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Background <p>Pregnancy-associated breast cancer (PABC) is an aggressive malignancy affecting young women during gestation, lactation, or the post-weaning period. Despite its clinical significance and poor prognosis, how these physiological stages shape tumor biology remains poorly understood. Here, we integrate reproductive context with molecular and immune profiling to define shared and stage-specific features of PABC and uncover potential therapeutic vulnerabilities.</p> Methods <p>We conducted BC360 NanoString gene expression analysis and CIBERSORTx immune deconvolution in 106 breast cancer cases, including 57 PABC patients stratified by diagnosis stage (gestation, breastfeeding, or post-weaning) and 49 non-PABC controls.</p> Results <p>Our study identified a shared aggressive signature across all PABC cases, marked by increased proliferation and impaired DNA repair. Notably, breastfeeding patients (PABC-BF) emerged as a distinct subset, displaying an immune-inflamed tumor profile characterized by elevated inflammatory chemokines, enriched CD8⁺ T-cell and regulatory T-cell infiltration, and prominent TIGIT inhibitory checkpoint upregulation.</p> Conclusions <p>These findings reveal lactation as a physiological framework that shapes tumor immunity, defining a distinct tumor-immune landscape which warrants further investigation for potential therapeutic approaches.</p>

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Breastfeeding shapes a unique tumor-immune landscape in pregnancy-associated breast cancer from GEICAM-EMBARCAM study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月24日

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  • Regina Peña-Enríquez,
  • Ángel Guerrero-Zotano,
  • Begoña Bermejo,
  • Alejandra Díaz-Chacon,
  • Yolanda Jerez Gilarranz,
  • José JPonce Lorenzo,
  • Juan Miguel Cejalvo,
  • Ana Santaballa Bertran,
  • Elena Galve-Calvo,
  • Antonio Fernández Aramburo,
  • Blanca Cantos Sánchez de Ibargüen,
  • Antonio Anton-Torres,
  • Fernando Moreno,
  • María Helena Lopez-Ceballos,
  • Yolanda Fernández,
  • Susana De La Cruz,
  • María Eva Pérez,
  • Isabel Blancas,
  • María Vidal-Losada,
  • Manuel Ruiz-Borrego,
  • Álvaro Jiménez-Arranz,
  • David Ponferrada,
  • Rocío Bautista-Moreno,
  • Ana Martínez-López,
  • María López-Herrero,
  • Aurora Rivas-Crespo,
  • Raul Rincón,
  • Rosalía Caballero,
  • Miguel Martín,
  • Silvia Guil-Luna,
  • Juan de la Haba-Rodríguez

摘要

Background

Pregnancy-associated breast cancer (PABC) is an aggressive malignancy affecting young women during gestation, lactation, or the post-weaning period. Despite its clinical significance and poor prognosis, how these physiological stages shape tumor biology remains poorly understood. Here, we integrate reproductive context with molecular and immune profiling to define shared and stage-specific features of PABC and uncover potential therapeutic vulnerabilities.

Methods

We conducted BC360 NanoString gene expression analysis and CIBERSORTx immune deconvolution in 106 breast cancer cases, including 57 PABC patients stratified by diagnosis stage (gestation, breastfeeding, or post-weaning) and 49 non-PABC controls.

Results

Our study identified a shared aggressive signature across all PABC cases, marked by increased proliferation and impaired DNA repair. Notably, breastfeeding patients (PABC-BF) emerged as a distinct subset, displaying an immune-inflamed tumor profile characterized by elevated inflammatory chemokines, enriched CD8⁺ T-cell and regulatory T-cell infiltration, and prominent TIGIT inhibitory checkpoint upregulation.

Conclusions

These findings reveal lactation as a physiological framework that shapes tumor immunity, defining a distinct tumor-immune landscape which warrants further investigation for potential therapeutic approaches.