medwireNews: Aromatase inhibitors (AIs) significantly reduce the risk for breast cancer recurrence relative to tamoxifen in premenopausal women treated with ovarian function suppression, suggests a patient-level meta-analysis.
However, this risk reduction did not appear to translate into an improvement in breast cancer-specific mortality, which was comparable between the AI and tamoxifen groups, presenting author Rosie Bradley (University of Oxford, UK) told delegates of the 2021 San Antonio Breast Cancer Symposium.
But she stressed the need for longer follow-up to fully assess the effects on mortality.
The meta-analysis included data on 7030 premenopausal women included in the ABCSG 12, TEXT, SOFT, or HOBOE trials that compared an AI (anastrozole, exemestane, or letrozole) with tamoxifen, both given for 3–5 years, on a background of ovarian suppression with goserelin or triptorelin.
Pooled analysis, with a median follow-up of 8 years, showed that treatment with an AI was associated with a significant 21% reduction in the risk for recurrence (defined as distant, locoregional, or new contralateral breast cancer) compared with tamoxifen.
The cumulative incidence of recurrence at 10 years was 14.7% in the AI group and 17.5% in the tamoxifen group, equating to an absolute risk reduction of 2.8 percentage points with AI treatment.
Bradley pointed out that the greatest benefit of AI over tamoxifen was observed in the first 4 years of treatment, “with no further benefit or loss of benefit in years 5 to 9, and little follow-up beyond year 10.”
Use of an AI also reduced the risk for distant recurrence by a significant 17% relative to tamoxifen. The cumulative 10-year rates of distant recurrence were 10.2% and 12.1%, respectively, and the absolute risk reduction with an AI was 1.9 percentage points
But there was no significant difference in breast cancer-specific mortality risk, with comparable 10-year rates of 6.8% and 7.2% in the AI and tamoxifen groups, respectively.
And AI use was associated with a significant 27% increased risk for bone fractures; the cumulative rate at 5 years was 5.0% among AI-treated participants versus 3.8% among those given tamoxifen.
Bradley presented subgroup analyses that showed no difference in proportional reduction in recurrence with use of an AI versus tamoxifen by age, BMI, tumor size and grade, histologic subtype, or receipt of chemotherapy.
However, the researchers observed “a trend for diminishing efficacy with increasing nodal involvement,” such that there appears to be “no apparent benefit with AI for N4 disease,” a finding that Bradley described as “unanticipated.”
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