title: Letrozole in the treatment of breast cancer.
abstract: Endocrine therapy, predominantly using the antioestrogen tamoxifen, has long been a key treatment strategy for oestrogen receptor-positive breast cancer. An alternative approach is to treat patients with aromatase inhibitors, which suppress oestrogen biosynthesis. Letrozole, and other third-generation aromatase inhibitors, are highly specific and potent inhibitors of oestrogen production, which markedly reduce circulating oestrogen levels and whole-body aromatisation of androgen precursors after menopause. In postmenopausal women with hormone receptor-positive or receptor-unknown breast cancer, letrozole has been shown to be superior to megestrol acetate and aminoglutethimide in second-line treatment for advanced breast cancer. Letrozole was also superior to tamoxifen in first-line treatment for advanced breast cancer, as well as in systemic preoperative (neoadjuvant) treatment of locally advanced breast cancer. A recent adjuvant trial demonstrated significant superiority of letrozole over tamoxifen in disease-free survival, and another trial demonstrated that treatment for early breast cancer with letrozole, following 5 years of adjuvant tamoxifen (extended adjuvant therapy), significantly improved disease-free survival compared with placebo, irrespective of nodal status. Ongoing trials will determine whether the optimal use of letrozole in the adjuvant therapy of early breast cancer is as a replacement for tamoxifen, or sequenced additionally before or after tamoxifen.
authors: Department of Oncology, Rigshospitalet, 9 Blegdamsvej, Copenhagen, DK-2100, Denmark. hmouridsen@rh.dk
authors: Henning T
authors: HT
authors: Mouridsen
authors: Ajay S
authors: AS
authors: Bhatnagar
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D047072:Aromatase Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D005260:Female; D006801:Humans; D000077289:Letrozole; D008958:Models, Molecular; D009570:Nitriles / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014230:Triazoles / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D009570:Nitriles; D014230:Triazoles; D000077289:Letrozole