Jurisova Silvia, Karaba Marián, Minarik Gabriel, Benca Juraj, Sedlackova Tatiana, Manasova Daniela, Kalavska Katarina, Pindak Daniel, Mardiak Jozef, Mego Michal
2nd Department of Oncology, Faculty of Medicine, Comenius University, Bratislava 83310, Slovakia.
National Cancer Institute, Bratislava 83310, Slovakia.
Cancer Drug Resist. 2020 Mar 19;3(1):98-109. doi: 10.20517/cdr.2019.79. eCollection 2020.
Different types of chronic medication may affect breast cancer prognosis. Circulating tumor cells (CTCs) play an important role in cancer metastasis formation. There is no evidence of how chronic medication affects CTCs and breast cancer prognosis. The aim of this study was to evaluate association between chronic medication and CTCs in patients with primary breast cancer. This study involved 414 patients with stage I-III primary breast cancer. Chronic drug history was collected from patients' medical records and included all drugs that were prescribed for patients over at least the last 6 months prior to CTCs evaluation. CTCs were detected using a quantitative real-time polymerase chain reaction (qRT-PCR)-based method at the time of breast surgery. There was no association between CTCs, including their different subpopulations and chronic medication. Chronic medication using angiotensin-converting-enzyme inhibitors (ACEi), metformin, and insulin were associated with inferior disease-free survival (HR = 0.49, 95%CI 0.26-0.94, = 0.007 for ACEi; HR = 0.27, 95%CI 0.08-0.91, < 0.001 for metformin; and HR = 0.12, 95%CI 0.01-2.91, < 0.001 for insulin) and this was most pronounced in patients with epithelial to mesenchymal transition (CTC_EMT) phenotype. In multivariate analysis, chronic administration of metformin and/or insulin was an independent predictor of inferior outcome. Our findings show that there was no association between chronically used medication and CTCs in primary breast cancer patients. However, administration of ACEi, metformin, and/or insulin could negatively affect prognosis of patients with CTC_EMT.
不同类型的慢性药物治疗可能会影响乳腺癌的预后。循环肿瘤细胞（CTC）在癌症转移形成中起着重要作用。目前尚无证据表明慢性药物治疗如何影响CTC及乳腺癌预后。本研究旨在评估原发性乳腺癌患者中慢性药物治疗与CTC之间的关联。本研究纳入了414例I - III期原发性乳腺癌患者。从患者病历中收集慢性用药史，包括在CTC评估前至少过去6个月内给患者开的所有药物。在乳腺癌手术时，使用基于定量实时聚合酶链反应（qRT-PCR）的方法检测CTC。包括不同亚群的CTC与慢性药物治疗之间无关联。使用血管紧张素转换酶抑制剂（ACEi）、二甲双胍和胰岛素进行慢性药物治疗与无病生存期较差相关（ACEi的HR = 0.49，95%CI为0.26 - 0.94，P = 0.007；二甲双胍的HR = 0.27，95%CI为0.08 - 0.91，P < 0.001；胰岛素的HR = 0.12，95%CI为0.01 - 2.91，P < 0.001），且在具有上皮-间质转化（CTC_EMT）表型的患者中最为明显。在多变量分析中，长期使用二甲双胍和/或胰岛素是预后较差的独立预测因素。我们的研究结果表明，原发性乳腺癌患者长期使用的药物与CTC之间无关联。然而，使用ACEi、二甲双胍和/或胰岛素可能会对具有CTC_EMT的患者的预后产生负面影响。
