曲妥珠单抗辅助治疗 HER2 阳性乳腺癌的疗效及其影响因素

HER2 gene copy number status may influence clinical efficacy to anti-EGFR monoclonal antibodies in metastatic colorectal cancer patients.

机构信息

Institute of Pathology, Locarno 6600, Switzerland.

出版信息

Br J Cancer. 2013 Feb 19;108(3):668-75. doi: 10.1038/bjc.2013.4. Epub 2013 Jan 24.

DOI:10.1038/bjc.2013.4

PMID:23348520

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3593567/

Abstract

BACKGROUND

In metastatic colorectal cancer (mCRC), KRAS is the only validated biomarker used to select patients for administration of epidermal growth factor receptor (EGFR)-targeted therapies. To identify additional predictive markers, we investigated the importance of HER2, the primary EGFR dimerisation partner, in this particular disease.

METHODS

We evaluated the HER2 gene status by fluorescence in situ hybridisation (FISH) in 170 KRAS wild-type mCRC patients treated with cetuximab or panitumumab.

RESULTS

Depending on HER2 gene copy number status, patients showed three distinct cytogenetic profiles: 4% of patients had HER2 gene amplification (R:HER2/CEP17 ≥ 2) in all neoplastic cells (HER2-all-A), 61% of patients had HER2 gain due to polysomy or to gene amplification in minor clones (HER2-FISH+), and 35% of patients had no or slight HER2 gain (HER2-FISH-). These subgroups were significantly correlated with different clinical behaviours, in terms of response rate (RR; P=0.0006), progression-free survival (PFS; P<0.0001) and overall survival (OS; P<0.0001). Patients with HER2-all-A profile experienced the worst outcome, patients with HER2-FISH- profile showed an intermediate behaviour and patients with HER2-FISH+ profile were related to the highest survival probability (median PFS in months: 2.5 vs 3.9 vs 7.6, respectively; median OS in months: 4.2 vs 9.7 vs 13, respectively).

CONCLUSION

HER2 gene copy number status may influence the clinical response to anti-EGFR-targeted therapy in mCRC patients.

摘要

背景

在转移性结直肠癌（mCRC）中，KRAS 是唯一经验证的生物标志物，用于选择接受表皮生长因子受体（EGFR）靶向治疗的患者。为了确定其他预测标志物，我们研究了 HER2（EGFR 的主要二聚化伙伴）在这种特殊疾病中的重要性。

方法

我们通过荧光原位杂交（FISH）评估了 170 例 KRAS 野生型 mCRC 患者接受西妥昔单抗或帕尼单抗治疗的 HER2 基因状态。

结果

根据 HER2 基因拷贝数状态，患者表现出三种不同的细胞遗传学特征：4%的患者所有肿瘤细胞均存在 HER2 基因扩增（R：HER2/CEP17≥2）（HER2-all-A），61%的患者由于多倍体或次要克隆的基因扩增而存在 HER2 获得（HER2-FISH+*），35%的患者不存在或仅有轻微的 HER2 获得（HER2-FISH-）。这些亚组与不同的临床行为显著相关，包括缓解率（RR；P=0.0006）、无进展生存期（PFS；P<0.0001）和总生存期（OS；P<0.0001）。HER2-all-A 患者预后最差，HER2-FISH-患者表现出中等行为，HER2-FISH+*患者与最高的生存概率相关（中位 PFS 分别为 2.5、3.9 和 7.6 个月；中位 OS 分别为 4.2、9.7 和 13 个月）。