LH-RH Agonists in the Treatment of Metastatic Breast Cancer: Ten Years’ Experience

Signal Transduction of GnRH Receptor in the Reproductive.

“…[1][2][3][4][5][6][7][8]. GnRH analogs have been used in the treatment of the endocrine-dependent cancers; breast cancer [9][10][11][12][13], prostatic cancer [13][14][15][16][17], pancreatic cancer [18, 191, endometrial cancer [20,21], ovarian stromal tumor [22,23] and ovarian cancer [24][25][26][27][28][29][30][31][32][33][34][35]. The antitumor action of GnRH analog had been presumed to result from a desensitization or down-regulation of GnRH receptors in the pituitary, with a consequent decline in gonadotropin secretion and gonadal hormone production.…”

Induction of apoptosis by AN-152, a cytotoxic analog of luteinizing hormone-releasing hormone (LHRH), in LHRH-R positive human breast cancer cells is independent of multidrug resistance-1 (MDR-1) system

“…The role of these receptors in human breast cancer cells is not yet clear, but agonists and antagonists of LHRH suppress tumor-growth of LHRH-R positive breast cancer cells in vitro and in vivo [4][5][6][7][8][9]. Moriya et al described significant inverse correlation between LHRH-R immunoreactivity and expression of Ki-67, suggesting a LHRH-mediated low proliferative rate in human breast carcinomas [3].…”

Combined Treatment With Buserelin and Tamoxifen in Premenopausal Metastatic Breast Cancer: a Randomized Study

“…Surgical ovariectomy has been used for the last 100 years as treatment for advanced breast cancer in premenopausal patients (11). Phase II studies of medical treatment with tamoxifen (5) or LHRH agonists (14) showed response rates that were similar to those observed after surgical castration. Two randomized studies comparing surgical ovariectomy with tamoxifen (22,23) and two other randomized studies comparing surgical ovariectomy with the LHRH agonist goserelin (19,40) have been reported.…”

“…Although direct antitumor effects of LHRH analogues have been demonstrated in vitro and specific LHRH-binding sites have been found in 52%-67% of primary human breast cancers [for review, see (15)], the main mechanism of action of LHRH analogues is medical castration. The application of depot formulations (long-acting subcutaneous or intramuscular implants) of various LHRH agonists caused long-term suppression of ovarian estrogen secretion (14,(16)(17)(18). A recent randomized study of 138 premenopausal patients with estrogen receptor-positive and progesterone receptor-positive metastatic breast cancer (19) showed that treatment with the LHRH agonist goserelin resulted in failure-free survival and overall survival similar to those observed after ovariectomy.…”