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Expression of the forkhead box transcription factor FOXP1 is associated with oestrogen receptor alpha, oestrogen receptor beta and improved survival in familial breast cancers
  1. M Rayoo1,
  2. M Yan1,
  3. E A Takano1,
  4. G J Bates2,
  5. P J Brown2,
  6. A H Banham2,
  7. S B Fox1
  1. 1
    Department of Pathology, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia
  2. 2
    Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, University of Oxford, Oxford, UK
  1. Correspondence to Professor S B Fox, Department of Pathology, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Victoria 3002, Australia; stephen.fox{at}petermac.org

Abstract

Background: The role of FOXP1 in sporadic breast cancers has been widely studied but its role in familial breast cancers is yet unexplored.

Aims: To investigate FOXP1 expression in different molecular subtypes of familial breast cancers and to correlate its expression with clinicopathological parameters, oestrogen receptors (ER) and survival.

Methods: Immunohistochemical staining for FOXP1 was performed in 126 familial breast carcinomas comprising 35 BRCA1, 34 BRCA2 and 57 BRCAX.

Results: Nuclear FOXP1 expression ranged from focal weak to widespread strong expression. Expression of FOXP1 was higher in familial breast cancers (54%) compared with sporadic cancers (46%) (p<0.001). There was a significant correlation between FOXP1 with ERα (p = 0.038) and ERβ (p = 0.007) in familial breast cancers. FOXP1 was more highly expressed in familial breast cancers compared with sporadic cancers for luminal (p = 0.021) and basal (p<0.001), but not HER2 and null phenotypes (both p>0.05). The absence of FOXP1 expression was associated with a shorter relapse-free (p = 0.025) and overall survival (p = 0.009) in familial breast cancer. Negativity for FOXP1 was associated with a significantly worse overall survival in BRCA2 cancers (p = 0.021) and there was a non-significant separation of the survival curves for BRCA1 cancers (p = 0.183). No differences in survival were seen for BRCAX cancers (p = 0.762).

Conclusion: Results suggest that FOXP1 demonstrates different expression patterns in familial breast cancers than sporadic tumours, even in tumours showing similar phenotypes. They also suggest a different role of FOXP1 as a tumour suppressor in familial tumours, which is unrelated to ER expression and may impact on therapeutic options.

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Footnotes

  • AHB and SBF contributed equally to this work.

  • kConFab investigators also took part in the study (kConFab, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Victoria, 3002, Australia).

  • Funding This study was partly funded by the Victorian Breast Research Consortium and the Victorian Cancer Biobank, Australia.

  • Competing interests None.

  • Ethics approval Obtained from Oxford and Peter MacCallum Cancer Centre.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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