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Long-term survivors of early breast cancer treated with chemotherapy are characterized by a pro-inflammatory biomarker profile compared to matched controls.

与匹配的对照相比,早期乳腺癌化疗治疗的长期幸存者的特征在于促炎生物标志物谱。

  • 影响因子:7.31
  • DOI:10.1002/ejhf.1758
  • 作者列表:"Tromp J","Boerman LM","Sama IE","Maass SWMC","Maduro JH","Hummel YM","Berger MY","de Bock GH","Gietema JA","Berendsen AJ","van der Meer P
  • 发表时间:2020-02-20
Abstract

BACKGROUND:Chemo- and radiotherapy for breast cancer (BC) can lead to cardiotoxicity even years after the initial treatment. The pathophysiology behind these late cardiac effects is poorly understood. Therefore, we studied a large panel of biomarkers from different pathophysiological domains in long-term BC survivors, and compared these to matched controls. METHODS AND RESULTS:In total 91 biomarkers were measured in 688 subjects: 342 BC survivors stratified either to treatment with chemotherapy ± radiotherapy (n = 170) or radiotherapy alone (n = 172) and matched controls. Mean age was 59 ± 9 years and 65 ± 8 years for women treated with chemotherapy ± radiotherapy and radiotherapy alone, respectively, with a mean time since treatment of 11 ± 5.5 years. No biomarkers were differentially expressed in survivors treated with radiotherapy alone vs. controls (P for all >0.1). In sharp contrast, a total of 19 biomarkers were elevated, relative to controls, in BC survivors treated with chemotherapy ± radiotherapy after correction for multiple comparisons (P <0.05 for all). Network analysis revealed upregulation of pathways relating to collagen degradation and activation of matrix metalloproteinases. Furthermore, several inflammatory biomarkers including growth differentiation factor 15, monocyte chemoattractant protein 1, chemokine (C-X-C motif) ligand 16, tumour necrosis factor super family member 13b and proprotein convertase subtilisin/kexin type 9, elevated in survivors treated with chemotherapy, showed an independent association with lower left ventricular ejection fraction. CONCLUSION:Breast cancer survivors treated with chemotherapy ± radiotherapy show a distinct biomarker profile associated with mild cardiac dysfunction even 10 years after treatment. These results suggest that an ongoing pro-inflammatory state and activation of matrix metalloproteinases following initial treatment with chemotherapy might play a role in the observed cardiac dysfunction in late BC survivors.

摘要

背景: 乳腺癌的化疗和放疗 (BC) 可导致心脏毒性,甚至在初始治疗后数年。这些晚期心脏效应背后的病理生理学还知之甚少。因此,我们在长期 BC 幸存者中研究了一组来自不同病理生理结构域的大型生物标志物,并将其与匹配的对照进行了比较。 方法和结果: 在 688 名受试者中总共测量了 91 个生物标志物: 342 例 bc 幸存者,分为化疗 + 放疗 (n = 170) 或单纯放疗 (n = 172) 和匹配的控件。接受化疗 + 放疗和单纯放疗的女性平均年龄分别为 59 ± 9 岁和 65 ± 8 岁, 自治疗以来的平均时间为 11 ± 5.5 年。在接受单纯放疗治疗的幸存者与对照组中没有生物标志物的差异表达 (P 均&gt; 0.1)。与此形成鲜明对比的是,经过多重比较校正后,接受化疗 ± 放疗的 BC 幸存者中,相对于对照组,总共有 19 个生物标志物升高 (P

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发表时间:2020-04-01
DOI:10.1002/ijc.32847
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影响因子:4.88
发表时间:2020-03-01
DOI:10.1016/j.ecoenv.2019.110098
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影响因子:6.50
发表时间:2020-03-31
来源期刊:Cancer letters
DOI:10.1016/j.canlet.2019.12.039
作者列表:["Zhou Z","Zhou Q","Wu X","Xu S","Hu X","Tao X","Li B","Peng J","Li D","Shen L","Cao Y","Yang L"]

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