Chevillard S, Pouillart P, Beldjord C, Asselain B, Beuzeboc P, Magdelénat H, Vielh P
Département de Transfert, Institut Curie, Paris, France.
Cancer. 1996 Jan 15;77(2):292-300. doi: 10.1002/(SICI)1097-0142(19960115)77:2<292::AID-CNCR11>3.0.CO;2-X.
The authors examined the relevance of S-phase fraction (SPF) and multidrug resistance (MDR) phenotype as predictive tests of breast cancer response in a series of patients treated by conventional doses of neoadjuvant chemotherapy with (FAC) or without (FTC) doxorubicin.
Fine needle samplings of tumors were used to measure SPF by flow cytometry before treatment (Day 0), and to assess the MDR phenotype using semiquantified reverse transcriptase polymerase chain reaction and immunocytochemistry, before and after (Days 8 and 28) the first cycle of chemotherapy.
Measurement of SPF before treatment was significantly associated with clinical response, but sequential assessment of MDR phenotype identified three groups of tumors with distinct outcomes: (1) tumors with a positive and constant expression of MDR1, in which prediction of resistance was restricted to patients treated by FAC; (2) tumors without any detectable expression, in which resistance to FAC or FTC treatments was rarely observed; and (3) tumors with an early (Day 8) acquired or increased MDR1 gene expression, which were always resistant to therapy to both treatment regimens. These results were confirmed at the protein level.
Sequential assessment of MDR phenotype is a relevant tool for monitoring breast cancer response in neoadjuvant chemotherapy.
作者在一系列接受常规剂量新辅助化疗（含阿霉素的FAC方案或不含阿霉素的FTC方案）治疗的患者中，研究了S期细胞比例（SPF）和多药耐药（MDR）表型作为乳腺癌反应预测指标的相关性。
在治疗前（第0天），通过细针穿刺肿瘤取样，采用流式细胞术测量SPF；在化疗第一周期前及化疗后（第8天和第28天），使用半定量逆转录聚合酶链反应和免疫细胞化学评估MDR表型。
治疗前SPF的测量结果与临床反应显著相关，但对MDR表型的连续评估确定了三组预后不同的肿瘤：（1）MDR1呈阳性且持续表达的肿瘤，对其耐药的预测仅限于接受FAC方案治疗的患者；（2）未检测到任何表达的肿瘤，很少观察到对FAC或FTC治疗耐药；（3）在第8天出现MDR1基因早期获得性表达或表达增加的肿瘤，对两种治疗方案均始终耐药。这些结果在蛋白质水平得到证实。
对MDR表型进行连续评估是监测新辅助化疗中乳腺癌反应的一种有效手段。
