Background: The assessment of the needs of the adjuvant chemotherapy has been the important problem in luminal type breast cancers. Multigene prognosis assays such as Oncotype Dx and Mammaprint, turned out to be efficient techniques. However, these assays are expensive and have not been prospectively validated. The transcription factors GATA-binding protein 3 (GATA-3) and Forkhead-box protein A1 (FOXA1) function with estrogen receptor α (ERα) in mammary morphogenesis. These transcription factors form an autoregulatory hormonal network that influences estrogen responsiveness and sensitivity to hormonal therapy. Methods: We analyzed GATA-3 and FOXA1 expression in 307 primary breast cancers by immunohistochemistry, to evaluate the association with breast cancer molecular markers, clinicopathological features and patients’ recurrence-free survival. We classified the cases into luminal A and B using hormonal receptors, HER2 and Ki67 index (cut-off value: 14%). Results: 1.GATA-3 expression was positively correlated with FOXA1 (p<0.0001). 2. GATA-3 and FOXA1 were positively correlated with ER and PgR (both p<0.0001), and inversely correlated with nuclear grade (both p<0.0001) and Ki 67 index (p=0.0003 and p<0.0001). 3. GATA-3 expression was correlated with better prognosis in luminal B cases (p=0.0013), but no relationship was found in luminal A cases. Whereas, FOXA1 was correlated with better prognosis in both luminal A (p=0.0010) and B cases (P=0.0005). Besides, FOXA1 expression influenced prognosis in the cases with high GATA-3 expression in both luminal A (p=0.0011) and B (p=0.0202) cases who received hormonal therapy, whereas GATA-3 expression had no influence on prognosis in the cases with high FOXA1 expression. 4. High FOXA1 expression was also an independent favorable prognostic factor by multivariate analysis in not only all cases but also luminal type cases. GATA-3 was not recognized as an independent prognostic factor in either case. Conclusions: Our study suggests that GATA-3 and FOXA1 are associated with hormonal sensitivity and prognosis. These data also demonstrates that the expression of FOXA1 can be more useful than GATA-3 as a biomarker in luminal type cases.