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糖皮质激素受体表达预示三阴性乳腺癌患者在接受不含紫杉烷、以蒽环类药物为基础的治疗时预后良好。

Glucocorticoid Receptor Expression Predicts Good Outcome in response to Taxane-Free, Anthracycline-Based Therapy in Triple Negative Breast Cancer.

作者信息

Elkashif Ahmed, Bingham Victoria, Haddock Paula, Humphries Matthew P, McQuaid Stephen, Mullan Paul B, McCarthy Helen O, Buckley Niamh E

机构信息

School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, UK.

Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast BT9 7AE, UK.

出版信息

J Oncol. 2020 May 20;2020:3712825. doi: 10.1155/2020/3712825. eCollection 2020.

Abstract

Triple negative breast cancer (TNBC) is a poor outcome subset of breast cancers characterised by the lack of expression of ER , PR, and HER2 amplification. It is a heterogeneous group of cancers which fail to derive benefit from modern, more targeted treatments such as Tamoxifen and Herceptin. Current standard of care (SoC) is cytotoxic chemotherapy, which is effective for some patients, with other patients deriving little/no benefit and lacking alternative treatments. This study has identified the glucocorticoid receptor (GR) as a potential predictive biomarker of response to anthracycline-based chemotherapy in triple negative breast cancer (TNBC). GR gene expression levels in patient samples were analysed through publicly available microarray datasets as well as protein expression through immunohistochemistry (IHC) and correlated with clinical/pathological outcomes, including survival. While the results confirmed previous observations that high GR expression is associated with poor outcome in response to taxane-based chemotherapy, this study shows for the first time that high GR expression is associated with improved outcomes in the context of anthracycline-based chemotherapy. GR therefore has the potential to be used as a predictive biomarker to guide treatment choices and ensure that patients derive the greatest benefit from first line treatment, avoiding unnecessary costs, side effects, and disease progression.

摘要

三阴性乳腺癌(TNBC)是乳腺癌中预后较差的一个亚组,其特征是雌激素受体(ER)、孕激素受体(PR)缺乏表达以及人表皮生长因子受体2(HER2)无扩增。它是一组异质性癌症,无法从他莫昔芬和赫赛汀等现代、更具针对性的治疗中获益。当前的标准治疗方案(SoC)是细胞毒性化疗,这种疗法对一些患者有效,但其他患者获益甚微或无获益,且缺乏替代治疗方法。本研究已确定糖皮质激素受体(GR)是三阴性乳腺癌(TNBC)中对蒽环类化疗反应的潜在预测生物标志物。通过公开可用的微阵列数据集分析患者样本中的GR基因表达水平,并通过免疫组织化学(IHC)分析蛋白质表达,并将其与包括生存在内的临床/病理结果相关联。虽然结果证实了先前的观察结果,即高GR表达与紫杉烷类化疗反应的不良预后相关,但本研究首次表明,在蒽环类化疗的背景下,高GR表达与改善的预后相关。因此,GR有潜力用作预测生物标志物,以指导治疗选择,并确保患者从一线治疗中获得最大益处,避免不必要的费用、副作用和疾病进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3318/7256765/42241a911dbd/JO2020-3712825.001.jpg

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