Epidermal growth factor receptor expression in breast cancer association with biologic phenotype and clinical outcomes.
Epidermal growth factor receptor expression in breast cancer association with biologic phenotype and clinical outcomes.
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DOI：
10.1002/cncr.24816
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发表时间：
2010-03-01
期刊：
影响因子：
6.2
通讯作者：
Elledge, Richard M.
中科院分区：
文献类型：
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作者：
Rimawi, Mothaffar F.;Shetty, Priya B.;Weiss, Heidi L.;Schiff, Rachel;Osborne, C. Kent;Chamness, Gary C.;Elledge, Richard M.
在临床前乳腺癌模型中，EGFR的表达与侵袭性表型相关，但在临床研究中，EGFR与不良预后的关系并不一致。我们假设，当集中和统一评估时，EGFR在人类乳腺肿瘤中的表达与侵袭性表型和对系统治疗的抵抗有关。在一个47,286名乳腺癌患者的数据库中，已知2,567名患者的EGFR状态。表皮生长因子受体水平通过配体结合试验进行集中检测，≥为10fmoL/mg的肿瘤被认为是前瞻性的阳性。比较EGFR阳性和阴性肿瘤的临床和生物学特征。临床结果根据系统治疗状况进行评估。2567个肿瘤中有475个(18%)EGFR阳性。表皮生长因子受体阳性的肿瘤在年轻女性和黑人女性中更常见，更大，S期比例更高，更有可能是非整倍体。表皮生长因子受体阳性的肿瘤更有可能是hER2阳性(26%比16%，p<；0.0001)，但不太可能是ER阳性(60%比88%，p<；0.0001)或PR阳性(26%比65%，p<；0.0001)。在多因素分析中，EGFR的表达与DFS(HR=1.66，95%CI=1.4~2.41，p=0.007)和OS(HR=1.98，95%CI=1.36~2.88，p=0.0004)独立相关，而与初治患者无关。在年轻和黑人女性的乳腺肿瘤中，EGFR的表达更为常见。它与较低的激素受体水平、较高的增殖、基因组不稳定和HER2过度表达有关。在接受辅助治疗的患者中，它与较高的复发风险相关。阻断EGFR可能会改善选定患者的预后。
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 2,567. EGFR levels were measured centrally by ligand binding assay, and tumors with ≥10 fmol/mg were prospectively deemed positive. Clinical and biological features of EGFR positive and negative tumors were compared. Clinical outcomes were assessed by systemic therapy status. 475 out of 2,567 tumors (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<0.0001), but less likely to be ER-positive (60% vs. 88%, p<0.0001), or PR-positive (26% vs. 65%, p<0.0001). In multivariate analyses, EGFR expression independently correlated with worse DFS (HR=1.66, 95% CI=1.4–2.41, p=0.007) and OS (HR=1.98, 95% CI=1.36–2.88, p=0.0004) 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 over-expression. It is correlated with higher risk of relapse in patients receiving adjuvant treatment. Blocking EGFR may improve outcome in selected patients.
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影响因子：
158.5
作者：
Lynch, TJ;Bell, DW;Haber, DA
通讯作者：
Haber, DA
影响因子：
50.5
作者：
Ferrero, JM;Ramaioli, A;Milano, G
通讯作者：
Milano, G
影响因子：
45.3
作者：
CLARK, GM;OSBORNE, CK;MCGUIRE, WL
通讯作者：
MCGUIRE, WL
影响因子：
3.4
作者：
Huang, HJ;Neven, P;Christiaens, MR
通讯作者：
Christiaens, MR
DOI：
10.1093/jnci/95.2.142
发表时间：
2003-01-15
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Konecny, G;Pauletti, G;Slamon, DJ
通讯作者：
Slamon, DJ