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.