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<p>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; <i>P</i> = 0.016), but not in the chemotherapy-only arm (OR:1.37; <i>P</i> = 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月29日

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

摘要

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.