FOXA1 Is a Prognostic Marker in Breast Cancer – A Validation Study of 4046 Cases
R Mehta, RK Jain, TO Nielsen, S Leung, J Choo, H Nakshatri, D Hunstman, S Badve. Indiana University, Indianapolis; University of British Columbia, Vancouver, Canada
Background: Forkhead box protein A (FOXA) proteins play major roles in development and differentiation. Recently, FOXA1 has been identified to play a role in controlling nearly 50% of estrogen receptor target genes and has been deemed as a 'pioneer factor'. It has been previously demonstrated in small studies that FOXA1 is a prognostic marker that correlates with Luminal subtype A tumors. The aim of this study was to investigate the precise role of FOXA1 in breast cancer using a large population based cohort.
Design: Expression of FOXA1 was analyzed in a tissue microarray of 4,046 invasive breast cancer cases with a median follow- up of 12.4 years using immunohistochemistry. Nuclear FOXA1 expression was correlated clinico-pathologic variables using methods and cut-off points as described in literature. The entire cohort was divided into training (n=2038) and validation (n=2008) sets to avoid corrections for multiple comparisons.
Results: Variable intensity of FOXA1 expression was noted in the 3581 interpretable tumors: none (10.6%), weak (3.5%), moderate (19.3%) and strong (55.1%). High level of FOXA1 expression (score >3) was seen in 86% of the cases. FOXA1 expression correlated positively with older age, ER, PR, GATA-3, E-cadherin (each p-value < 0.0001) and negatively with tumor size, tumor grade, nodal status, Ki67, HER2 expression and basal subtype (each p-value < 0.0001). Univariate analyses showed smaller tumor size, lower grade, node negative status, absence of LVI, and expression of ER, PR, lack of HER2, and low Ki67 were independent predictors of better overall survival. Luminal A subtype cancers had best overall survival when compared to other subtypes. FOXA1 is a significant predictor of breast cancer specific survival (p=0.012) and locoregional relapse free survival (p=0.0001). It did not correlate with disease free survival (p=0.110) and distant relapse free survival (p=0.147). In those treated with tamoxifen, low FOXA1 expression was associated with poor overall survival (p<0.0001).
Conclusions: FOXA1 expression is a prognostic marker in breast cancer. More importantly, it predicts response to tamoxifen in hormone receptor positive patients.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 28, Monday Morning