TY - JOUR
T1 - Luteinizing hormone-releasing hormone agonists in premenopausal hormone receptor-positive breast cancer
AU - Tan, Sing Huang
AU - Wolff, Antonio C.
PY - 2007/2
Y1 - 2007/2
N2 - Ovarian function suppression for the treatment of premenopausal breast cancer was first used in the late 19th century. Traditionally, ovarian function suppression had been accomplished irreversibly via irradiation or surgery, but analogues of the luteinizing hormone-releasing hormone (LH-RH) have emerged as reliable and reversible agents for this purpose, especially the LH-RH agonists. Luteinizing hormone-releasing hormone antagonists are in earlier stages of development in breast cancer and are not currently in clinical use. Luteinizing hormone-releasing hormone agonists act by pituitary desensitization and receptor downregulation, thereby suppressing gonadotrophin release. Limited information is available comparing the efficacies of the depot preparations of various agonists, but pharmacodynamic studies have shown comparable suppressive capabilities on estradiol and luteinizing hormone. At present, only monthly goserelin is Food and Drug Administration-approved for the treatment of estrogen receptor-positive, premenopausal metastatic breast cancer in the United States. Luteinizing hormone-releasing hormone agonists have proven to be as effective as surgical oophorectomy in premenopausal advanced breast cancer. They offer similar outcomes compared with tamoxifen, but the endocrine combination appears to be more effective than LH-RH agonists alone. In the adjuvant setting, LH-RH agonists versus no therapy reduce the annual odds of recurrence and death in women aged > 50 years with estrogen receptor-positive tumors. Luteinizing hormone-releasing hormone agonists alone or in combination with tamoxifen have shown disease-free survival rates similar to chemotherapy with CMF (cyclophosphamide/methotrexate/5-fluorouracil). Outcomes of chemotherapy with or without LH-RH agonists are comparable, though a few trials favor the combination in young premenopausal women (aged < 40 years). Adjuvant LH-RH agonists with or without tamoxifen might be as efficacious as tamoxifen alone, and the additional benefit from chemotherapy is unclear. Adequately powered studies are now studying the relative merits of combining adjuvant tamoxifen or aromatase inhibitors with ovarian function suppression, the additional benefits of adding ovarian function suppression to chemotherapy, and the need for adjuvant chemotherapy for women treated with combined ovarian function suppression and anti-estrogen therapy.
AB - Ovarian function suppression for the treatment of premenopausal breast cancer was first used in the late 19th century. Traditionally, ovarian function suppression had been accomplished irreversibly via irradiation or surgery, but analogues of the luteinizing hormone-releasing hormone (LH-RH) have emerged as reliable and reversible agents for this purpose, especially the LH-RH agonists. Luteinizing hormone-releasing hormone antagonists are in earlier stages of development in breast cancer and are not currently in clinical use. Luteinizing hormone-releasing hormone agonists act by pituitary desensitization and receptor downregulation, thereby suppressing gonadotrophin release. Limited information is available comparing the efficacies of the depot preparations of various agonists, but pharmacodynamic studies have shown comparable suppressive capabilities on estradiol and luteinizing hormone. At present, only monthly goserelin is Food and Drug Administration-approved for the treatment of estrogen receptor-positive, premenopausal metastatic breast cancer in the United States. Luteinizing hormone-releasing hormone agonists have proven to be as effective as surgical oophorectomy in premenopausal advanced breast cancer. They offer similar outcomes compared with tamoxifen, but the endocrine combination appears to be more effective than LH-RH agonists alone. In the adjuvant setting, LH-RH agonists versus no therapy reduce the annual odds of recurrence and death in women aged > 50 years with estrogen receptor-positive tumors. Luteinizing hormone-releasing hormone agonists alone or in combination with tamoxifen have shown disease-free survival rates similar to chemotherapy with CMF (cyclophosphamide/methotrexate/5-fluorouracil). Outcomes of chemotherapy with or without LH-RH agonists are comparable, though a few trials favor the combination in young premenopausal women (aged < 40 years). Adjuvant LH-RH agonists with or without tamoxifen might be as efficacious as tamoxifen alone, and the additional benefit from chemotherapy is unclear. Adequately powered studies are now studying the relative merits of combining adjuvant tamoxifen or aromatase inhibitors with ovarian function suppression, the additional benefits of adding ovarian function suppression to chemotherapy, and the need for adjuvant chemotherapy for women treated with combined ovarian function suppression and anti-estrogen therapy.
KW - Aromatase inhibitors
KW - Gonadotrophins
KW - Leuprolide
KW - Oophorectomy
KW - Tamoxifen
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U2 - 10.3816/CBC.2007.n.002
DO - 10.3816/CBC.2007.n.002
M3 - Review article
C2 - 17386122
AN - SCOPUS:33947258448
SN - 1526-8209
VL - 7
SP - 455
EP - 464
JO - Clinical Breast Cancer
JF - Clinical Breast Cancer
IS - 6
ER -