Prognostic value of androgen receptor and FOXA1 co-expression in non-metastatic triple negative breast cancer and correlation with other biomarkers
Menée à partir d'échantillons tumoraux prélevés sur 333 patientes atteintes d'un cancer du sein triplement négatif et non métastatique (durée médiane de suivi : 7,8 ans), cette étude française évalue l'association entre la co-expression du récepteur androgénique et du facteur de transcription FOXA1 et la survie sans récidive ou la survie globale, puis analyse la corrélation entre cette co-expression et d'autres biomarqueurs (infiltration des lymphocytes dans la tumeur, expression de PD-L1, taux de mutations du gène PIK3CA, présence d'un gène PTEN défectueux et niveau de méthylation du promoteur BRCA1)
Background : In luminal androgen receptor (AR) tumours, FOXA1 may direct AR to sites occupied by ER in luminal tumours, thus stimulating proliferation.
Methods : AR 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.
Results : AR + /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).
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.
British Journal of Cancer , résumé, 2018