Nine RCTs (n=28,632) were included in the review. Four RCTs were considered to be of high quality. Follow-up ranged from 30 to 100 months.
Monotherapy (two RCTs): There was a statistically significant benefit in disease-free survival for aromatase inhibitors compared to tamoxifen over five years (HR 0.89, 95% CI 0.83 to 0.96), but no statistically significant difference in overall survival (HR 0.94, 95% CI 0.82 to 1.08).
Sequenced therapy (four RCTs): There was a statistically significant benefit in overall survival (HR 0.78, 95% CI 0.68 to 0.91) and in relapse-free survival (HR 0.79, 95% CI 0.65 to 0.95).
Extended therapy (three RCTs): There were no statistically significant differences between the groups on any survival outcome.
Adverse events (nine RCTs): There were statistically significant benefits in favour of tamoxifen in fracture risk in monotherapy (RR 1.43, 95% CI 1.26 to 1.62; two RCTs) and sequenced therapy trials (RR 1.36, 95% CI 1.05 to 1.76; three RCTs), but no difference in extended therapy trials. There was a lower risk of endometrial cancer for aromatase inhibitors compared with tamoxifen in monotherapy trials (RR 0.34 95% CI 0.16 to 0.71; two RCTs) and a similar result for endometrial hyperplasia in sequenced therapy trials (RR 0.14, 95% CI 0.04 to 0.51; two RCTs). There were no differences in cardiovascular risk with the exception of thromboembolic events, which were less frequent in monotherapy groups treated with aromatase inhibitors compared with tamoxifen (RR 0.53, 95% CI0.37 to 0.74; two RCTs).
There were no clinically significant differences in quality of life.