Abstract P3-05-06: Prognostic value of androgen receptor and FOXA1 co-expression in non-metastatic triple-negative breast cancer
Authors: Guiu S , Charon-Barra C , Mollevi C , Boissiere F , Crapez E , Chartron E , Lamy P-J , Gutowski M , Bourgier C , Romieu G , Simony-Lafontaine J , Jacot W 
Published: March 2017

Background

Androgen receptor (AR) is expressed in 8-53% of triple negative breast cancer (TNBC). Its prognostic value in this subgroup is controverted. FOXA1 is essential for expression of 50% of estrogen receptor (ER)–related genes. Microarray studies identified the subgroup of molecular apocrine or luminal androgen receptor tumors that express AR and luminal genes including FOXA1 but nor ER. Preclinical data suggested that FOXA1 may direct AR to sites normally occupied by ER in luminal tumors, inducing an estrogen-like gene program stimulating proliferation. We have already shown that TNBC with AR/FOXA1 co-expression seem to behave like luminal tumors.

We aimed at evaluating co-expression AR/FOXA1-associated profiles and its prognostic value in a large retrospective series of patients with non-metastatic TNBC with a long follow-up.

Patients and methods

AR and FOXA1 expression were evaluated by immunohistochemistry in tissue microarrays of 300 patients with non-metastatic TNBC treated in our center between 2002 and 2012. Positivity threshold was set at ≥10% staining.

Results

Median age was 57.7 years (range 28.5-98). 46.2% of tumors were classified T1 and 64% pN0. We found 83.2% of ductal carcinomas, 5% of lobular carcinomas and 11.8% of other histological types. SBR grade 1-2 represented 21.4%. A basal-like phenotype (cytokeratins 5/6 and/or EGFR+) was observed in 63.7% of cases. In 161 evaluable patients, a PIKCA mutation (exon 9 or 20) was observed in 16.2% of cases. In 124 evaluable patients, a deletion of PTEN was observed in 25% of cases. Adjuvant chemotherapy was delivered in 74.5% of patients.

37.7% of patients had AR+ tumors and 29.7% had AR+ and FOXA1+ tumors. AR+/FOXA1+ tumors were more frequently: found in older patients (p&lt;0.001), lobular (p&lt;0.001) and of lower nuclear grade (p&lt;0.001) than others TNBC. AR+/FOXA1+ tumors exhibited less frequently basal-like phenotype (45.8%) than AR+/FOXA1- (77.3%) and AR-/FOXA1- (70.1%) tumors (p&lt;0.001). AR+/FOXA1+ tumors exhibited more frequently PIK3CA mutations (35.8%) than AR+/FOXA1- (16.7%) and AR-/FOXA1- (5.9%) tumors (p&lt;0.001). AR+/FOXA1+ tumors exhibited less frequently PTEN deletion (6.8% vs 16.7% for AR+/FOXA1- vs 36.5% for AR-/FOXA1- tumors, respectively, p=0.001).

With a median follow-up of 5.5 years, recurrence-free survival (RFS) was significantly lower for patients with AR+/FOXA1+ tumors (p=0.046). 3-years RFS were 84.2% and 85.3% for AR+/FOXA1+ and the others TNBC, respectively. 5-years RFS were 67.4% and 79.4% for AR+/FOXA1+ and the others TNBC, respectively. Tumor size, nodal status and adjuvant chemotherapy were also statistically correlated to RFS. Tumor size, nodal status, histology and adjuvant chemotherapy were significantly associated with overall survival.

Conclusions

In this large series, almost 30% of TNBC had an AR/FOXA1 co-expression with distinct clinicopathological characteristics and a worse outcome than others TNBC with higher risk of late recurrences. These biomarkers could be useful to identify a subgroup of TNBC and could have therapeutic implications: anti-androgen are under investigation, FOXA1 could be another therapeutic target and PI3K inhibitors should be evaluated in this specific subgroup, alone or in association with anti-androgens.

Citation Format: Guiu S, Charon-Barra C, Mollevi C, Boissiere F, Crapez E, Chartron E, Lamy P-J, Gutowski M, Bourgier C, Romieu G, Simony-Lafontaine J, Jacot W. Prognostic value of androgen receptor and FOXA1 co-expression in non-metastatic triple-negative breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-05-06.