Suppr
超能文献

定量 HER2 蛋白水平可预测曲妥珠单抗治疗的转移性乳腺癌荧光原位杂交阳性患者的结局。

Quantitative HER2 protein levels predict outcome in fluorescence in situ hybridization-positive patients with metastatic breast cancer treated with trastuzumab.

机构信息

Division of Hematology-Oncology, Penn State/Hershey Medical Center, Hershey, PA, USA.

出版信息

Cancer. 2010 Nov 15;116(22):5168-78. doi: 10.1002/cncr.25430.

DOI:10.1002/cncr.25430

PMID:20661914

Abstract

BACKGROUND

Only a portion of breast cancer patients currently selected for trastuzumab therapy respond.

METHODS

Using a novel assay (HERmark) to quantify total human epidermal growth factor receptor 2 (HER2) expression, the authors examined outcomes in 102 trastuzumab-treated metastatic breast cancer patients previously assessed as immunohistochemistry (IHC) 3+ by local but not central IHC, or fluorescence in situ hybridization (FISH) positive, and then retested by central FISH.

RESULTS

Of 102 MBC patients previously scored as IHC 3+ or 2+/FISH-positive and treated with trastuzumab-containing regimens, 98 had both central FISH and HER2 total expression values. Sixty-six of 76 central FISH-positive patients (87%) had high HER2 total expression levels (concordant positive), and 19 of 22 central FISH-negative patients (86%) were HER2 total expression low (concordant negative). Fourteen percent (3 of 22) of central FISH-negative patients were HER2 total expression high (discordant HER2 total expression high), and 13% (10 of 76) of central FISH-positive patients were HER2 total expression low (discordant HER2 total expression low). The concordant positive group had a significantly longer time to progression (TTP, median = 11.3 months) compared with the concordant negative group (median TTP, 4.5 months; hazard ratio [HR] = 0.42, P < .001), and also compared with the discordant HER2 total expression low group (median TTP, 3.7 months; HR = 0.43, P = .01). The discordant HER2 total expression low group behaved similarly compared with concordant negatives (HR = 1, P = .99). In analyses restricted to central FISH-positive patients only (n = 77), Cox proportional hazards multivariate regression identified HER2 total expression as an independent predictor of TTP (HR = 0.29, P = .0015) and overall survival (HR = 0.19, P < .001).

CONCLUSIONS

A subset of patients with HER2 gene amplification by FISH express low levels of HER2 protein and have reduced response to trastuzumab-containing therapy, similar to FISH-negative patients. This cohort represents a training dataset, and the observed relationships and derived cutoffs require validation in an independent cohort of trastuzumab-treated metastatic breast cancer patients.

摘要

背景

目前接受曲妥珠单抗治疗的乳腺癌患者中只有一部分有反应。

方法

作者使用一种新的检测方法（HERmark）来定量检测总人表皮生长因子受体 2（HER2）的表达，对 102 例经曲妥珠单抗治疗的转移性乳腺癌患者进行了检测，这些患者之前通过局部免疫组化（IHC）检测为 3+，但未通过中心 IHC 或荧光原位杂交（FISH）检测为阳性，然后通过中心 FISH 进行了重新检测。

结果

在 102 例之前被评分 IHC 3+或 2+/FISH 阳性且接受曲妥珠单抗治疗的 MBC 患者中，98 例患者同时具有中心 FISH 和 HER2 总表达值。在 76 例中心 FISH 阳性患者中，66 例（87%）有高 HER2 总表达水平（一致性阳性），22 例中心 FISH 阴性患者中 19 例（86%） HER2 总表达水平较低（一致性阴性）。22 例中心 FISH 阴性患者中有 14%（3 例）的 HER2 总表达水平较高（不一致的 HER2 总表达水平较高），76 例中心 FISH 阳性患者中有 13%（10 例）的 HER2 总表达水平较低（不一致的 HER2 总表达水平较低）。一致性阳性组的无进展生存期（TTP，中位=11.3 个月）明显长于一致性阴性组（中位 TTP，4.5 个月；风险比[HR] = 0.42，P <.001），也长于不一致的 HER2 总表达水平较低组（中位 TTP，3.7 个月；HR = 0.43，P =.01）。不一致的 HER2 总表达水平较低组与一致性阴性组相似（HR = 1，P =.99）。在仅对中心 FISH 阳性患者（n = 77）进行的分析中，Cox 比例风险多变量回归分析确定 HER2 总表达是 TTP（HR = 0.29，P =.0015）和总生存（HR = 0.19，P <.001）的独立预测因子。