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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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.