Clinical features associated with exceptional response on first-line anti-HER2-based therapy for metastatic breast cancer: real-world data from the ESME national cohort
Year: 2026
Type: article
Abstract: Some patients with HER2-positive metastatic breast cancer (MBC) achieve prolonged disease control with first-line anti-HER2-based therapy, but associated clinical features remain poorly characterized in real-world populations. We conducted a retrospective study using the Epidemiological Strategy and Medical Economics (ESME) MBC cohort, including 18 French comprehensive cancer centers. Women with HER2-positive MBC who initiated first-line anti-HER2-based therapy between January 2008 and December 2021 and had at least 3 years of follow-up were eligible. Exceptional responders had no documented progression within 3 years. A secondary analysis evaluated factors associated with remaining progression-free at 5 years. Multivariable logistic regression with bootstrap cross-validation was used. Among 4307 eligible patients, 1016 (23.6%) were exceptional responders. Of 765 evaluable at 5 years, 523 (68.4%) remained progression-free. Factors associated with a lower likelihood of exceptional response included hormone receptor-negative (HR-) disease, a disease-free interval of 6-24 months, ≥3 metastatic sites, visceral metastases, and central nervous system involvement. First-line treatment with chemotherapy, trastuzumab, and pertuzumab was associated with exceptional response. Among exceptional responders, HR-disease, grade III tumors and first-line chemotherapy plus trastuzumab and pertuzumab were associated with progression-free at 5-year, whereas visceral metastases were associated with lower odds. Model discrimination was moderate (AUC 0.72 and 0.64, respectively). Nearly one quarter of patients remained progression-free for at least 3 years, and more than two thirds of those evaluable remained progression-free at 5 years. Clinical variables alone had limited predictive value, supporting the need for molecular and immune biomarkers to better identify this subgroup.
Source: The Breast
Authors: Thomas Grinda, Matthieu Carton, Stefania Morganti, Audrey Mailliez, Christelle Levy, Thierry Petit, Thomas Bachelot, Monica Arnedos, Véronique Diéras, Vincent Massard, Florence Dalenc, Isabelle Desmoulins, Jean-Yves Pierga, Anthony Gonçalves, Caroline Bailleux, Jean-Sebastien Frenel, Lise Bosquet, Heather A. Parsons, William Jacot, Nancy U. Lin
Institutions: Harvard University, Institut Gustave Roussy, Dana-Farber Cancer Institute, Institut Curie, Centre Oscar Lambret, Centre François Baclesse, Institut de Cancérologie Strasbourg, Centre Léon Bérard, Institut Bergonié, Centre Eugène Marquis, Institut de Cancérologie de Lorraine, Institut universitaire du cancer de Toulouse Oncopole, Centre Georges François Leclerc, Institut Paoli-Calmettes, Centre Antoine Lacassagne, Institut de Cancérologie de l'Ouest, UniCancer Group, Inserm, Université de Montpellier, Institut de Recherche en Cancérologie de Montpellier
Language: English
Topic: HER2/EGFR in Cancer Research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,200
OpenAlex ID: W7221596744