乳腺癌中的表皮生长因子受体：与早期复发和死亡的关联、对激素的反应不佳以及与neu的相互作用

Epidermal growth factor receptors in breast cancer: association with early relapse and death, poor response to hormones and interactions with neu.

作者信息

Harris A L, Nicholson S, Sainsbury J R, Farndon J, Wright C

机构信息

Imperial Cancer Research Fund Clinical Oncology Unit, John Radcliffe Hospital, Headington, Oxford, U.K.

出版信息

J Steroid Biochem. 1989;34(1-6):123-31. doi: 10.1016/0022-4731(89)90072-1.

DOI:10.1016/0022-4731(89)90072-1

PMID:2576295

Abstract

Epidermal growth factor receptors (EGFRs) were measured in 221 primary breast cancers by ligand binding with 125I-labelled EGF, and high-affinity sites were quantitated. There was a highly significant inverse relationship between oestrogen receptor (ER) and EGFR (15 EGFR-positive [EGFR+]ER+ and 92 EGFR-negative [EGFR-]ER+: 54 EGFR- ER- and 60 EGFR+ ER-). The relapse-free survival and overall survival were significantly shorter for EGFR+ vs EGFR- tumours (P less than 0.001) by about 2 yr in the case of relapse-free survival. When ER- tumours were substratified by EGFR status, the EGFR- ER- tumours had a prognosis almost as good as the ER+ tumours. In 31 of 184 cases, high expression of neu, correlating with amplification, was found. Expression of neu conferred similar poor prognosis to EGFR expression in all prognostic subgroups. Coexpression of neu and EGFR had an additive adverse effect. Epidermal growth factor receptors (EGFR) and oestrogen receptors (ER) were analysed in 221 patients with primary operable breast cancer by means of radioligand assays. After median follow-up of 24 months (range 3-60 months), there had been recurrences in 99 patients, of whom 72 (median age 56 yr, range 32-77 yr) received tamoxifen alone as first-line treatment for recurrence. 14 patients (19%) showed a response to this therapy and 58 (81%) did not. Of 32 ER+ tumours, 12 (37.5%) showed an objective response to tamoxifen compared with only 2 of 40 (5%) ER- tumours (P less than 0.005). Of 35 EGFR+ tumours, 3 (8.5%) achieved an objective response compared with 11 of 36 (30%) EGFR tumours (P less than 0.05). Only 1 of 28 EGFR+, ER- tumours achieved an objective response. Including patients whose disease remained stable for more than 6 months with the responders, however, EGFR status was a better predictor of response to tamoxifen; 15 of 37 EGFR- patients and 5 of 35 EGFR+ patients responded (P less than 0.01).

摘要

通过与¹²⁵I标记的表皮生长因子（EGF）进行配体结合，对221例原发性乳腺癌中的表皮生长因子受体（EGFR）进行了检测，并对高亲和力位点进行了定量分析。雌激素受体（ER）与EGFR之间存在高度显著的负相关关系（15例EGFR阳性[EGFR+]ER+和92例EGFR阴性[EGFR-]ER+；54例EGFR- ER-和60例EGFR+ ER-）。EGFR+肿瘤的无复发生存期和总生存期明显短于EGFR-肿瘤（P<0.001），无复发生存期大约短2年。当ER-肿瘤按EGFR状态分层时，EGFR- ER-肿瘤的预后几乎与ER+肿瘤一样好。在184例病例中的31例中，发现了与扩增相关的neu高表达。在所有预后亚组中，neu表达与EGFR表达一样，预后较差。neu和EGFR的共表达具有累加的不良影响。通过放射性配体分析，对221例原发性可手术乳腺癌患者的表皮生长因子受体（EGFR）和雌激素受体（ER）进行了分析。中位随访24个月（范围3 - 60个月）后，99例患者出现复发，其中72例（中位年龄56岁，范围32 - 77岁）单独接受他莫昔芬作为复发的一线治疗。14例患者（19%）对该治疗有反应，58例（81%）无反应。在32例ER+肿瘤中，12例（37.5%）对他莫昔芬有客观反应，而在40例ER-肿瘤中只有2例（5%）有反应（P<0.005）。在35例EGFR+肿瘤中，3例（8.5%）达到客观反应，而在36例EGFR-肿瘤中有11例（30%）有反应（P<0.05）。28例EGFR+、ER-肿瘤中只有1例达到客观反应。然而，将疾病稳定超过6个月的患者包括在有反应者中，EGFR状态是他莫昔芬反应的更好预测指标；37例EGFR-患者中有15例有反应，35例EGFR+患者中有5例有反应（P<0.01）。