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Evaluation of the prognostic and predictive value of HER family mRNA expression in high-risk early breast cancer: A Hellenic Cooperative Oncology Group (HeCOG) study

机译:HER家族mRNA表达在高危早期乳腺癌中的预后和预测价值的评估:希腊合作肿瘤小组(HeCOG)研究

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The aim of the study was to evaluate the prognostic ability of the transcriptional profiling of the HER family genes in early breast cancer, as well as to investigate the predictive value of HER2 mRNA expression for adjuvant treatment with paclitaxel. RNA was extracted from 268 formalin-fixed paraffin-embedded (FFPE) tumour tissue samples of high-risk breast cancer patients enrolled in the randomised HE10/97 trial, evaluating the effect of dose-dense anthracycline-based sequential adjuvant chemotherapy with or without paclitaxel. The mRNA expression of all four HER family members was assessed by kinetic reverse transcription-polymerase chain reaction (kRT–PCR). The overall concordance between kRT–PCR and IHC/FISH for HER2 status determination was 74%. At a median follow-up of 8 years, multivariate analysis showed that EGFR and HER2 mRNA expression was associated with reduced overall survival (OS). HER3 and HER4 mRNA level had a favourable prognostic value in terms of OS and disease-free survival (DFS), respectively. Adjusting for HER2 mRNA expression, OS and DFS did not differ between treatment groups. These data indicate that EGFR as well as HER2 are prognostic factors of worse clinical outcomes, whereas HER3 and HER4 gene transcription is associated with better prognosis in high-risk early breast cancer. However, HER2 mRNA expression did not predict clinical benefit from paclitaxel. Kinetic RT–PCR represents an alternative method for evaluating the expression of HER family members in FFPE breast carcinomas.
机译:这项研究的目的是评估HER家族基因的转录谱在早期乳腺癌中的预后能力,以及研究HER2 mRNA表达对紫杉醇辅助治疗的预测价值。从参与HE10 / 97随机试验的高危乳腺癌患者的268种福尔马林固定石蜡包埋(FFPE)肿瘤组织样本中提取RNA,评估基于剂量密集型蒽环类药物的序贯辅助化疗联合或不联合紫杉醇的效果。通过动力学逆转录-聚合酶链反应(kRT-PCR)评估了所有四个HER家族成员的mRNA表达。 kRT-PCR和IHC / FISH在HER2状态测定中的总体一致性为74%。在8年的中位随访中,多变量分析表明EGFR和HER2 mRNA表达与总生存期(OS)降低有关。 HER3和HER4 mRNA水平分别在OS和无病生存期(DFS)方面具有良好的预后价值。调整HER2 mRNA表达,OS和DFS在治疗组之间没有差异。这些数据表明,EGFR和HER2是预后较差的预后因素,而HER3和HER4基因的转录与高危早期乳腺癌的预后较好有关。但是,HER2 mRNA表达不能预测紫杉醇的临床获益。动力学RT-PCR代表了另一种评估FFPE乳腺癌中HER家族成员表达的方法。

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