No evidence of disease versus residual disease in long-term responders to first-line her2-targeted therapy for metastatic breast cancer

ABSTRACT BACKGROUND Long-term response to HER2-targeted therapies is infrequent in metastatic breast cancer (MBC). We evaluated clinical characteristics of HER2-positive MBC patients with no

evidence of disease (NED) vs residual disease (RES) experiencing long-term response to first-line HER2-targeted therapy. METHODS Patients receiving first-line chemotherapy-trastuzumab (CT)

or taxane-trastuzumab-pertuzumab (THP) with response duration ≥2-fold higher than in phase II/III trials (CT [18.2 months]; THP [40.4 months]) were included. Clinical characteristics and

radiographic review for NED or RES was evaluated by Cox-regression (hazard ratio; HR) or Kaplan–Meier (log-rank). Characteristics associated with NED were evaluated by logistic regression

(Odds; OR). RESULTS From 01/2005-01/2016, _N_ = 103 (4.6%) patients were identified. In multivariate analyses, NED (_N_ = 46) showed improved progression-free (PFS) and overall survival (OS)

[_p_ < 0.001] versus RES (_N_ = 57), with high 5-year PFS/OS for NED (93.2%/97.4%) relative to RES (10.6%/61.3%). Premenopausal status (_p_ = 0.006), de-novo metastases (_p_ = 0.002),

and no palliative radiotherapy (_p_ = 0.01) were associated with NED. Overall, 6/7 (85.7%) patients with NED were alive and disease-free after discontinuing HER2 treatment (≥1 year) versus

1/17 (5.9%) with RES. CONCLUSIONS Long-term responders with NED have better survival compared to RES. Premenopausal status and de novo metastatic disease are associated with NED. Prospective

studies of HER2 therapy discontinuation with NED in MBC are warranted. Access through your institution Buy or subscribe This is a preview of subscription content, access via your

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CHEMOTHERAPY IN CT1-T2/N0 HER2+ BREAST CANCER Article Open access 12 May 2022 SHORTER DURATION OF FIRST-LINE CHEMOTHERAPY REFLECTS POORER OUTCOMES IN PATIENTS WITH HER2-NEGATIVE ADVANCED

BREAST CANCER: A MULTICENTER RETROSPECTIVE STUDY Article Open access 02 November 2021 HER2DX _ERBB2_ MRNA SCORE IN FIRST-LINE ADVANCED HER2-POSITIVE BREAST CANCER TREATED WITH CHEMOTHERAPY,

TRASTUZUMAB, AND PERTUZUMAB Article Open access 25 April 2025 DATA AVAILABILITY The data that support the findings of this study are available upon request from the corresponding author. The

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directions. Cancer Treat Rev. 2014;40:276–84. https://doi.org/10.1016/j.ctrv.2013.09.001. Article  CAS  PubMed  Google Scholar  Download references ACKNOWLEDGEMENTS Princess Margaret Cancer

Centre and Cancer Care Alberta would like to acknowledge the patients and families for their contribution to this research. This study was presented at the American Society of Clinical

Oncology (ASCO) annual meeting in Chicago, USA, in June 2019. FUNDING No funding was procured for this study. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Medical Oncology and

Hematology, St Michael’s Hospital, Toronto, ON, Canada Zachary Veitch * Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada Zachary Veitch, 

Philippe L. Bedard & David W. Cescon * Medical Oncology Department, Institute of Oncology Ljubljana, Ljubljana, Slovenia Domen Ribnikar * Cancer Care Alberta, Alberta Health Services,

Calgary, AB, Canada Derek Tilley * Department of Medical Oncology, Tom Baker Cancer Centre, Calgary, AB, Canada Patricia A. Tang & Sasha Lupichuk * Department of Medical Oncology, Cross

Cancer Institute, University of Alberta, Edmonton, AB, Canada Karen King Authors * Zachary Veitch View author publications You can also search for this author inPubMed Google Scholar * Domen

Ribnikar View author publications You can also search for this author inPubMed Google Scholar * Derek Tilley View author publications You can also search for this author inPubMed Google

Scholar * Patricia A. Tang View author publications You can also search for this author inPubMed Google Scholar * Karen King View author publications You can also search for this author

inPubMed Google Scholar * Philippe L. Bedard View author publications You can also search for this author inPubMed Google Scholar * Sasha Lupichuk View author publications You can also

search for this author inPubMed Google Scholar * David W. Cescon View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS Conceptualisation—ZWV,

PAT, DR, KK, SL and DC. Data curation—ZWV, SL, KK and DR. Formal analyses—ZWV and DT. Funding acquisition—None. Investigation—ZWV and DR, Methodology—ZWV, PAT and SL. Project

administration—ZWV, DWC and PLB. Resources—ZWV, DT and DWC. Software—ZWV and DT. Supervision—SL and DWC. Validation—Not applicable. Visualisation—ZWV. Writing—Original draft—ZWV.

Writing—Review and editing—ZWV, DR, DT, PAT, KK, PLB, SL and DWC. CORRESPONDING AUTHOR Correspondence to Zachary Veitch. ETHICS DECLARATIONS ETHICS APPROVAL AND CONSENT TO PARTICIPATE This

study was approved by the Princess Margaret Cancer Centre Research Ethics Board (NCT03740503) and the Health and Research Ethics Board of Alberta (Cancer Committee). CONSENT TO PUBLISH Not

applicable. COMPETING INTERESTS ZWV has received honoraria from Pfizer, Exact Sciences, Knight Pharmaceuticals, and Novartis. DWC reports consultancy and advisory fees from AstraZeneca,

Exact Sciences, Gilead, GlaxoSmithKline, Merck, Novartis, Pfizer, and Roche; research funding to their institution from GlaxoSmithKline, Inivata, Merck, Pfizer and Roche; is a member of a

trial steering committee for Merck; and holds a patent (US62/675,228) for methods of treating cancers characterised by a high expression level of spindle and kinetochore associated complex

subunit 3 (ska3) gene. PLB has received research funding from Bristol-Myers Squibb, Sanofi, AstraZeneca, Genentech/Roche, SERVIER, GlaxoSmithKline, Novartis, SignalChem, PTC Therapeutics,

Nektar, Merck, Seattle Genetics, Mersana, Immunomedics, Eli-Lilly, Zymeworks, and VelosBio. Uncompensated advisory for Lilly, Seagen, Merck, Genentech/Roche, Bristol-Myers Squibb, and

Gilead. PAT has honoraria from Teva, Eisai, Pfizer, Novartis, Bristol-Myers Squibb, Merck, AstraZeneca and Roche. No conflicts of interest: The following authors have declared no conflicts

of interest: DR, DT, KK and SL. ADDITIONAL INFORMATION PUBLISHER’S NOTE Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

SUPPLEMENTARY INFORMATION SUPPLEMENT REPRODUCIBILITY CHECKLIST STROBE CHECKLIST RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Veitch, Z., Ribnikar,

D., Tilley, D. _et al._ No evidence of disease versus residual disease in long-term responders to first-line HER2-targeted therapy for metastatic breast cancer. _Br J Cancer_ 126, 881–888

(2022). https://doi.org/10.1038/s41416-021-01676-4 Download citation * Received: 22 October 2021 * Revised: 27 November 2021 * Accepted: 10 December 2021 * Published: 20 December 2021 *

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