• FoxM1 upregulation correlates with worse recurrence-free survival in breast cancer

      Nguyen, Tro; Nahta, Rita (2021)
      Breast cancer is the second most deadly malignancy among women in the US. Breast cancers harbor intrinsic heterogeneity, allowing stratification into molecular subtypes. Basal-like breast cancer (BLBC) is an aggressive subtype with a high rate of metastasis and poor overall survival. Due to poor understanding of the molecular drivers, few therapeutic options exist for BLBC. Studies suggest that the forkhead box M1 (FoxM1) transcription factor is upregulated in breast cancer. However, the clinical implications of FoxM1 upregulation, including in BLBC, remain unclear. The aims of this study were to (1) compare FoxM1 expression in breast cancer vs normal breast, and (2) correlate FoxM1 expression with clinical outcome using publicly accessible databases. First, we searched breast cancer datasets in Oncomine using FoxM1 as a query term. FoxM1 expression was significantly (p<0.001) higher in invasive ductal breast carcinoma vs normal breast. Next, we searched the KM Plotter breast cancer database using FoxM1 as a query. Among 4,929 patients with breast cancer, median recurrence-free survival (RFS) was significantly (p<0.001) lower in patients with high (upper quartile, 34.13 months) vs low (upper quartile, 80 months) FoxM1 expression. A sub-analysis for BLBC (n=846) demonstrated that median RFS did not significantly (p<0.053) differ in patients with high (upper quartile, 25.2 months) vs low (upper quartile, 26 months) FoxM1. These results suggest that FoxM1 is upregulated in breast cancer in association with worse clinical outcome. Future studies will examine the mechanisms through which FoxM1 is upregulated and strategies for targeting FoxM1 in breast cancer.