Time-varying effects of FOXA1 on breast cancer prognosis

Abstract

Results of previous studies on the associations between Forkhead box A1 (FOXA1) expression in breast cancer tissues and the prognosis varied depending on the follow-up durations. The present study would investigate whether there is a time-varying effect of FOXA1 in breast cancer tissues on the prognosis. FOXA1 expressions were evaluated in 1041 primary invasive breast tumors with tissue microarrays by immunohistochemistry. Cox models with restricted cubic splines and Kaplan-Meier survival analysis were used to examine the associations between FOXA1 and the prognosis. Flexible parametric models were applied to explore the time-varying effect of FOXA1. Overall, the association between FOXA1 expression and the prognosis was not significant but varied on the time of follow-up. Compared to FOXA1 ≤ 270 of H-score, the hazard ratios (HRs) of death for those with 271-285 of FOXA1 expression increased from 0.35 (95% CI 0.14-0.86) at 6months after diagnosis to 2.88 (95% CI 1.35-6.15) at 120months with a crossover at around 36months. Similar patterns were also observed for FOXA1 > 285 of H-score and for progression free survival (PFS). Moreover, when allowed both FOXA1 and estrogen receptor (ER) to change over time in the model (considering that ER had a similar time-varying effect), these time-varying effects remained for FOXA1 on both overall survival (OS) (P < 0.01) and PFS (P = 0.01) but were attenuated for ER (P = 0.13 for OS). This study revealed an independent time-varying effect of FOXA1 on breast cancer prognosis, which would provide an insight into the roles of FOXA1 as a marker of breast cancer prognosis and may help optimize the medication strategies.