Breastfeeding shapes a unique tumor-immune landscape in pregnancy-associated breast cancer from GEICAM-EMBARCAM study
4 affiliations
- 1Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)-Hospital Universitario Reina Sofia, Universidad de Córdoba
- 2GEICAM, Spanish Breast Cancer Group
- 3Medicine Department, Hospital Clínico Universitario de Valencia, Instituto de Investigación Sanitaria (INCLIVA), Universidad de Valencia
- 4Centro de Supercomputación y Bioinformática (SCBI), Unidad de Bioinformática, Universidad de Malaga
Abstract
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.
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BibTeX
@article{penaenriquez2026breastfeeding,
title = {{Breastfeeding shapes a unique tumor-immune landscape in pregnancy-associated breast cancer from GEICAM-EMBARCAM study}},
author = {Regina Peña-Enríquez and Ángel Guerrero-Zotano and Begoña Bermejo and Alejandra Díaz-Chacon and Yolanda Jerez Gilarranz and Jose J. Ponce Lorenzo and Juan Miguel Cejalvo and Ana Santaballa Bertran and Elena Galve-Calvo and Antonio Fernández Aramburo and Blanca Cantos Sánchez de Ibargüen and Antonio Anton-Torres and Fernando Moreno and María Helena Lopez-Ceballos and Yolanda Fernández and Susana De La Cruz and María Eva Pérez and Isabel Blancas and María Vidal-Losada and Manuel Ruiz-Borrego and Álvaro Jiménez-Arranz and David Ponferrada and Rocío Bautista-Moreno and Ana Martínez-López and María López-Herrero and Aurora Rivas-Crespo and Raul Rincón and Rosalía Caballero and Miguel Martín and Silvia Guil-Luna and Juan de la Haba-Rodríguez},
journal = {Breast Cancer Research},
year = {2026},
month = jun,
doi = {10.1186/s13058-026-02330-8},
url = {https://doi.org/10.1186/s13058-026-02330-8},
note = {CC BY},
}
RIS
TY - JOUR
TI - Breastfeeding shapes a unique tumor-immune landscape in pregnancy-associated breast cancer from GEICAM-EMBARCAM study
AU - Regina Peña-Enríquez
AU - Ángel Guerrero-Zotano
AU - Begoña Bermejo
AU - Alejandra Díaz-Chacon
AU - Yolanda Jerez Gilarranz
AU - Jose J. Ponce Lorenzo
AU - Juan Miguel Cejalvo
AU - Ana Santaballa Bertran
AU - Elena Galve-Calvo
AU - Antonio Fernández Aramburo
AU - Blanca Cantos Sánchez de Ibargüen
AU - Antonio Anton-Torres
AU - Fernando Moreno
AU - María Helena Lopez-Ceballos
AU - Yolanda Fernández
AU - Susana De La Cruz
AU - María Eva Pérez
AU - Isabel Blancas
AU - María Vidal-Losada
AU - Manuel Ruiz-Borrego
AU - Álvaro Jiménez-Arranz
AU - David Ponferrada
AU - Rocío Bautista-Moreno
AU - Ana Martínez-López
AU - María López-Herrero
AU - Aurora Rivas-Crespo
AU - Raul Rincón
AU - Rosalía Caballero
AU - Miguel Martín
AU - Silvia Guil-Luna
AU - Juan de la Haba-Rodríguez
PY - 2026
DA - 2026/06/01
JO - Breast Cancer Research
DO - 10.1186/s13058-026-02330-8
UR - https://doi.org/10.1186/s13058-026-02330-8
AB - 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.
SN - 1465-542X
SN - 1465-5411
ER -