Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
Cancer. 2010 Mar 1;116(5):1234-42. doi: 10.1002/cncr.24816.
Epidermal growth factor receptor (EGFR) expression is associated with aggressive phenotypes in preclinical breast cancer models, but in clinical studies, EGFR has been inconsistently linked to poor outcome. We hypothesized that EGFR expression in human breast tumors, when centrally and uniformly assessed, is associated with an aggressive phenotype and resistance to systemic therapy.
In a database of 47,286 patients with breast cancer, EGFR status was known on 2567 tumors. EGFR levels were measured centrally by ligand binding assay, and tumors with > or =10 fmol/mg were prospectively deemed positive. Clinical and biological features of EGFR-positive and EGFR-negative tumors were compared. Clinical outcomes were assessed by systemic therapy status.
Of 2567 tumors, 475 (18%) were EGFR positive. EGFR-positive tumors were more common in younger and in black women, were larger, had a higher S-phase fraction, and were more likely to be aneuploid. EGFR-positive tumors were more likely to be HER2-positive (26% vs 16%, P < .0001), but less likely to be estrogen receptor-positive (60% vs 88%, P < .0001) or progesterone receptor-positive (26% vs 65%, P < .0001). In multivariate analyses, EGFR expression independently correlated with worse disease-free survival (hazard ratio [HR] = 1.66; 95% confidence interval [CI], 1.4-2.41, P = .007) and overall survival (HR = 1.98, 95% CI, 1.36-2.88, P = .0004) in treated patients, but not in untreated patients.
EGFR expression is more common in breast tumors in younger and black women. It is associated with lower hormone receptor levels, higher proliferation, genomic instability, and HER2 overexpression. It is correlated with higher risk of relapse in patients receiving adjuvant treatment. Blocking EGFR may improve outcome in selected patients.
表皮生长因子受体（EGFR）的表达与临床前乳腺癌模型中的侵袭性表型有关，但在临床研究中，EGFR 与不良预后的相关性并不一致。我们假设，在对 47286 例乳腺癌患者的数据库中，当对人类乳腺肿瘤进行集中且统一的评估时，EGFR 的表达与侵袭性表型和对全身治疗的耐药性有关。
在一个包含 47286 例乳腺癌患者的数据库中，有 2567 例肿瘤的 EGFR 状态已知。通过配体结合测定法对 EGFR 水平进行中心测量，并且将 > 或 = 10 fmol/mg 的肿瘤前瞻性地判定为阳性。比较 EGFR 阳性和 EGFR 阴性肿瘤的临床和生物学特征。通过全身治疗状态评估临床结局。
在 2567 例肿瘤中，有 475 例（18%）为 EGFR 阳性。EGFR 阳性肿瘤在年轻和黑人女性中更为常见，肿瘤更大，S 期分数更高，并且更可能是非整倍体。EGFR 阳性肿瘤更可能是 HER2 阳性（26%比 16%，P <.0001），而雌激素受体阳性（60%比 88%，P <.0001）或孕激素受体阳性（26%比 65%，P <.0001）的可能性较小。在多变量分析中，EGFR 表达独立地与无病生存期（风险比[HR] = 1.66；95%置信区间[CI]，1.4-2.41，P =.007）和总生存期（HR = 1.98，95% CI，1.36-2.88，P =.0004）相关，在接受治疗的患者中，但在未接受治疗的患者中则没有相关性。
EGFR 的表达在年轻和黑人女性的乳腺肿瘤中更为常见。它与较低的激素受体水平、较高的增殖、基因组不稳定性和 HER2 过表达有关。它与接受辅助治疗的患者复发风险增加相关。阻断 EGFR 可能会改善某些患者的预后。
