Polychronis Andreas, Sinnett H Dudley, Hadjiminas Dimitri, Singhal Hemant, Mansi Janine L, Shivapatham Dharsha, Shousha Sami, Jiang Jie, Peston David, Barrett Nigel, Vigushin David, Morrison Ken, Beresford Emma, Ali Simak, Slade Martin J, Coombes R Charles
Cancer Research UK Laboratories, Department of Cancer Medicine, Imperial College, London, UK.
Lancet Oncol. 2005 Jun;6(6):383-91. doi: 10.1016/S1470-2045(05)70176-5.
Some oestrogen-receptor (ER) positive breast cancers express epidermal growth factor receptor (EGFR), but whether inhibition of EGFR can suppress proliferation of breast cancer cells and ER function is not known.
In a double-blind, placebo-controlled randomised trial of 56 postmenopausal patients with ER-positive and EGFR-positive primary breast cancer, 27 women were randomly assigned to the tyrosine-kinase inhibitor of EGFR gefitinib (250 mg given orally once a day) and the aromatase inhibitor anastrozole (1 mg given orally once a day), and 29 women to gefitinib (250 mg given orally once a day) and placebo of identical appearance to anastrozole given orally once a day, all given for 4-6 weeks before surgery. Primary outcome was inhibition of tumour-cell proliferation, as measured by Ki67 antigen labelling index. Secondary outcomes were reduction in EGFR phosphorylation at Tyr 845, reduction in ER phosphorylation at Ser 118, tumour size, and toxic effects. Analyses were by intention to treat.
Patients assigned gefitinib and anastrozole had a greater reduction from pretreatment values in proliferation-related Ki67 labelling index than did those assigned gefitinib alone (mean % reduction 98.0 [95% CI 96.1-98.9] vs 92.4 [85.1-96.1]; difference between groups 5.6% [5.1-6.0], p=0.0054). Tumour size was reduced by 30-99% (partial response) in 14 of 28 patients assigned gefitinib and [corrected]in 12 of 22 assigned gefitinib, as assessed by ultrasonography. Reduction in phosphorylation of ER at Ser 118 was similar for both groups. Treatment was well tolerated and much the same for both groups.
Single-agent gefitinib and gefitinib combined with anastrozole are well-tolerated and effective treatments for reducing the size of breast tumours and levels of ER phosphorylation when given as neoadjuvant therapy.
一些雌激素受体（ER）阳性乳腺癌表达表皮生长因子受体（EGFR），但抑制EGFR是否能抑制乳腺癌细胞增殖及ER功能尚不清楚。
在一项针对56例绝经后ER阳性且EGFR阳性原发性乳腺癌患者的双盲、安慰剂对照随机试验中，27名女性被随机分配接受EGFR酪氨酸激酶抑制剂吉非替尼（每日口服250毫克）和芳香化酶抑制剂阿那曲唑（每日口服1毫克），29名女性被分配接受吉非替尼（每日口服250毫克）和外观与阿那曲唑相同的安慰剂，每日口服一次，所有治疗均在手术前进行4 - 6周。主要结局是通过Ki67抗原标记指数测量的肿瘤细胞增殖抑制情况。次要结局包括Tyr 845处EGFR磷酸化的降低、Ser 118处ER磷酸化的降低、肿瘤大小及毒性作用。分析采用意向性治疗。
与仅接受吉非替尼治疗的患者相比，接受吉非替尼和阿那曲唑治疗的患者增殖相关的Ki67标记指数较治疗前值降低幅度更大（平均降低百分比98.0 [95%可信区间96.1 - 98.9] 对92.4 [85.1 - 96.1]；组间差异5.6% [5.1 - 6.0]，p = 0.0054）。根据超声检查评估，在接受吉非替尼治疗的28例患者中有14例、接受吉非替尼和安慰剂治疗的22例患者中有12例肿瘤大小缩小30% - 99%（部分缓解）。两组Ser 118处ER磷酸化的降低情况相似。治疗耐受性良好，两组情况大致相同。
作为新辅助治疗，单药吉非替尼以及吉非替尼联合阿那曲唑在降低乳腺肿瘤大小和ER磷酸化水平方面耐受性良好且有效。
