Breast Cancer Research and Treatment

, Volume 153, Issue 2, pp 465–474 | Cite as

FOXA2 mRNA expression is associated with relapse in patients with Triple-Negative/Basal-like breast carcinoma

  • Ariadna Perez-Balaguer
  • Fernando Ortiz-Martínez
  • Araceli García-Martínez
  • Critina Pomares-Navarro
  • Enrique Lerma
  • Gloria Peiró
Brief Report


The FOXA family of transcription factors regulates chromatin structure and gene expression especially during embryonic development. In normal breast tissue FOXA1 acts throughout mammary development; whereas in breast carcinoma its expression promotes luminal phenotype and correlates with good prognosis. However, the role of FOXA2 has not been previously studied in breast cancer. Our purpose was to analyze the expression of FOXA2 in breast cancer cells, to explore its role in breast cancer stem cells, and to correlate its mRNA expression with clinicopathological features and outcome in a series of patients diagnosed with breast carcinoma. We analyzed FOXA2 mRNA expression in a retrospective cohort of 230 breast cancer patients and in cell lines. We also knocked down FOXA2 mRNA expression by siRNA to determine the impact on cell proliferation and mammospheres formation using a cancer stem cells culture assay. In vitro studies demonstrated higher FOXA2 mRNA expression in Triple-Negative/Basal-like cells. Further, when it was knocked down, cells decreased proliferation and its capability of forming mammospheres. Similarly, FOXA2 mRNA expression was detected in 10 % (23/230) of the tumors, especially in Triple-Negative/Basal-like phenotype (p < 0.001, Fisher’s test). Patients whose tumors expressed FOXA2 had increased relapses (59 vs. 79 %, p = 0.024, log-rank test) that revealed an independent prognostic value (HR = 3.29, C.I.95 % = 1.45–7.45, p = 0.004, Cox regression). Our results suggest that FOXA2 promotes cell proliferation, maintains cancer stem cells, favors the development of Triple-Negative/Basal-like tumors, and is associated with increase relapses.


Breast carcinoma Cancer stem cells FOXA2 Prognosis 





Cancer stem cell


Disease-free survival


Epidermal growth factor receptor


Formalin-fixed paraffin-embedded


Hormonal receptor




Overall survival


Quantitative real-time PCR



We thank Mrs Doreen Dennecker for the revision of this manuscript, and Laura Andreu for their technical assistance.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10549_2015_3553_MOESM1_ESM.docx (575 kb)
Supplementary material 1 (DOCX 574 kb)


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Ariadna Perez-Balaguer
    • 1
    • 4
  • Fernando Ortiz-Martínez
    • 1
  • Araceli García-Martínez
    • 1
  • Critina Pomares-Navarro
    • 1
  • Enrique Lerma
    • 2
  • Gloria Peiró
    • 1
    • 3
  1. 1.Research UnitHospital General Universitari d’AlacantAlacantSpain
  2. 2.Department of PathologyHospital de la Santa Creu i Sant PauBarcelonaSpain
  3. 3.Pathology DepartmentUniversity General Hospital of AlicanteAlicanteSpain
  4. 4.Institute of Bioengineering of CataloniaBarcelonaSpain

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