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High FOXA1 protein expression might predict late recurrence in patients with estrogen-positive and HER2-negative breast cancer

  • Preclinical study
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Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Background

Multi-gene expression assays have been developed with the aim of predicting late recurrence in patients with estrogen receptor (ER)-positive breast cancer. However, establishment of alternative markers based on immunohistochemistry is also important for achieving practical use. Based on our previous study, forkhead box A1 (FOXA1) protein was tested as a potentially useful predictive marker for late recurrence.

Methods

117 patients with ER-positive HER2-negative invasive breast cancer who developed distant metastasis following curative surgery were retrospectively investigated. We also evaluated responsiveness to endocrine therapy according to FOXA1 expression. Furthermore, publicly available mRNA microarray data were analyzed to examine patterns of metastasis according to FOXA1 mRNA expression, employing the Kaplan–Meier plotter.

Results

High expression of FOXA1 was an independent factor predicting long disease-free survival (DFS), along with small tumor size (p = 0.010 and 0.016, respectively). Discrimination of DFS was improved by combining these two factors, i.e., patients with FOXA1-high small tumors had the longest DFS while those with FOXA1-low large tumors had the shortest DFS. Moreover, we revealed that risk of distant metastasis started to increase after the completion of adjuvant endocrine therapy in patients with FOXA1-high tumors.

Conclusion

Among patients who developed distant metastasis, those with FOXA1-high tumors had significantly longer DFS. We believe our data to raise the possibility of FOXA1 being a useful predictive marker for late recurrence and to provide new insights into the biology of FOXA1-high breast cancers.

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Acknowledgement

We sincerely appreciate Dr. Bierta Barfod for her help with the language editing.

Funding

This study was supported by the Japan Society for the Promotion of Science Grant-in-Aid for Young Scientists (Grant No. JP17K16517).

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Authors and Affiliations

  1. Department of Breast Oncology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan

    Yoshiya Horimoto, Ritsuko Sasaki, May Thinzar Hlaing, Takanori Himuro & Mitsue Saito

  2. Department of Human Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan

    Yoshiya Horimoto, Noriko Sasahara, Asumi Sakaguchi, Harumi Saeki & Atsushi Arakawa

Authors
  1. Yoshiya Horimoto
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  2. Noriko Sasahara
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  3. Ritsuko Sasaki
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  4. May Thinzar Hlaing
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  5. Asumi Sakaguchi
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  9. Mitsue Saito
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Correspondence to Yoshiya Horimoto.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the ethics committee of Juntendo University Hospital (no: 16-096) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Horimoto, Y., Sasahara, N., Sasaki, R. et al. High FOXA1 protein expression might predict late recurrence in patients with estrogen-positive and HER2-negative breast cancer. Breast Cancer Res Treat 183, 41–48 (2020). https://doi.org/10.1007/s10549-020-05751-x

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  • DOI: https://doi.org/10.1007/s10549-020-05751-x

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