ABCB1、FCGR2A 和 FCGR3A 多态性与接受一线紫杉烷类联合曲妥珠单抗化疗治疗的 HER2 阳性转移性乳腺癌患者的关系。

ABCB1, FCGR2A, and FCGR3A polymorphisms in patients with HER2-positive metastatic breast cancer who were treated with first-line taxane plus trastuzumab chemotherapy.

机构信息

Department of Internal Medicine, Seoul National University College of Medicine, Korea.

出版信息

Oncology. 2012;83(4):218-27. doi: 10.1159/000341359. Epub 2012 Aug 16.

DOI:10.1159/000341359

PMID:22906996

Abstract

OBJECTIVE

The aim of this study was to elucidate clinical implications of ABCB1, FCGR2A, and FCGR3A polymorphisms in patients with HER2-positive metastatic breast cancer (MBC) after taxane plus trastuzumab (TH) chemotherapy.

METHODS

Using genomic DNA samples extracted from mononuclear cells of consecutive patients with HER2-positive MBC who received first-line TH, we analyzed five polymorphisms (ABCB1 1236C>T, ABCB1 2677G>T/A, ABCB1 3435C>T, FCGR2A 131H/R, and FCGR3A 158V/F) and then correlated them with the response rate, progression-free survival (PFS), overall survival (OS), and adverse events of patients.

RESULTS

A total of 57 women were analyzed. The median age was 46 years (range 27-72). ABCB1 2677T carriers had a longer PFS (p = 0.037) along with a tendency toward a longer OS (p = 0.057). ABCB1 3435CC genotype carriers had a shorter PFS (p = 0.039) along with a tendency toward a shorter OS (p = 0.093). In combined analysis, PFS was significantly longer in ABCB1 1236CC and/or 2677TT carriers compared to the others (p = 0.006). FCGR2A 131H/R and FCGR3A 158V/F polymorphisms were not significantly associated with response rate, PFS, and OS.

CONCLUSIONS

Our data support that ABCB1 polymorphisms may predict PFS after first-line TH chemotherapy in patients with HER2-positive MBC. In contrast, FCGR2A 131H/R and FCGR3A 158V/F polymorphisms could not predict treatment outcomes.

摘要

目的

本研究旨在阐明 ABCB1、FCGR2A 和 FCGR3A 多态性在接受紫杉烷联合曲妥珠单抗（TH）化疗的 HER2 阳性转移性乳腺癌（MBC）患者中的临床意义。

方法

使用从连续接受一线 TH 化疗的 HER2 阳性 MBC 患者单核细胞中提取的基因组 DNA 样本，我们分析了五个多态性（ABCB1 1236C>T、ABCB1 2677G>T/A、ABCB1 3435C>T、FCGR2A 131H/R 和 FCGR3A 158V/F），并将其与患者的缓解率、无进展生存期（PFS）、总生存期（OS）和不良事件相关联。

结果

共分析了 57 例女性患者。中位年龄为 46 岁（范围 27-72）。ABCB1 2677T 携带者的 PFS 较长（p=0.037），OS 也有延长趋势（p=0.057）。ABCB1 3435CC 基因型携带者的 PFS 较短（p=0.039），OS 也有缩短趋势（p=0.093）。在联合分析中，与其他患者相比，ABCB1 1236CC 和/或 2677TT 携带者的 PFS 显著更长（p=0.006）。FCGR2A 131H/R 和 FCGR3A 158V/F 多态性与缓解率、PFS 和 OS 无显著相关性。