Risk stratification and relapse pattern in triple-negative breast cancer with pathological complete response after neoadjuvant treatment: the European GAMBIT real-world study

Pathologic complete response after neoadjuvant treatment is considered a surrogate of cure in triple-negative breast cancer, yet around 10% of patients still relapse. Whether baseline stromal tumor-infiltrating lymphocytes can stratify this residual risk is unknown. Here, we report on GAMBIT, a multicentric real-world retrospective study of 2457 patients with triple-negative breast cancer or estrogen receptor-low disease, HER2-negative, of whom 1192 obtained a pathological complete response and 690 have evaluable tumor infiltrating lymphocytes. Among patients with pathological complete response, clinical nodal status and tumor infiltrating lymphocytes are independently prognostic and patients with clinical node-positive/low-tumor infiltrating lymphocytes tumors experience substantially worse outcomes, with five-year distant relapse-free survival of 83.4% and overall survival of 85.8%. In this high-risk subgroup, five-year cumulative incidence of central nervous system reaches 7.5%, including 6.9% presenting as isolated central nervous system relapse. In this work, we identify a high-risk subgroup despite pathologic complete response and provide a framework supporting risk-adapted trial design incorporating central nervous system-directed strategies. In patients with triple-negative breast cancer (TNBC) receiving neoadjuvant therapy (NAT), achieving pathological complete response (pCR) is often considered a surrogate of a cure but around 10% go on to relapse. Here, the authors report a real-world study investigating prognostic factors of recurrence and subsequent relapse patterns in patients with TNBC who obtained pCR after NAT.

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Journal
Nature Communications
Published
2026-06-24
DOI
https://doi.org/10.1038/s41467-026-74056-2
Primary Topic
Breast Cancer Treatment Studies
Type
article
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article

Risk stratification and relapse pattern in triple-negative breast cancer with pathological complete response after neoadjuvant treatment: the European GAMBIT real-world study

Davide Massa, Martina Rotolo, Patrick Neven, Andri Papakonstantinou et al.
Nature Communications
Breast Cancer Treatment Studies
article

Risk stratification and relapse pattern in triple-negative breast cancer with pathological complete response after neoadjuvant treatment: the European GAMBIT real-world study

Davide Massa, Martina Rotolo, Patrick Neven, Andri Papakonstantinou, Claudio Vernieri, Angelo Paolo Dei Tos, Sabrina Nucera, Federica Martorana, Valentina Guarneri, Jean‐Sébastien Frenel, Alexios Matikas, Laetitia Someil, Paolo Vigneri, Hugo M. Horlings, Christine Desmedt, Giampaolo Bianchini, William Jacot, Theodoros Foukakis, Giuseppe Floris, Marleen Kok, Mario Campone, Esther H. Lips, Moira Ragazzi, Francesca Patanè, Maria Vittoria Dieci, Giorgio Bonomi, Ioannis Zerdes, Matteo Lambertini, Elisa Gasparini, Federico Piacentini, Stefania Lando, Dario Trapani, Amélie Gudin-De-Vallerin, Andrea Botticelli, Alberto Zambelli, Sylvie Giacchetti, Andrea Vingiani, Ornella Garrone, Lorenzo Nicolè, Emilio Bria
article en

Abstract

Pathologic complete response after neoadjuvant treatment is considered a surrogate of cure in triple-negative breast cancer, yet around 10% of patients still relapse. Whether baseline stromal tumor-infiltrating lymphocytes can stratify this residual risk is unknown. Here, we report on GAMBIT, a multicentric real-world retrospective study of 2457 patients with triple-negative breast cancer or estrogen receptor-low disease, HER2-negative, of whom 1192 obtained a pathological complete response and 690 have evaluable tumor infiltrating lymphocytes. Among patients with pathological complete response, clinical nodal status and tumor infiltrating lymphocytes are independently prognostic and patients with clinical node-positive/low-tumor infiltrating lymphocytes tumors experience substantially worse outcomes, with five-year distant relapse-free survival of 83.4% and overall survival of 85.8%. In this high-risk subgroup, five-year cumulative incidence of central nervous system reaches 7.5%, including 6.9% presenting as isolated central nervous system relapse. In this work, we identify a high-risk subgroup despite pathologic complete response and provide a framework supporting risk-adapted trial design incorporating central nervous system-directed strategies. In patients with triple-negative breast cancer (TNBC) receiving neoadjuvant therapy (NAT), achieving pathological complete response (pCR) is often considered a surrogate of a cure but around 10% go on to relapse. Here, the authors report a real-world study investigating prognostic factors of recurrence and subsequent relapse patterns in patients with TNBC who obtained pCR after NAT.

Nature Communications
Università Cattolica del Sacro Cuore (IT), University of Modena and Reggio Emilia (IT), Karolinska University Hospital (SE), University of Padua (IT), University of Milan (IT), Breast Cancer Research Foundation (US), Université Paris Cité (FR), Universitair Ziekenhuis Leuven (BE), Saint Louis University Hospital (US), Agostino Gemelli University Polyclinic (IT), Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT), Karolinska Institutet (SE), The Netherlands Cancer Institute (NL), University of Catania (IT), Azienda Sanitaria Unità Locale di Reggio Emilia (IT), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes Angers (FR), VIB-KU Leuven Center for Cancer Biology (BE), Assistance Publique – Hôpitaux de Paris (FR), Institut de Cancérologie de l'Ouest (FR), Ospedale Papa Giovanni XXIII (IT), Istituto Oncologico Veneto (IT), Oncode Institute (NL), IFOM (IT), IRCCS Ospedale San Raffaele (IT), Institut de Recherche en Cancérologie de Montpellier (FR), Hôpital Saint-Louis (FR), Ospedale dell' Angelo (IT), Ospedale Policlinico San Martino (IT), Azienda Ospedale - Università Padova (IT), Fondazione Humanitas per la Ricerca (IT), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Fondazione IRCCS Istituto Nazionale dei Tumori (IT), European Institute of Oncology (IT), University of Milano-Bicocca (IT), University of Genoa (IT), Sapienza University of Rome (IT), KU Leuven (BE)
Ministerie van Volksgezondheid, Welzijn en Sport, Fonds Wetenschappelijk Onderzoek, Ministero della Salute, Università degli Studi di Padova, Svenska Sällskapet för Medicinsk Forskning, Associazione Italiana per la Ricerca sul Cancro, Vlaamse regering
Good health and well-being
Openalex Percentile: Top 8%
Breast Cancer Treatment Studies
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