GATA3 and markers of epithelial-mesenchymal transition predict long-term benefit from tamoxifen in ER-positive breast cancer.

Autor: Sandström J; Department of Biomedical and Clinical Sciences and Department of Oncology, 581 83 Linköping University, Linköping, Sweden., Bomanson J; Department of Biomedical and Clinical Sciences and Department of Oncology, 581 83 Linköping University, Linköping, Sweden., Pérez-Tenorio G; Department of Biomedical and Clinical Sciences and Department of Oncology, 581 83 Linköping University, Linköping, Sweden., Jönsson C; Department of Biomedical and Clinical Sciences and Department of Oncology, 581 83 Linköping University, Linköping, Sweden., Nordenskjöld B; Department of Biomedical and Clinical Sciences and Department of Oncology, 581 83 Linköping University, Linköping, Sweden., Fornander T; Department of Oncology and Pathology, Karolinska Institute and University Hospital, Stockholm, Sweden., Lindström LS; Department of Oncology and Pathology, Karolinska Institute and University Hospital, Stockholm, Sweden.; Breast Center, Karolinska Comprehensive Cancer Center, Karolinska University Hospital, Stockholm, Sweden., Stål O; Department of Biomedical and Clinical Sciences and Department of Oncology, 581 83 Linköping University, Linköping, Sweden. olle.stal@liu.se.
Jazyk: angličtina
Zdroj: NPJ breast cancer [NPJ Breast Cancer] 2024 Sep 06; Vol. 10 (1), pp. 78. Date of Electronic Publication: 2024 Sep 06.
DOI: 10.1038/s41523-024-00688-6
Abstrakt: GATA binding protein 3 (GATA3) is essential for normal development of the mammary gland and associated with ER-positive breast cancer. Loss of GATA3 has been associated with epithelial-mesenchymal transition (EMT) in experimental studies. We investigated tumoral GATA3 in a cohort of postmenopausal patients with lymph-node negative breast cancer, randomized to adjuvant tamoxifen or control. Nuclear GATA3 expression was assessed with immunohistochemistry and GATA3 gene expression with Agilent microarrays. High GATA3 nuclear expression was associated with a lower rate of distant recurrence in ER-positive breast cancer (HR = 0.60, 95% CI 0.39-0.93). Low gene expression of GATA3 was associated with limited long-term benefit from adjuvant tamoxifen (interaction: p = 0.033). GATA3 gene expression was associated with the epithelial markers CDH1 (E-cadherin) and FOXA1, whereas negatively associated with several mesenchymal markers. Low expression of CDH1 was associated with marginal tamoxifen benefit (HR = 0.80 (0.43-1.49)), whereas patients with higher expression showed a significant benefit (HR = 0.33 (0.20-0.55), interaction: p = 0.029). In ER-positive breast cancer, diminished expression of GATA3 is associated with markers of EMT and poor long-term benefit from tamoxifen.
(© 2024. The Author(s).)
Databáze: MEDLINE
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