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P-糖蛋白:局部晚期乳腺癌诱导化疗药物反应的中间终点

P-glycoprotein: the intermediate end point of drug response to induction chemotherapy in locally advanced breast cancer.

作者信息

Chung H C, Rha S Y, Kim J H, Roh J K, Min J S, Lee K S, Kim B S, Lee K B

机构信息

Yonsei Cancer Center, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

出版信息

Breast Cancer Res Treat. 1997 Jan;42(1):65-72. doi: 10.1023/a:1005739525196.

DOI:10.1023/a:1005739525196
PMID:9116319
Abstract

Expression and clinical relevance of p-glycoprotein (p-gp) were evaluated in 31 cases of locally advanced breast cancer and 9 cases involving inflammatory breast cancer after induction chemotherapy. The de novo p-gp expression rate was 26% and increased up to 58% (p = 0.03) with the FAC (5-fluorouracil, adriamycin, cyclophosphamide) regimen. Although more clinically complete responders were found in the secondary p-gp negative group (p = 0.02), this difference was not found in pathological tumor response. Moreover, as the grade of the secondary p-gp expression increased, the chemotherapeutic effect decreased, suggesting an inverse relationship between p-gp expression and drug effect (p = 0.04). When we subgrouped the patients into 4 groups using these two parameters, p-gp negative patients presenting with a high drug effect showed a low recurrence rate (p = 0.05) and marginal survival benefits (p = 0.09) as opposed to patients with a low drug effect. But in p-gp positive groups, the recurrence rate was the same between the two groups regardless of the drug effect. Thus, in the p-gp negative patient with a high drug effect, adjuvant chemotherapy with the same regimen as induction chemotherapy may induce more prognostically favorable results. Therefore, clinical application of the secondary p-gp detection can be used as an intermediate endpoint in evaluating drug response for an induction regimen.

摘要

对31例局部晚期乳腺癌患者和9例诱导化疗后的炎性乳腺癌患者进行了P-糖蛋白(P-gp)表达及临床相关性评估。P-gp初始表达率为26%,采用FAC(5-氟尿嘧啶、阿霉素、环磷酰胺)方案后升至58%(P = 0.03)。虽然继发性P-gp阴性组中临床完全缓解者更多(P = 0.02),但在病理肿瘤反应方面未发现此差异。此外,随着继发性P-gp表达程度增加,化疗效果降低,提示P-gp表达与药物效果呈负相关(P = 0.04)。当我们使用这两个参数将患者分为4组时,与药物效果低的患者相比,药物效果高的P-gp阴性患者复发率低(P = 0.05)且生存获益微乎其微(P = 0.09)。但在P-gp阳性组中,无论药物效果如何,两组复发率相同。因此,对于药物效果高的P-gp阴性患者,采用与诱导化疗相同方案的辅助化疗可能会带来更有利于预后的结果。所以,继发性P-gp检测的临床应用可作为评估诱导方案药物反应的一个中间终点。

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