[Tamoxifen and aromatase inhibitors in the treatment of breast cancer in menopausal women: pharmacological and clinical aspects].
Estrogen is the main hormone involved in the development and growth of hormone-dependent breast cancer. Endocrine adjuvant treatment in recent years focused primarily on the use of SERMs, mainly tamoxifen. Tamoxifen actions are complex. It acts by competitive antagonism of estrogen at its receptor site. It has beneficial agonistic effects in preventing bone demineralization in postmenopausal women, but a detrimental agonistic effect by increasing the risk of uterine cancer and of thrombo-embolism. However, the situation is changing rapidly with the introduction of recent aromatase inhibitors, which display high specificity towards aromatase. They suppress plasma estrogen levels in postmenopausal women by inhibiting or inactivating aromatase, the enzyme responsible of the synthesis of estrogens from androgenic substrates. A complete estrogen deprivation in target tissues may eventually induce osteoporosis. Unlike tamoxifen, aromatase inhibitors have no partial agonistic action. During the last 20 years, adjuvant tamoxifen treatment for 5 years was the "gold standard" endocrine treatment in postmenopausal women with hormone-receptor-positive breast cancers. A 25% reduction risk of deaths was observed. Recently, the results of clinical trials comparing aromatase inhibitors to tamoxifen in post menopausal women with hormone-dependent breast cancer showed a benefit in favor of aromatase inhibitors in reducing the risk of recurrence. These trials were either comparative (for anastrozole) or sequential (for anastrozole, letrozole and exemestane). The issues of long term adverse effects (bone) and hormone treatment sequence remain to be addressed.
de Cremoux
Patricia
P
Unité de pharmacologie, Institut Curie, 26, rue d'Ulm, 75005 Paris, France.
Diéras
Véronique
V
Poupon
Marie-France
MF
Magdelénat
Henri
H
Sigal-Zafrani
Brigitte
B
Fourquet
Alain
A
Pierga
Jean-Yves
JY
D000077384:Anastrozole; D000730:Androstadienes / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D004965:Estrogen Antagonists / Q000627:therapeutic use; D005260:Female; D006801:Humans; D000077289:Letrozole; D008593:Menopause; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy*; D009570:Nitriles / Q000627:therapeutic use; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use; D013629:Tamoxifen / Q000494:pharmacology / Q000627:therapeutic use*; D014230:Triazoles / Q000627:therapeutic use
D000730:Androstadienes; D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D004965:Estrogen Antagonists; D009570:Nitriles; D020845:Selective Estrogen Receptor Modulators; D014230:Triazoles; D013629:Tamoxifen; D000077384:Anastrozole; D000077289:Letrozole; C056516:exemestane