Improved Outcomes With Aromatase Inhibitors vs Tamoxifen in Early Breast Cancer
In a patient-level meta-analysis of randomized trials reported in The Lancet by the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), 5 years of aromatase inhibitor treatment significantly reduced the recurrence risk vs 5 years of tamoxifen therapy during the first 4 years and reduced the 10-year breast cancer mortality vs tamoxifen. In trials in which a comparator group received tamoxifen followed by an aromatase inhibitor, recurrence rates were lower with aromatase inhibitors during the period that treatment differed between groups.
Study Details
The meta-analyses included individual data on 31,920 postmenopausal women with estrogen receptor–positive early breast cancer in randomized trials of 5 years of an aromatase inhibitor vs 5 years of tamoxifen; 5 years of an aromatase inhibitor vs 2 to 3 years of tamoxifen then an aromatase inhibitor to year 5; and 2 to 3 years of tamoxifen then an aromatase inhibitor to year 5 vs 5 years of tamoxifen. Outcomes were analyzed on an intent-to-treat basis stratified by age, nodal status, and trial, yielding aromatase inhibitor vs tamoxifen first-event rate ratios (RRs; P values are two-sided).
Comparison Outcomes
In the comparison of 5 years of an aromatase inhibitor vs 5 years of tamoxifen, recurrence was significantly reduced with aromatase inhibitors during years 0 to 1 (RR = 0.64, 95% confidence interval [CI] = 0.52–0.78) and 2 to 4 (RR = 0.80, 95% CI = 0.68–0.93) and nonsignificantly thereafter. Ten-year breast cancer mortality was 12.1% vs 14.2% (RR = 0.85, P = .009).
In the comparison of 5 years of an aromatase inhibitor vs 2 to 3 years of tamoxifen followed by an aromatase inhibitor to year 5, recurrence was significantly reduced with aromatase inhibitors during years 0 to 1 (RR = 0.74, 95% CI = 0.62–0.89) but not while both groups received aromatase inhibitors during years 2 to 4 or thereafter. In these trials, risk of recurrence was lower with 5 years of aromatase inhibitors vs tamoxifen followed by aromatase inhibitors (RR = 0.90, P = .045), but the reduction in 10-year breast cancer mortality was not significant (RR = 0.89, P = .11).
In the comparison of 2 to 3 years of tamoxifen then an aromatase inhibitor to year 5 vs 5 years of tamoxifen, the risk of recurrence was significantly reduced with aromatase inhibitors during years 2 to 4 (RR = 0.56, 95% CI = 0.46–0.67) but not thereafter. Ten-year breast cancer mortality was lower with switching to aromatase inhibitors vs remaining on tamoxifen (8.7% vs 10.1%, P = .015).
When all three types of comparison were pooled, recurrence was significantly reduced with aromatase inhibitors during periods when treatments differed (RR = 0.70, 95% CI = 0.64–0.77) but not significantly thereafter (RR = 0.93, P = .08). Breast cancer mortality was reduced with aromatase inhibitors when treatments differed (RR = 0.79, 95% CI = 0.67–0.92), subsequently (RR = 0.89, 95% CI = 0.81–0.99), and for all periods combined (RR = 0.86, P = .0005). All-cause mortality was also reduced (RR = 0.88, P = .0003).
Aromatase inhibitor treatment was associated with a reduced risk for endometrial cancers (10-year incidence = 0.4% vs 1.2%, RR = 0.33, 95% CI = 0.21–0.51) and an increased risk of bone fractures (5-year risk = 8.2% vs 5.5%, RR = 1.42, 95% CI = 1.28–1.57).
The investigators concluded: “Aromatase inhibitors reduce recurrence rates by about 30% (proportionately) compared with tamoxifen while treatments differ but not thereafter. Five years of an aromatase inhibitor reduces 10-year breast cancer mortality rates by about 15% compared with 5 years of tamoxifen, hence by about 40% (proportionately) compared with no endocrine treatment.”
The study was funded by Cancer Research UK, Medical Research Council. For full disclosures of the study authors, visit www.thelancet.com.
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