A patient-level meta-analysis of randomized trials 1 compared aromatase inhibitors (anastrozole, exemestane, or letrozole) vs tamoxifen for 3 or 5 years in premenopausal women with ER-positive breast cancer receiving ovarian suppression (goserelin or triptorelin) or ablation. 7030 women were included, and median follow-up was 8.0 years. The rate of breast cancer recurrence was lower for women allocated to an aromatase inhibitor than for women assigned to tamoxifen (RR 0.79, 95% CI 0.69 to 0.90, p=0.0005). The main benefit was seen in years 0-4 (RR 0.68, 99% CI 0.55 to 0.85; p<0.0001), the period when treatments differed, with a 3.2% (95% CI 1.8 to 4.5) absolute reduction in 5-year recurrence risk (6.9% vs 10.1%). There was no further benefit, or loss of benefit, in years 5-9 (RR 0.98, 99% CI 0.73 to 1.33, p=0.89) or beyond year 10. Distant recurrence was reduced with aromatase inhibitor. No significant differences were observed between treatments for breast cancer mortality (RR 1.01, 95% CI 0.82 to 1.24), death without recurrence (1.30, 0.75 to 2.25), or all-cause mortality (1.04, 0.86 to 1.27). There were more bone fractures with aromatase inhibitor than with tamoxifen (RR 1.27, 95% CI 1.04 to 1.54).
A trial-level meta-analysis 4 comparing aromatase inhibitors vs tamoxifen in patients with HR+/HER2- early breast cancer included 5 RCTs. In the base-case analysis, DFS significantly favored AI ± ovarian function suppression (OFS) vs TAM ± OFS (pooled hazard ratio, 0.68; 95 % CI 0.61 to 0.76; P < .0001). Results from scenario analyses were consistent with the base case; premenopausal (pooled hazard ratio, 0.65; 95 % CI 0.56 to 0.76; P < .0001), and postmenopausal (pooled hazard ratio, 0.72; 95 % CI 0.61 to 0.86; P = .001) RCTs favored AI ± OFS over TAM ± OFS.
A multicentre RCT 3 included 3 066 premenopausal women with early breast cancer, who were assigned, stratified according to prior receipt or nonreceipt of chemotherapy, to receive 5 years of tamoxifen, tamoxifen plus ovarian suppression, or exemestane plus ovarian suppression. After a median follow-up of 67 months, the estimated disease-free survival rate at 5 years was 86.6% in the tamoxifen-ovarian suppression group and 84.7% in the tamoxifen group (hazard ratio for disease recurrence, second invasive cancer, or death, 0.83; 95% CI, 0.66 to 1.04; P=0.10). Multivariable allowance for prognostic factors suggested a greater treatment effect with tamoxifen plus ovarian suppression than with tamoxifen alone (HR 0.78; 95% CI, 0.62 to 0.98). Most recurrences occurred in patients who had received prior chemotherapy, among whom the rate of freedom from breast cancer at 5 years was 82.5% in the tamoxifen-ovarian suppression group and 78.0% in the tamoxifen group (HR for recurrence, 0.78; 95% CI, 0.60 to 1.02). At 5 years, the rate of freedom from breast cancer was 85.7% in the exemestane-ovarian suppression group (HRo for recurrence vs. tamoxifen, 0.65; 95% CI, 0.49 to 0.87).
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