Inc, Pierre Fabre, Roche Laboratories Inc, Stemline Therapeutics Inc, Viatris, Zuellig Pharma; Nonrelevant Financial Relationships: West German Study Group (WSG).

MODERATOR

Dr Rugo — 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, Merck, Stemline Therapeutics Inc; Contracted Research (Funding to Prior Institution, UCSF): Ambrx, AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, Genentech, a member of the Roche Group, Gilead Sciences Inc, Lilly, Merck, Novartis, 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.

This educational activity contains 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.

This activity is supported by educational grants from AstraZeneca Pharmaceuticals LP and Daiichi Sankyo Inc.

Release date: July 2026
Expiration date: July 2027

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

Prof Dent

Cameron DAA et al. DESTINY-Breast04 subgroup analyses of trastuzumab deruxtecan (T-DXd) vs treatment of physician’s choice (TPC) in patients (pts) with human epidermal growth factor 2 (HER2)-low, estrogen-receptor (ER) expression immunohistochemistry (IHC) 0-10% metastatic breast cancer (mBC). ESMO Breast 2023;Abstract 192MO.

Cortes JC et al. Primary results from ASCENT-03: A randomized phase III study of sacituzumab govitecan (SG) vs chemotherapy (chemo) in patients (pts) with previously untreated advanced triple-negative breast cancer (TNBC) who are unable to receive PD-(L)1 inhibitors (PD-[L]1i). 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

de Azambuja E et al. Metastatic breast cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol 2026;[Online ahead of print]. Abstract

Dent R et al. Datopotamab deruxtecan in patients with untreated, advanced triple-negative breast cancer (TROPION-Breast02): A randomised, open-label, international, phase III trial. Ann Oncol 2026;[Online ahead of print]. 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.

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):630-62. Abstract

Garrido-Castro AC et al. TROP2-directed antibody drug conjugates: New first-line treatment for all patients with advanced triple-negative breast cancer? Ann Oncol 2026;[Online ahead of print]. Abstract

Medford A et al. Antibody drug conjugates for patients with breast cancer. Curr Probl Cancer 2021;45(5):100795. Abstract

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

Schmid P et al. Datopotamab deruxtecan (Dato-DXd) in combination with durvalumab as first-line treatment for unresectable locally advanced or metastatic triple-negative breast cancer: Results from arms 7 and 8 of the phase Ib/II BEGONIA study. Ann Oncol 2026[Online ahead of print]. Abstract

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.

Zhang J et al. Pumitamig in combination with DB-1305/BNT325 as first-line (1L) treatment for patients with advanced or metastatic triple-negative breast cancer (a/mTNBC): Efficacy and safety from a multicenter, open-label, phase I/II trial. ESMO Breast 2026;Abstract 426RO.

Prof Curigliano

Bartsch R et al. Final outcome analysis from the phase II TUXEDO-1 trial of trastuzumab-deruxtecan in HER2-positive breast cancer patients with active brain metastases. Neuro Oncol 2024;26(12):2305-15. Abstract

Dieras V et al. HER2CLIMB-05: A phase III study of tucatinib versus placebo in combination with trastuzumab and pertuzumab as first-line maintenance therapy for HER2+ metastatic breast cancer. J Clin Oncol 2026;44(17):1597-607. Abstract

Hurvitz SA et al. A pooled analysis of trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-positive (HER2+) metastatic breast cancer (mBC) with brain metastases (BMs) from DESTINY-Breast (DB) -01, -02, and -03. ESMO 2023;Abstract 377O.

Lin N et al. Trastuzumab deruxtecan in patients with HER2+ advanced/metastatic breast cancer with or without brain metastases: DESTINY-Breast12 primary results. ESMO 2024;Abstract LBA18.

Metzger O et al. Palbociclib for hormone-receptor-positive, HER2-positive advanced breast cancer. N Engl J Med 2026;394(5):451-62. 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.

Swain SM et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): End-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol 2020;21(4):519-30. Abstract

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

Vaz Batista M et al. Trastuzumab deruxtecan in patients with HER2[+] or HER2-low advanced breast cancer and pathologically confirmed leptomeningeal carcinomatosis: Results from cohort 5 of the DEBBRAH study. San Antonio Breast Cancer Symposium 2023;Abstract PS11-05.

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. 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

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.

Curigliano G et al. Trastuzumab deruxtecan in hormone receptor-positive, HER2-low/-ultralow metastatic breast cancer (DESTINY-Breast06): Outcome analyses by time to progression on prior first-line endocrine therapy with CDK4/6 inhibitor and baseline burden of disease. Ann Oncol 2026;37(6):849-60. 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. A phase II study of patritumab deruxtecan (HER3-DXd) in patients (pts) with metastatic breast cancer (MBC). ESMO Breast 2026;Abstract 422RO.

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

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.

Pistilli B et al. Datopotamab deruxtecan versus chemotherapy in previously treated inoperable/metastatic hormone receptor-positive, HER2-negative breast cancer: Final overall survival analysis of the phase III TROPION-Breast01 study. Ann Oncol 2026;37(5):663-74. Abstract

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. 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. Overall survival (OS) results from the phase III TROPiCS-02 study of sacituzumab govitecan (SG) vs treatment of physician’s choice (TPC) in patients (pts) with HR+/HER2- metastatic breast cancer (mBC). ESMO 2022;Abstract LBA76.

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

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 Harbeck

Cortazar P et al. Pathological complete response and long-term clinical benefit in breast cancer: The CTNeoBC pooled analysis. Lancet 2014;384(9938):164-72. Abstract

Geyer CE et al. Trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients (pts) with high-risk human epidermal growth factor receptor 2–positive (HER2+) primary breast cancer (BC) with residual invasive disease after neoadjuvant therapy (tx): Interim analysis of DESTINY-Breast05. ESMO 2025;Abstract LBA1.

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

Harbeck N et al. DESTINY-Breast11: Neoadjuvant trastuzumab deruxtecan alone (T-DXd) or followed by paclitaxel + trastuzumab + pertuzumab (T-DXd-THP) vs SOC for high-risk HER2+ early breast cancer (eBC). ESMO 2025;Abstract 291O.

Harbeck N et al. Trofuse-032: A phase 3, randomized study of pembrolizumab plus sacituzumab tirumotecan or chemotherapy followed by pembrolizumab plus chemotherapy for early-stage triple-negative breast cancer or hormone receptor-low-positive (HR-low+)/ human epidermal growth factor receptor 2-negative (HER2−) breast cancer. San Antonio Breast Cancer Symposium 2025;Abstract PS5-12-25.

Loibl S et al. Trastuzumab deruxtecan in residual HER2-positive early breast cancer. N Engl J Med 2026;394(9):845-57. Abstract

Loibl S et al. Early breast cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol 2024;35(2):159-82. Abstract

Loibl S et al. Phase III study of adjuvant ado-trastuzumab emtansine vs trastuzumab for residual invasive HER2-positive early breast cancer after neoadjuvant chemotherapy and HER2-targeted therapy: KATHERINE final IDFS and updated OS analysis. San Antonio Breast Cancer Symposium 2023;Abstract GS03-12.

McArthur HL et al. TROPION-Breast04: A randomized phase III study of neoadjuvant datopotamab deruxtecan (Dato-DXd) plus durvalumab followed by adjuvant durvalumab versus standard of care in patients with treatment-naïve early-stage triple negative or HR-low/HER2- breast cancer. Ther Adv Med Oncol 2025;17:17588359251316176. Abstract

Dr Hamilton

Ciruelos E et al. Safety profile of trastuzumab deruxtecan in advanced breast cancer: Expert opinion on adverse event management. Clin Transl Oncol 2024;26(7):1539-48. Abstract

Kang S, Kim SB. Toxicities and management strategies of emerging antibody-drug conjugates in breast cancer. Ther Adv Med Oncol 2025;17:17588359251324889. Abstract

Meric-Bernstam F et al. Prophylaxis, clinical management, and monitoring of datopotamab deruxtecan-associated oral mucositis/stomatitis. Oncologist 2025;30(3). Abstract

Riccardi F et al. A comprehensive overview on antibody-drug conjugates: From the conceptualization to cancer therapy. Front Pharmacol 2023;14:1274088. Abstract

Rugo HS et al. Optimizing treatment management of trastuzumab deruxtecan in clinical practice of breast cancer. ESMO Open 2022;7(4):100553. Abstract

Tarantino P, Tolaney SM. Detecting and managing T-DXd-related interstitial lung disease: The five “S” rules. JCO Oncol Pract 2023;19(8):526-7. Abstract