A case of metastatic breast cancer with outgrowth of HER2-negative cells after eradication of HER2-positive cells by humanized anti-HER2 monoclonal antibody (trastuzumab) combined with docetaxel
A case of metastatic breast cancer with outgrowth of HER2-negative cells after eradication of HER2-positive cells by humanized anti-HER2 monoclonal antibody (trastuzumab) combined with docetaxel
复制标题
DOI：
10.1016/j.humpath.2003.05.003
复制
发表时间：
2004-03-01
期刊：
影响因子：
3.3
通讯作者：
Ooi, A
中科院分区：
文献类型：
--
作者：
Kunitomo, K;Inoue, S;Ooi, A
一位38岁的左乳房癌症患者接受了改良的乳房根治术和淋巴结清扫术。21个月后，出现大量肝转移及胸膜癌。肝转移对曲妥珠单抗联合多西他赛化疗完全有效，但胸膜癌对治疗难治。荧光原位杂交显示，淋巴结原发肿瘤和转移瘤均由HER2扩增阳性和HER2扩增阴性的癌细胞组成。该分析还在化疗结束时采集的胸腔积液中检测到HER2扩增的单个细胞，但四次后续试验均未发现扩增细胞。推测在肝转移中，曲妥珠单抗对HER扩增和非扩增的癌细胞都有细胞毒性，可能是通过其抗血管生成作用起作用的。然而，在胸腔积液中，曲妥珠单抗对HER2扩增细胞的作用更为特异性，并导致缺乏HER2受体表达的癌细胞生长。
A 38-year-old woman with cancer of the left breast underwent a modified radical mastectomy with lymph node dissection. Twenty-one months later, massive liver metastases and pleural carcinomatosis occurred. The liver metastases responded completely to chemotherapy with trastuzumab combined with docetaxel, but the pleural carcinomatosis was refractory to the therapy. Fluorescence in situ hybridization showed that both the primary tumor and the metastatic tumors of the lymph nodes were composed of HER2 amplification-positive and HER2 amplification-negative cancer cells. This analysis also detected a single cell with HER2 amplification in the pleural effusion that was taken at the completion of the chemotherapy, but four follow-up tests showed no amplified cells. It is speculated that in the liver metastases, the trastuzumab was cytotoxic to both HER amplified and nonamplified cancer cells and may have acted through its antiangiogenic effect. However, in the pleural effusion, the effect of trastuzumab was more specific to HER2-amplified cells and caused outgrowth of cancer cells lacking expression of HER2 receptors.