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FOXA1 Expression in Breast Cancer—Correlation with Luminal Subtype A and Survival

Authors' Affiliations: Departments of ¹ Pathology and Laboratory Medicine, ² Internal Medicine, ³ Surgery, and ⁴ Biochemistry and Molecular Biology; ⁵ Walther Oncology Center, Indiana University School of Medicine; ⁶ Walther Cancer Institute, Indianapolis, Indiana; ⁷ Departments of Genetics and the Pathology and Laboratory Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; ⁸ Genetic Pathology Evaluation Centre and ⁹ Child and Family Research Institute, University of British Columbia, British Columbia, Vancouver, Canada

Requests for reprints: Harikrishna Nakshatri, R4-202, Indiana Cancer Research Institute, 1044 West Walnut Street, Indianapolis, IN 46202 and Sunil Badve, Department of Pathology, Indiana University School of Medicine, 635 Barnhill Drive, MS-A128, Indianapolis, IN 46202. Phone: 317-274-2053; Fax: 1-317-278-2018; E-mail: sbadve{at}iupui.edu.

Purpose: FOXA1, a forkhead family transcription factor, is essential for optimum expression of 50% of estrogen receptor (ER):estrogen responsive genes. FOXA1 is expressed in breast cancer cells. It segregates with genes that characterize the luminal subtypes in DNA microarray analyses. The utility of FOXA1 as a possible independent prognostic factor has not been determined in breast cancers.

Materials and Methods: A tissue microarray comprising tumors from 438 patients with 15.4 years median follow-up was analyzed for FOXA1 expression by immunohistochemistry. Interpretable FOXA1 expression obtained in 404 patients was analyzed along with other prognostic factors like tumor grade, size, nodal status, ER, progesterone receptor (PR), and HER2/neu.

Results: FOXA1 expression (score >3) was seen in 300 of 404 breast cancers and it correlated with ER (P = 0.000001), PR (P = 0.00001), and luminal A subtype (P = 0.000001). Loss of expression was noted with worsening tumor grade (P = 0.001). Univariate analysis showed nodal status (P = 0.0000012), tumor size (P = 0.00001), FOXA1 (P = 0.0004), and ER (P = 0.012) to be predictors of breast cancer–specific survival. Multivariate analysis showed only nodal status (P = 0.001) and tumor size (P = 0.039) to be significant prognostic factors, whereas FOXA1 (P = 0.060) and ER (P = 0.131) were not significant. In luminal subtype A patient subgroup, FOXA1 expression was associated with better cancer-specific survival (P = 0.024) and in ER-positive subgroup, it was better predictor of cancer-specific survival (P = 0.009) than PR (P = 0.213).

Conclusion: FOXA1 expression correlates with luminal subtype A breast cancer and it is significant predictor of cancer-specific survival in patients with ER-positive tumors. Prognostic ability of FOXA1 in these low-risk breast cancers may prove to be useful in clinical treatment decisions.

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