Impact of GATA-3 and FOXA1 expression in patients with hormone receptor-positive/HER2-negative breast cancer

Background: Determining the indications for adjuvant chemotherapy (CT) in patients with hormone receptor (HR)-positive/HER2-negative breast cancer are difficult. The transcription factors GATA-binding protein 3 (GATA-3) and Forkhead-box protein A1 (FOXA1) are crucial for the hormone responsive phenotype of breast cancer. This study evaluated whether the expression of GATA-3 and FOXA1 is a prognostic and predictive marker of outcomes in patients with HR-positive/HER2-negative breast cancer. Methods: The expression of GATA-3 and FOXA1 was analyzed immunohistochemically in 214 patients with invasive breast cancer to evaluate the association with the clinicopathological features and the prognosis. Results: GATA-3 expression was positively correlated with FOXA1 expression (P < 0.0001). Both GATA-3 and FOXA1 were positively correlated with ER (P < 0.0001 each) and PR expression (P = 0.0001 and P = 0.0009, respectively), and inversely correlated with nuclear grade (P = 0.0002 and P = 0.0018, respectively) and Ki67 index (P = 0.0052 and P = 0.0049, respectively). Expression of GATA-3 and FOXA1 was associated with better prognosis. FOXA1 was an independent favorable prognostic marker in HR-positive/HER2-negative breast cancer. Disease-free survival rates were similar in patients with HR-positive/HER2-negative breast cancer and high FOXA1 expression given adjuvant hormone therapy (HT) alone and those given CT plus HT. Conclusion: GATA-3 and FOXA1 are associated with a less aggressive phenotype and a better prognosis in patients with HR-positive/HER2-negative breast cancer. FOXA1 may be useful in identifying those patients who may not require adjuvant CT.