Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, Fulham Rd, London, SW3 6JB, UK.
Breast Cancer Res Treat. 2010 Oct;123(3):829-36. doi: 10.1007/s10549-010-1100-z. Epub 2010 Aug 10.
Cyclo-oxygenase 2 (COX-2) is implicated in the regulation of aromatase transcription in malignant breast tissue and has been considered as a potential target for tissue specific aromatase suppression. We initiated a randomised controlled pre-surgical study of celecoxib versus no treatment in women with primary breast cancer to determine the effects of COX-2 inhibition on markers of biological response. Postmenopausal women (50-80 years of age) with stage I or II, primary breast cancer, were randomised 2:1 to receive 400 mg/day celecoxib or no treatment for 14 days prior to surgery. A core biopsy was obtained pre- and post-treatment. Paired baseline and endpoint biopsies were analysed for Ki67, apoptosis, COX-2, CD31, estrogen receptor (ER) and progesterone receptor (PgR). Comparisons between the treatment groups were conducted using the Mann-Whitney test with a two-sided 5% significance. Of the 25 patients treated, 23 had evaluable data and 19 (83%) were ER positive. Overall the geometric mean change in Ki67, the primary end point, relative to baseline in the celecoxib arm was -16.6% (P = 0.056). The change in the no-treatment group was -8.1% (P = 0.24). There was no statistically significant difference in the change between the two groups. Celecoxib did not significantly affect apoptosis, COX-2, ER or PgR expression. There is only modest evidence for a biological effect of celecoxib in primary breast cancer. However, the trend towards a reduction in Ki67 in ER-positive breast cancer warrants further investigations in a larger cohort of patients.
环氧化酶 2（COX-2）参与调节恶性乳腺组织中的芳香酶转录，被认为是组织特异性芳香酶抑制的潜在靶点。我们启动了一项针对原发性乳腺癌患者的塞来昔布与无治疗对照的随机对照术前研究，以确定 COX-2 抑制对生物学反应标志物的影响。绝经后（50-80 岁）I 期或 II 期原发性乳腺癌患者按 2:1 随机分为接受塞来昔布 400mg/天或术前 14 天无治疗。在治疗前后获得核心活检。对配对的基线和终点活检进行 Ki67、凋亡、COX-2、CD31、雌激素受体（ER）和孕激素受体（PgR）分析。使用 Mann-Whitney 检验对治疗组进行双侧 5%显著性比较。在接受治疗的 25 例患者中，有 23 例有可评估数据，19 例（83%）为 ER 阳性。总体而言，塞来昔布组相对于基线的 Ki67（主要终点）的几何均数变化为-16.6%（P=0.056）。无治疗组的变化为-8.1%（P=0.24）。两组之间的变化无统计学差异。塞来昔布对凋亡、COX-2、ER 或 PgR 表达没有显著影响。塞来昔布在原发性乳腺癌中仅有适度的生物学效应证据。然而，ER 阳性乳腺癌中 Ki67 减少的趋势需要在更大的患者队列中进一步研究。
