Mehta R R, McDermott J H, Hieken T J, Marler K C, Patel M K, Wild L D, Das Gupta T K
Department of Surgical Oncology and the Biostatistics Facility, University of Illinois at Chicago, 60612, USA.
J Clin Oncol. 1998 Jul;16(7):2409-16. doi: 10.1200/JCO.1998.16.7.2409.
To determine the significance of plasma c-erbB-2 levels to assess the extent of disease spread and to predict the response to chemotherapy in node-positive breast cancer patients.
We determined plasma levels of c-erbB-2 in 79 stages II and III breast cancer patients who received cyclophosphamide, methotrexate, and flourouracil (CMF)/cyclophosphamide, methotrexate, fluorouracil, vincristine, and prednisone (CMFVP) chemotherapy. All patients had a minimum follow-up of greater than 60 months or until disease recurrence. Plasma samples were obtained before and after chemotherapy. Plasma c-erbB-2 levels were quantified by enzyme-linked immunoassay. c-erbB-2 levels were analyzed in relation to the patients' axillary lymph node status, menopausal status, disease status, disease-free survival (DFS), and steroid receptor status of tumor.
Plasma c-erbB-2 levels varied widely in breast cancer patients. In general, when all patients were included in the analyses, plasma c-erbB-2 levels before chemotherapy correlated significantly with the number of positive axillary lymph nodes and with postchemotherapy c-erbB-2 levels. No association was observed between pre- or postchemotherapy c-erbB-2 levels and other variables (patients' age at diagnosis, receptor status of the tumor, or disease status). The prognostic significance of different factors (ie, nodal status [one to three v > three positive nodes], menopausal status [pre- v postmenopausal women], estrogen receptor [ER] status [ER+ v ER-], and pre- and postchemotherapy c-erbB-2 levels) in predicting DFS was determined in all study patients. Among the variables examined, nodal status was the strongest predictor of DFS in these patients. The second most significant prognostic marker was postchemotherapy c-erbB-2 level. Prechemotherapy c-erbB-2 levels showed prognostic significance for DFS in a subset of breast cancer patients (ie, patients with > three positive nodes). Patients with greater than three positive lymph nodes and those with greater than 100 fmol/mL of plasma c-erbB-2 levels before therapy had significantly shorter DFS than did those patients with 100 fmol/mL or less c-erbB-2 levels.
In breast cancer patients, determination of c-erbB-2 levels before therapy is an important biomarker to assess the extent of disease spread in the lymph nodes. Postchemotherapy c-erbB-2 levels are also a prognostic indicator for DFS in patients who receive chemotherapy. Finally, in a subgroup of patients with greater than three positive nodes, prechemotherapy c-erbB-2 levels are a prognostic marker for response of patients to standard chemotherapy.
确定血浆c-erbB-2水平对评估疾病扩散程度以及预测淋巴结阳性乳腺癌患者化疗反应的意义。
我们测定了79例接受环磷酰胺、甲氨蝶呤和氟尿嘧啶（CMF）/环磷酰胺、甲氨蝶呤、氟尿嘧啶、长春新碱和泼尼松（CMFVP）化疗的II期和III期乳腺癌患者的血浆c-erbB-2水平。所有患者的最短随访时间均超过60个月或直至疾病复发。在化疗前后采集血浆样本。通过酶联免疫吸附测定法定量血浆c-erbB-2水平。分析c-erbB-2水平与患者腋窝淋巴结状态、绝经状态、疾病状态、无病生存期（DFS）以及肿瘤的类固醇受体状态之间的关系。
乳腺癌患者的血浆c-erbB-2水平差异很大。总体而言，当将所有患者纳入分析时，化疗前血浆c-erbB-2水平与腋窝阳性淋巴结数量以及化疗后c-erbB-2水平显著相关。未观察到化疗前或化疗后c-erbB-2水平与其他变量（患者诊断时的年龄、肿瘤受体状态或疾病状态）之间存在关联。在所有研究患者中确定了不同因素（即淋巴结状态[1至3个与>3个阳性淋巴结]、绝经状态[绝经前与绝经后女性]、雌激素受体[ER]状态[ER+与ER-]以及化疗前和化疗后c-erbB-2水平）在预测DFS方面的预后意义。在检查的变量中，淋巴结状态是这些患者DFS的最强预测指标。第二显著的预后标志物是化疗后c-erbB-2水平。化疗前c-erbB-2水平在一部分乳腺癌患者（即阳性淋巴结>3个的患者）中显示出对DFS的预后意义。治疗前阳性淋巴结大于3个且血浆c-erbB-2水平大于100 fmol/mL的患者的DFS明显短于c-erbB-2水平为100 fmol/mL或更低的患者。
在乳腺癌患者中，治疗前测定c-erbB-2水平是评估淋巴结疾病扩散程度的重要生物标志物。化疗后c-erbB-2水平也是接受化疗患者DFS的预后指标。最后，在阳性淋巴结大于3个的患者亚组中，化疗前c-erbB-2水平是患者对标准化疗反应的预后标志物。
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