Tumor-specific major histocompatibility-II expression predicts pathological complete response to atezolizumab combined to chemotherapy in triple-negative breast cancer

Adding immune checkpoint inhibitors to neoadjuvant chemotherapy improves outcomes in early-stage triple-negative breast cancer (TNBC), but a fraction of patients derive benefit. Tumor-specific MHC-II (tsMHC-II) expression has been shown to be a predictive biomarker of pathological complete response (pCR) to neoadjuvant chemo-immunotherapy in early-stage TNBC. We performed biomarker analysis of the phase III NeoTRIP trial where patients were randomized to neoadjuvant carboplatin and nab-paclitaxel±atezolizumab. Imaging mass cytometry was used to assess tsMHC-II expression in tumor samples. TsMHC-II positivity was predefined as ≥5% of tumor cells expressing MHC-II, and at an 80th percentile exploratory cutoff. TsMHC-II positivity was associated with a higher pCR rate in the atezolizumab arm (OR:2.58; P = 0.016), but not in the chemotherapy-only arm (OR:1.37; P = 0.34) and these results were stronger using the exploratory cutoff. TsMHC-II expression is associated with improved response to neoadjuvant chemo-immunotherapy in early TNBC and could represent a clinically useful predictive biomarker for treatment personalization.

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Publication Details

Journal
npj Breast Cancer
Published
2025-09-29
DOI
https://doi.org/10.1038/s41523-025-00828-6
Primary Topic
Cancer Immunotherapy and Biomarkers
Type
article
Field-Weighted Citation Impact
0.00

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article

Tumor-specific major histocompatibility-II expression predicts pathological complete response to atezolizumab combined to chemotherapy in triple-negative breast cancer

Luca Licata, Claudio Zamagni, Begoña Bermejo, Lajos Pusztai et al.
npj Breast Cancer
Cancer Immunotherapy and Biomarkers
article

Tumor-specific major histocompatibility-II expression predicts pathological complete response to atezolizumab combined to chemotherapy in triple-negative breast cancer

Luca Licata, Claudio Zamagni, Begoña Bermejo, Lajos Pusztai, Vladimir Semiglazov, Stefania Zambelli, Chiun‐Sheng Huang, Xiao Qian Wang, Richard Greil, Maurizio Callari, H. Raza Ali, Stefania Russo, Daniel Egle, Elena Sevillano, Giampaolo Bianchini, G Mariani, Marco Colleoni, Marc Thill, Luca Gianni, Giulia Viale, Matteo Dugo, Lucia Del Mastro, Catherine M. Kelly, Eva Ciruelos, Justin Micah Balko, Antonio Antón, G. Viale
article en

Abstract

Adding immune checkpoint inhibitors to neoadjuvant chemotherapy improves outcomes in early-stage triple-negative breast cancer (TNBC), but a fraction of patients derive benefit. Tumor-specific MHC-II (tsMHC-II) expression has been shown to be a predictive biomarker of pathological complete response (pCR) to neoadjuvant chemo-immunotherapy in early-stage TNBC. We performed biomarker analysis of the phase III NeoTRIP trial where patients were randomized to neoadjuvant carboplatin and nab-paclitaxel±atezolizumab. Imaging mass cytometry was used to assess tsMHC-II expression in tumor samples. TsMHC-II positivity was predefined as ≥5% of tumor cells expressing MHC-II, and at an 80th percentile exploratory cutoff. TsMHC-II positivity was associated with a higher pCR rate in the atezolizumab arm (OR:2.58; P = 0.016), but not in the chemotherapy-only arm (OR:1.37; P = 0.34) and these results were stronger using the exploratory cutoff. TsMHC-II expression is associated with improved response to neoadjuvant chemo-immunotherapy in early TNBC and could represent a clinically useful predictive biomarker for treatment personalization.

npj Breast CancerVol. 11(1)
Innsbruck Medical University (AT), Vita-Salute San Raffaele University (IT), Universitat de València (ES), University of Cambridge (GB), Paracelsus Medical University (AT), Instituto de Salud Carlos III (ES), Yale Cancer Center (US), Mater Misericordiae University Hospital (IE), Hospital Clínico Universitario de Valencia (ES), Fondazione Michelangelo (IT), Hospital Universitario 12 De Octubre (ES), Centre for Biomedical Network Research on Rare Diseases (ES), Institute of Oncology NN Petrov (RU), Azienda USL di Bologna (IT), HM Hospitales (ES), Ospedale Santa Maria della Misericordia di Udine (IT), National Taiwan University Hospital (TW), Instituto de Investigación Sanitaria Aragón (ES), Ospedale Policlinico San Martino (IT), Agaplesion Markus Hospital (DE), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Fondazione IRCCS Istituto Nazionale dei Tumori (IT), INCLIVA Health Research Institute (ES), Centro de Investigación Biomédica en Red de Cáncer (ES), Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele (IT), European Institute of Oncology (IT), University of Genoa (IT), Vanderbilt University Medical Center (US)
Breast Cancer Research Foundation, Associazione Italiana per la Ricerca sul Cancro
Openalex Percentile: Top 64%
Cancer Immunotherapy and Biomarkers
DOIOpen Access PDFOpenAlex
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