title: Letrozole in the extended adjuvant setting: MA.17.
abstract: Relapse after completing adjuvant tamoxifen therapy is a persistent threat for women with hormone-responsive breast cancer. Third-generation aromatase inhibitors, such as letrozole, provide a new option for extended adjuvant hormonal therapy after 5 years of tamoxifen. MA.17 was conducted to determine whether letrozole improves outcome after discontinuation of tamoxifen. Postmenopausal women with hormone receptor-positive breast cancer (N=5,187) were randomized to letrozole 2.5 mg or placebo once daily for 5 years. At a median follow-up of 30 months, letrozole significantly improved disease-free survival (DFS; P<0.001), the primary end point, compared with placebo (hazard ratio [HR] for recurrence or contralateral breast cancer 0.58; 95% confidence interval [CI] 0.45, 0.76] P<0.001). Furthermore, letrozole significantly improved distant DFS (HR=0.60; 95% CI 0.43, 0.84; P=0.002) and, in women with node-positive tumors, overall survival (HR=0.61; 95% CI 0.38, 0.98; P=0.04). Clinical benefits, including an overall survival advantage, were also seen in women who crossed over from placebo to letrozole after unblinding, indicating that tumors remain sensitive to hormone therapy despite a prolonged period since discontinuation of tamoxifen. The efficacy and safety of letrozole therapy beyond 5 years is being assessed in a re-randomization study, following the emergence of new data suggesting that clinical benefit correlates with the duration of letrozole. MA.17 showed that letrozole is extremely well-tolerated relative to placebo. Letrozole should be considered for all women completing tamoxifen; new results from the post-unblinding analysis suggest that letrozole treatment should also be considered for all disease-free women for periods up to 5 years following completion of adjuvant tamoxifen.
authors.affiliation: Massachusetts General Hospital Cancer Center, 55 Fruit Street, Cox Bldg., Room 640, Boston, MA 02114, USA. pgoss@partners.org
authors.forename: Paul E
authors.initials: PE
authors.lastname: Goss
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D047072:Aromatase Inhibitors / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D018592:Cross-Over Studies; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077289:Letrozole; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000401:mortality; D009570:Nitriles / Q000008:administration & dosage*; D011788:Quality of Life; D011960:Receptors, Estrogen / Q000187:drug effects; D013629:Tamoxifen / Q000008:administration & dosage*; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D009570:Nitriles; D011960:Receptors, Estrogen; D014230:Triazoles; D013629:Tamoxifen; D000077289:Letrozole