Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial.
Level 2 - randomized trial
Individual double-blind randomized controlled trial
PubMed 25497694 · doi:10.1016/S1470-2045(14)71171-4
What was done
In the IBIS-I double-blind randomized controlled trial, 7,154 pre- and postmenopausal women aged 35–70 years at increased risk of breast cancer were randomly assigned (1:1) to oral tamoxifen 20 mg daily (n=3,579) or matching placebo (n=3,575) for 5 years. The primary endpoint was occurrence of breast cancer (invasive breast cancer and ductal carcinoma in situ), analyzed by intention to treat. Extended post-treatment follow-up was analyzed after a median of 16.0 years (IQR 14.1–17.6) using Cox proportional hazards models.
What was found
Breast cancer was reported in 251 (7.0%) of 3,579 women in the tamoxifen group versus 350 (9.8%) of 3,575 women in the placebo group (HR 0.71, 95% CI 0.60–0.83, p < 0.0001). Risk reduction was similar during years 0–10 (163 [4.6%] vs 226 [6.3%]; HR 0.72, 95% CI 0.59–0.88, p = 0.001) and after 10 years (88 [2.6%] in 3,343 women vs 124 [3.8%] in 3,295 women; HR 0.69, 95% CI 0.53–0.91, p = 0.009). The reduction was significant for invasive estrogen receptor (ER)-positive breast cancer (HR 0.66, 95% CI 0.54–0.81, p < 0.0001) and ductal carcinoma in situ (HR 0.65, 95% CI 0.43–1.00, p = 0.05), but no effect was observed for invasive ER-negative breast cancer (HR 1.05, 95% CI 0.71–1.57, p = 0.8).
Why it matters
This study shows that the preventive benefits of a 5-year tamoxifen regimen persist for at least a decade after stopping treatment, improving the long-term benefit-to-harm balance for high-risk women.
Limits
The abstract reports no data on adverse events, drug toxicities, or overall/cause-specific mortality. Tamoxifen showed no protective effect against ER-negative breast cancers. Findings apply specifically to women with elevated baseline breast cancer risk.