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首页> 外文期刊>Journal of Clinical Oncology >Breast cancer-specific mRNA transcripts presence in peripheral blood after adjuvant chemotherapy predicts poor survival among high-risk breast cancer patients treated with high-dose chemotherapy with peripheral blood stem cell support.
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Breast cancer-specific mRNA transcripts presence in peripheral blood after adjuvant chemotherapy predicts poor survival among high-risk breast cancer patients treated with high-dose chemotherapy with peripheral blood stem cell support.

机译：辅助化疗后外周血中存在乳腺癌特异性mRNA转录本，这预示着接受高剂量化疗和外周血干细胞支持治疗的高危乳腺癌患者的生存率较差。

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PURPOSE: To study the prognostic significance of the presence of breast cancer-specific mRNA transcripts in peripheral blood (PB), defined by serial analysis of gene expression, in high-risk breast cancer (HRBC) patients undergoing high-dose chemotherapy after receiving adjuvant chemotherapy. METHODS: From 1994 to 2000, 84 HRBC patients (median age, 44 years; > 10 nodes; 74%) received adjuvant chemotherapy (fluorouracil, epirubicin, and cyclophosphamide for six cycles [83%] or doxorubicin and cyclophosphamide followed by paclitaxel) before undergoing one course of cyclophosphamide plus thiotepa plus carboplatin (STAMP V). Radiotherapy or hormone therapy was administered whenever indicated. Aliquots of apheresis-mononuclear blood cells were frozen from each patient. mRNA was isolated using an automatic nucleic acid extractor based on the magnetic beads technology; reverse transcription was performed using random hexamers. Cytokeratin 19, HER-2, P1B, PS2, and EGP2 transcripts were quantified to B-glucuronidase by real-time polymerase chain reaction (RT-PCR) using a linear DNA probe marked with a quencher and reporter fluorophores used in RT-PCR. Presence of PB micrometastases, estrogen receptor and progesterone receptor status, tumor size, age, tumor grade, number of nodes affected, and treatment with paclitaxel were included in the statistical analysis. RESULTS: Median follow-up was 68.3 months (range, 6 months to 103 months). Forty-seven relapses (56%) and 35 deaths (41.7%) were registered. Both tumor size and presence of micrometastases reached statistical significance according to the Cox multivariate model. Relapse hazard ratio (HR) for those patients with PB micrometastases was 269% (P = .006); death HR, 300% (P = .011). Time relapse was 53 months longer for patients without micrometastases: 31.3 v 84.2 months (P = .021). CONCLUSION: PB micrometastases presence after adjuvant chemotherapy predicts both relapse and death more powerful than classical factors in HRBC patients undergoing high-dosechemotherapy. Micrometastases search using a gene panel appears to be a more accurate procedure than classical approaches involving only one or two genes.
机译：目的：研究通过基因表达系列分析确定的外周血（PB）中乳腺癌特异性mRNA转录物在接受佐剂后接受大剂量化疗的高危乳腺癌（HRBC）患者中的预后意义化学疗法。方法：从1994年到2000年，在84例HRBC患者（中位年龄为44岁;> 10个结点; 74％）接受辅助化疗（氟尿嘧啶，表柔比星和环磷酰胺为六个周期[83％]或阿霉素和环磷酰胺再为紫杉醇）之前接受一疗程的环磷酰胺加噻替帕加卡铂（STAMP V）。只要有指示，就进行放射疗法或激素疗法。从每位患者冷冻单采血液分离术-单核血细胞。使用基于磁珠技术的自动核酸提取器分离mRNA。使用随机六聚体进行逆转录。使用标记有淬灭剂的线性DNA探针和RT-PCR中使用的报告荧光团通过实时聚合酶链反应（RT-PCR）将细胞角蛋白19，HER-2，P1B，PS2和EGP2转录物定量为B-葡糖醛酸糖苷酶。统计分析包括PB微转移的存在，雌激素受体和孕激素受体的状态，肿瘤大小，年龄，肿瘤等级，受影响的淋巴结数目和紫杉醇治疗。结果：中位随访时间为68.3个月（范围6个月至103个月）。记录有47例复发（56％）和35例死亡（41.7％）。根据Cox多变量模型，肿瘤大小和微转移的存在均达到统计学意义。 PB微转移患者的复发风险比（HR）为269％（P = .006）;死亡HR，300％（P = .011）。没有微转移的患者，复发时间延长了53个月：31.3 v 84.2个月（P = .021）。结论：辅助化疗后PB微转移的存在预示着接受大剂量化疗的HRBC患者的复发和死亡均比经典因素更有效。与仅涉及一个或两个基因的经典方法相比，使用基因面板进行微转移搜索似乎是一种更准确的方法。

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