In a patient-level meta-analysis reported in The Lancet, Braybrooke et al of the Early Breast Cancer Trialists’ Collaborative Group found that adding subsequent years of aromatase inhibitor treatment (AIT) for women with early estrogen receptor–positive breast cancer who had already received 5 years of endocrine therapy reduced the risk of recurrence and distant recurrence despite notable nonadherence.
Study Details
The analysis included data from 22,031 women from 12 randomized trials of aromatase inhibitors comparing subsequent AIT vs no further endocrine therapy. Patients had completed at least 5 years of tamoxifen, AIT, or tamoxifen then AIT.
Key Findings
Receipt of subsequent AIT vs no further treatment was associated with a significant reduction in recurrence rates (rate ratio [RR] = 0.73, 95% confidence interval [CI] = 0.67–0.80, P < .0001). Reductions in recurrence were greater after previous tamoxifen alone vs after some previous AIT and in trials of 5 years of AIT vs no further AIT than in trials of 2 to 3 years of AIT vs no further AIT.
After some previous AIT, allocation to 5 further years of AIT was associated with reduced risk of both recurrence (RR = 0.71, 95% CI = 0.61–0.81, P < .0001; risk from year 5 to 15 after diagnosis = 11.6% vs 15.2%) and distant recurrence (RR = 0.73, 95% CI = 0.61–0.88, P = .0010; risk from year 5 to 15 after diagnosis = 6.6% vs 8.6%). A nonsignificant reduction in breast cancer mortality was observed (RR = 0.90, 95% CI = 0.70–1.15, P = .40; 4.4% vs 5.0%). The absolute reduction in recurrence with 10 vs 5 years of AIT was greater among node-positive patients (16.3% vs 20.1%) than for those with node-negative disease (9.1% vs 11.8%).
However, allocation to 5 subsequent years of AIT increased 5-year bone fracture risk (RR = 1.35, 95% CI = 1.13–1.61, P = .0009; 4.6% vs 3.4%). Considerable nonadherence to allocated treatment was also observed—eg, 39.0% for further AIT vs 37.6% for placebo in placebo-controlled trials.
The investigators concluded: “Allocation to 5 further years of AIT reduced subsequent distant recurrence rates by about a quarter despite substantial nonadherence. Longer follow-up would have been needed to help assess directly any effects on mortality.”
Disclosure: The study was funded by Cancer Research UK and Breast Cancer Research Foundation. For full disclosures of all study authors, visit thelancet.com.
