Mandalà M, Moro C, Ferretti G, Calabro M G, Nolè F, Rocca A, Munzone E, Castro A, Curigliano G
Division of Medical Oncology, European Institute of Oncology, Via Ripamonti 435, 20141-Milan, Italy.
Anticancer Res. 2001 Jan-Feb;21(1B):585-8.
Tamoxifen suppresses insulin-like growth factor-1 (IGF-1) plasma levels in early and advanced breast cancer patients. Relationships between tamoxifen (GH) and IGF-1 are complex and not completely described yet. The present investigation was performed to evaluate the effect of acute and chronic tamoxifen administration on GH response to growth hormone-releasing hormone (GHRH), as well as on IGF-1 serum levels.
Evaluation of GH after administration of GHRH was performed (a) at baseline, (b) 3 hours after 20 mg oral administration of tamoxifen and (c) after 12 weeks of 20 mg a day oral tamoxifen treatment, in fifteen postmenopausal stage I-II breast cancer patients. IGF-I was measured at baseline and after chronic tamoxifen administration.
The GH response to GHRH was significantly reduced after 12 weeks of tamoxifen 10 mg administered twice a day orally (mean peak 3.2 +/- 0.2 micrograms/l, mean AUC 261.3 +/- 18.2 micrograms/minute p < 0.01 versus basal AUC). A concomitant significant reduction of IGF-1 was observed after 3 months of tamoxifen treatment. Basal pretreatment levels of 113.2 +/- 15.5 micrograms/l were suppressed to 70 +/- 7.9 micrograms/l (p < 0.01).
Our study confirm the inhibitory effect of tamoxifen on IGF-I and suggested, as shown in previous in vitro data, that its suppression could be directly related to GH reduction in response to GHRH stimulation.
他莫昔芬可降低早期和晚期乳腺癌患者血浆中胰岛素样生长因子-1(IGF-1)水平。他莫昔芬(GH)与IGF-1之间的关系较为复杂,尚未完全阐明。本研究旨在评估急性和慢性给予他莫昔芬对生长激素释放激素(GHRH)刺激的生长激素(GH)反应以及IGF-1血清水平的影响。
对15例绝经后I-II期乳腺癌患者进行如下检测:(a)基线时;(b)口服20mg他莫昔芬3小时后;(c)口服20mg/天他莫昔芬治疗12周后,给予GHRH后评估GH水平。在基线时和慢性给予他莫昔芬后检测IGF-I水平。
每天口服两次10mg他莫昔芬12周后,对GHRH的GH反应显著降低(平均峰值3.2±0.2μg/l,平均AUC 261.3±18.2μg/分钟,与基础AUC相比p<0.01)。他莫昔芬治疗3个月后,IGF-1水平同时显著降低。预处理基础水平为113.2±15.5μg/l,降至70±7.9μg/l(p<0.01)。
我们的研究证实了他莫昔芬对IGF-I的抑制作用,并如先前体外数据所示,提示其抑制作用可能与GHRH刺激后GH降低直接相关。