Expression of forkhead-box protein A1 (FOXA1) as a significant prognostic and predictive marker for ER-positive breast cancer.

Abstract

608 Background: One of the major issues associated with the breast cancer therapy is how to determine the indication of adjuvant chemotherapy for the patients with luminal subtypes. Multigene prognosis assays such as Oncotype Dx are excellent techniques, however, there are some limitations in their clinical use, high cost and patent problems. The transcription factor network composed of ER, Forkhead-box protein A1 (FOXA1), and GATA-binding protein 3 (GATA3) is necessary for the ERα functional signature specific to luminal type, and the presence of an intact GATA-3/FOXA1/ ER network appears to be critical for the hormone responsive phenotype. This study evaluated the usefulness of the expression of FOXA1 as a prognostic and predictive marker for ER-positive breast cancer. Methods: We analyzed the expression of FOXA1, GATA3 by immunohistochemical analyses in 155 cases of primary breast cancer. We evaluated the association of the expression of these proteins with clinicopathologic characteristics and prognosis, especially in ER-positive cases. Results: (1) FOXA1 and GATA3 expressions correlated positively (p < 0.0001). (2) FOXA1 expression was positively correlated with ER (p < 0.0001) and PR (p = 0.0003), and inversely correlated with nuclear grade (p = 0.0004) and Ki 67 index (p < 0.0001). (3) FOXA1 expression was significantly correlated with the better prognosis in all (p = 0.0104) and in ER-positive cases (p = 0.0031), but no relationship in ER-negative cases. In addition, low FOXA1 expression was significantly associated with the shorter disease-free survival in patients who received adjuvant endocrine therapy (p = 0.0105). On the other hand, Ki-67 index was associated with the poor prognosis, especially in ER-negative cases, not in ER-positive cases. Conclusions: FOXA1 expression is significantly associated with the good prognosis, especially in ER-positive breast cancer. This study suggests that FOXA1 expression may be used as a prognostic and predictive marker for ER-positive breast cancer, which can be used as a more cost-effective strategy to select the patients in whom chemotherapy may be omitted. No significant financial relationships to disclose.