Sandström Josefine, Bomanson Jens, Pérez-Tenorio Gizeh, Jönsson Carolin, Nordenskjöld Bo, Fornander Tommy, Lindström Linda S, Stål Olle
Department of Biomedical and Clinical Sciences and Department of Oncology, 581 83 Linköping University, Linköping, Sweden.
Department of Oncology and Pathology, Karolinska Institute and University Hospital, Stockholm, Sweden.
NPJ Breast Cancer. 2024 Sep 6;10(1):78. doi: 10.1038/s41523-024-00688-6.
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.
GATA结合蛋白3（GATA3）对乳腺的正常发育至关重要，且与雌激素受体阳性（ER阳性）乳腺癌相关。在实验研究中，GATA3的缺失与上皮-间质转化（EMT）有关。我们在一组绝经后淋巴结阴性乳腺癌患者中研究肿瘤GATA3情况，这些患者被随机分配接受辅助他莫昔芬治疗或作为对照。通过免疫组织化学评估核GATA3表达，并用安捷伦微阵列评估GATA3基因表达。GATA3高核表达与ER阳性乳腺癌远处复发率较低相关（风险比[HR]=0.60，95%置信区间[CI]为0.39 - 0.93）。GATA3基因低表达与辅助他莫昔芬的长期获益有限相关（交互作用：p = 0.033）。GATA3基因表达与上皮标志物E-钙黏蛋白（CDH1）和叉头框蛋白A1（FOXA1）相关，而与几种间质标志物呈负相关。CDH1低表达与他莫昔芬获益微小相关（HR = 0.80（0.43 - 1.49）），而表达较高的患者显示出显著获益（HR = 0.33（0.20 - 0.55），交互作用：p = 0.029）。在ER阳性乳腺癌中，GATA3表达降低与EMT标志物以及他莫昔芬的长期获益不佳相关。
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