Souder Christopher, Leitzel Kim, Ali Suhail M, Demers Laurence, Evans Dean B, Chaudri-Ross Hilary A, Hackl Wolfgang, Hamer Peter, Carney Walter, Lipton Allan
Department of Hematology/Oncology, Hershey Medical Center, Pennsylvania State University, Hershey, Pennsylvania 17033, USA.
Cancer. 2006 Nov 15;107(10):2337-45. doi: 10.1002/cncr.22255.
Epidermal growth factor receptor (EGFR, HER-1, and erbB1) is overexpressed in primary breast cancer and had been identified as a poor prognostic factor.
Pretreatment serum EGFR levels were quantified by using an enzyme-linked immunoadsorbent assay in a Phase III first-line trial of letrozole and tamoxifen and were correlated with patient outcomes.
Serum EGFR levels in a control group of 117 healthy, postmenopausal women measured 64.1 +/- 13.3 ng/mL (mean +/- standard deviation). Using a cutoff EGFR level of 44.1 ng/mL from the control group (5% nonparametric method), 53 of 535 patients (10%) had decreased serum levels of EGFR. Patients with decreased serum EGFR had no significant difference in objective response rate (ORR), clinical benefit rate (CBR), time to progression (TTP), or time to treatment failure (TTF); however, they did have significantly reduced survival compared with patients who had normal serum EGFR levels (median survival, 23.3 months vs. 30.9 months; P = .007). A combined analysis of pretreatment serum EGFR and HER-2 yielded no additional predictive information for ORR, CBR, TTP, or TTF compared to serum HER-2 alone. However, in the current analysis, a subgroup of patients who had decreased serum EGFR and normal serum HER-2 was identified (n = 39 of 535 patients; 7.3%) that had significantly reduced survival compared with patients who had normal serum levels of both EGFR and HER-2 (median survival, 23.5 months vs. 37.1 months; P = .005). In multivariate analysis, a decreased serum EGFR level remained a significant independent prognostic factor for decreased survival (hazards ratio, 1.58; P = .007).
In patients who had metastatic breast cancer, decreased serum EGFR/normal serum HER-2 predicted shorter survival compared with patients who had normal levels of serum EGFR/HER-2. This patient subgroup deserves further study to assess their response to and selection for anti-EGFR-directed therapies.
表皮生长因子受体（EGFR、HER-1和erbB1）在原发性乳腺癌中过表达，已被确定为不良预后因素。
在一项来曲唑和他莫昔芬的III期一线试验中，采用酶联免疫吸附测定法对预处理血清EGFR水平进行定量，并与患者预后相关联。
117名健康绝经后女性对照组的血清EGFR水平为64.1±13.3 ng/mL（平均值±标准差）。使用对照组中44.1 ng/mL的EGFR临界值水平（5%非参数法），535例患者中有53例（10%）血清EGFR水平降低。血清EGFR降低的患者在客观缓解率（ORR）、临床受益率（CBR）、进展时间（TTP）或治疗失败时间（TTF）方面无显著差异；然而，与血清EGFR水平正常的患者相比，他们的生存期显著缩短（中位生存期，23.3个月对30.9个月；P = 0.007）。与单独检测血清HER-2相比，预处理血清EGFR和HER-2的联合分析在ORR、CBR、TTP或TTF方面未产生额外的预测信息。然而，在当前分析中，确定了一个血清EGFR降低且血清HER-2正常的患者亚组（535例患者中有39例；7.3%），与血清EGFR和HER-2水平均正常的患者相比，其生存期显著缩短（中位生存期，23.5个月对37.1个月；P = 0.005）。在多变量分析中，血清EGFR水平降低仍然是生存期缩短的显著独立预后因素（风险比，1.58；P = 0.007）。
在转移性乳腺癌患者中，与血清EGFR/HER-2水平正常的患者相比，血清EGFR降低/血清HER-2正常预示生存期较短。该患者亚组值得进一步研究，以评估他们对EGFR靶向治疗的反应和选择。
