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FOXA1 expression in breast cancer is associated with Luminal subtype and good prognosis.
  1. Mangesh A Thorat (thoratmangesh{at}gmail.com)
  1. Dept. of Pathology & Laboratory Medicine, IU School of Medicine, United States
    1. Caterina Marchio (caterina.marchio{at}icr.ac.uk)
    1. The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, United Kingdom
      1. Akira Morimiya (amorimiy{at}iupui.edu)
      1. Dept. of Pathology & Laboratory Medicine, IU School of Medicine, United States
        1. Kay Savage (kay.savage{at}icr.ac.uk)
        1. The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, United Kingdom
          1. Harikrishna Nakshatri (hnakshat{at}iupui.edu)
          1. Dept. of Surgery, IU School of Medicine, United States
            1. Jorge S Reis-Filho (jorge.reis-filho{at}icr.ac.uk)
            1. The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, United Kingdom
              1. Sunil Badve (sbadve{at}iupui.edu)
              1. Dept. of Pathology & Laboratory Medicine, IU School of Medicine, United States

                Abstract

                Purpose: FOXA1 is a forkhead family transcription factor expressed in breast cancer cells. It is essential for optimal expression of ~50% ofƒnER-related genes. We explored FOXA1 relationship with luminal and basal breast cancer subtypes, proliferation markers and survival in breast cancer patients who had received similar treatment. Materials and Methods: A tissue microarray comprising tumours from 245 invasive breast cancer patients with 67 months of median follow-up was analyzed for FOXA1 expression by immunohistochemistry. Interpretable FOXA1 expression, obtained in 184 patients, was analyzed along with other variables like tumour grade, size, nodal status, ER, PR, HER2/neu, proliferation and basal markers. Results: FOXA1 expression (score >3) was seen in 139/184 breast cancers. It correlated positively with ERƒÑ (p<0.0001), PR (p<0.0001), and luminal subtype (p<0.0001); negatively with basal subtype (p<0.0001), proliferation markers and high histological grade (p=0.0327). Univariate analysis showed nodal status, tumour grade, ER, PR, FOXA1, basal markers and p53 as significant predictors of overall survival (OS). Multivariate analysis showed only nodal status (p=0.0006) and ER (p=0.0017) to be the significant predictors of OS. In luminal subtype patient subgroup, FOXA1 expression was associated with better survival (p=0.0284) on univariate analysis. Conclusion: Based on this study in patients treated surgery followed by adjuvant anthracycline-based chemotherapy, FOXA1 expression is associated with good prognosis. It correlates with luminal subtype breast cancer, and could possibly serve as a clinical marker for luminal subtype-A. Prognostic ability of FOXA1 in these low-risk breast cancers may prove to be useful in treatment decision making.

                • Breast Cancer
                • FOXA1
                • Luminal type
                • Oestrogen receptor
                • Prognosis

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