In a patient-level meta-analysis reported in The Lancet Oncology, researchers from the Early Breast Cancer Trialists’ Collaborative Group found that use of an aromatase inhibitor vs tamoxifen reduced the risk of recurrence in premenopausal women with estrogen receptor (ER)-positive early breast cancer who were receiving ovarian suppression.
Study Details
The study included data from 7,030 women enrolled in four trials (ABCSG XII, SOFT, TEXT, and HOBOE) between June 1999 and August 2015 that compared treatment with an aromatase inhibitor (anastrozole, exemestane, or letrozole; n = 3,528) vs tamoxifen (n = 3,502) for 3 or 5 years, with all women receiving ovarian suppression (goserelin or triptorelin) or ablation. The primary outcome measures were breast cancer recurrence (distant, locoregional, or contralateral), breast cancer mortality, death without recurrence, and all-cause mortality.
Key Findings
Median follow-up was 8.0 years (interquartile range = 6.1–9.3 years).
Risk of breast cancer recurrence was significantly reduced in patients receiving aromatase inhibitors vs tamoxifen (rate ratio [RR] = 0.79, 95% confidence interval [CI] = 0.69–0.90, P = .0005). The main benefit was observed during years 0 to 4 (RR = 0.68, 99% CI = 0.55–0.85, P < .0001), with an absolute reduction of 3.2% (95% CI = 1.8%-4.5%) in 5-year risk (6.9% vs 10.1%). No additional benefit or loss of benefit was observed in years 5 to 9 (RR = 0.98, 99% CI = 0.73–1.33, P = .89) or after year 10. Risk at 10 years was 14.7% vs 17.5%.
Risk of distant recurrence was reduced with aromatase inhibitor treatment (RR = 0.83, 95% CI = 0.71–0.97, P = .018). Rates at 5 and 10 years were 5.6% vs 7.1% and 10.2% vs 12.1%.
No significant differences were observed between aromatase inhibitor vs tamoxifen treatment for:
- Breast cancer mortality (RR = 1.01, 95% CI = 0.82–1.24, P = .94), with 5- and 10-year rates of 3.0% vs 2.4% and 7.2% vs 6.8%
- Death without recurrence (RR = 1.30, 95% CI = 0.75–2.25, P = .34)
- All-cause mortality (RR = 1.04, 95% CI = 0.86–1.27, P = .68), with 5- and 10-year rates of 3.4% vs 2.6% and 8.2% vs 8.0%.
Non–breast cancer deaths occurred in 30 patients (0.9%) vs 24 patients (0.7%; RR = 1.30, 95% CI = 0.75–2.25, P = .36). Endometrial cancer occurred in 7 patients (0.2%) vs 15 patients (0.3%; RR = 0.52, 95% CI = 0.22–1.23, P = .14).
Bone fractures occurred in 227 patients (6.4%) receiving aromatase inhibitors vs 180 patients (5.1%) receiving tamoxifen (RR = 1.27, 95% CI = 1.04–1.54, P = .017).
The investigators concluded, “Using an aromatase inhibitor rather than tamoxifen in premenopausal women receiving ovarian suppression reduces the risk of breast cancer recurrence. Longer follow-up is needed to assess any impact on breast cancer mortality.”
The EBCTCG Secretariat, Clinical Trial Service Unit, Nuffield Department of Population Health, Oxford, is the corresponding entity for The Lancet Oncology article.
Disclosure: For full disclosures of the study authors, visit thelancet.com.
