Letrozole in the extended adjuvant setting: MA.17.

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.
AuthorsPaul E Goss
JournalBreast cancer research and treatment (Breast Cancer Res Treat) Vol. 105 Suppl 1 Pg. 45-53 ( 2007) ISSN: 0167-6806 [Print] Netherlands
PMID17912635 (Publication Type: Journal Article, Randomized Controlled Trial)
Chemical References
  • Antineoplastic Agents, Hormonal
  • Aromatase Inhibitors
  • Nitriles
  • Receptors, Estrogen
  • Triazoles
  • Tamoxifen
  • letrozole
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Hormonal (administration & dosage)
  • Aromatase Inhibitors (administration & dosage)
  • Breast Neoplasms (drug therapy, mortality)
  • Chemotherapy, Adjuvant
  • Cross-Over Studies
  • Disease-Free Survival
  • Drug Administration Schedule
  • Female
  • Humans
  • Middle Aged
  • Neoplasm Recurrence, Local (prevention & control)
  • Neoplasms, Hormone-Dependent (drug therapy, mortality)
  • Nitriles (administration & dosage)
  • Quality of Life
  • Receptors, Estrogen (drug effects)
  • Tamoxifen (administration & dosage)
  • Treatment Outcome
  • Triazoles (administration & dosage)

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