Prognostic value of androgen receptor and FOXA1 co-expression in non-metastatic triple negative breast cancer and correlation with other biomarkers

Séverine Guiu,Joelle Simony-Lafontaine,Marian Gutowski,Céline Charon-Barra,Céline Bourgier,William Jacot,Florence Boissière,Pierre-Jean Lamy,Evelyne Crapez,Elodie Chartron,Caroline Mollevi,Gilles Romieu

doi:10.1038/s41416-018-0142-6

Abstract

BackgroundIn luminal androgen receptor (AR) tumours, FOXA1 may direct AR to sites occupied by ER in luminal tumours, thus stimulating proliferation.MethodsAR and FOXA1 expression were evaluated by immunohistochemistry in 333 non-metastatic triple-negative breast cancers (TNBC). Positivity threshold was set at ≥ 1% staining. Lymphocytic infiltration, PD-L1expression, PIK3CA mutations, PTEN defects and BRCA1 promoter methylation were assessed.ResultsAR + /FOXA1 + tumours (42.4%) were more frequently: found in older patients, lobular, of lower nuclear grade, with more frequently PIK3CA mutations; exhibited less frequently BRCA1 promoter methylation, defects of PTEN and PD-L1 expression than others. Recurrence-free and overall survivals were significantly lower for AR + /FOXA1 + TNBC (median follow-up: 7.8 years).ConclusionsAR + /FOXA1 + expression defines a luminal-like TNBC subgroup affected with a worse outcome compared to other TNBC and a higher risk of late recurrences. This subgroup appears enriched in PIK3CA mutations, suggesting a role for PI3K inhibitors in this subgroup.

Highlights

Triple negative breast cancers (TNBCs) represent 15% of all breast cancer (BC) and are defined by the lack of oestrogen receptor (ER), progesterone receptor (PR) and HER2 expression/amplification
This study aimed to evaluate in a large series of non-metastatic TNBC with a long follow-up both the profiles and the prognostic value of androgen receptor (AR)/FOXA1 co-expression and its correlation with other biomarkers like PD-L1 and PIK3CA status
There is currently no standardised assay to assess AR expression but recent data suggested that AR-targeted therapies may enhance the efficacy of chemotherapy even in TNBC with low AR expression by targeting cancer stem cell-like cells.[10]

Summary

Introduction

Triple negative breast cancers (TNBCs) represent 15% of all breast cancer (BC) and are defined by the lack of oestrogen receptor (ER), progesterone receptor (PR) and HER2 expression/amplification. This subgroup of BC is extremely heterogeneous: Lehmann et al. CONCLUSIONS: AR + /FOXA1 + expression defines a luminal-like TNBC subgroup affected with a worse outcome compared to other TNBC and a higher risk of late recurrences. This subgroup appears enriched in PIK3CA mutations, suggesting a role for PI3K inhibitors in this subgroup

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