Selective oestrogen receptor modulators in prevention of breast cancer: an updated meta-analysis of individual participant data.
Level 1 - systematic review of randomized trials
Individual participant data meta-analysis of randomized controlled trials
PubMed 23639488 · doi:10.1016/S0140-6736(13)60140-3
What was done
An individual participant data meta-analysis was conducted across nine randomized prevention trials evaluating four selective oestrogen receptor modulators (SERMs: tamoxifen, raloxifene, arzoxifene, and lasofoxifene) versus placebo (or tamoxifen in one trial). The primary endpoint was incidence of all breast cancer (including ductal carcinoma in situ) over a 10-year follow-up period, analyzed by intention to treat.
What was found
Among 83,399 women (306,617 women-years, median follow-up 65 months), SERMs reduced overall breast cancer incidence by 38% (HR 0.62, 95% CI 0.56–0.69), requiring 42 women to be treated to prevent one case in 10 years. The reduction was 42% in years 0–5 (HR 0.58, 95% CI 0.51–0.66; p<0.0001) and 25% in years 5–10 (HR 0.75, 95% CI 0.61–0.93; p=0.007). Invasive ER-positive breast cancer incidence remained reduced for at least 5 years post-completion. Thromboembolic events were significantly increased across SERMs (OR 1.73, 95% CI 1.47–2.05; p<0.0001). Vertebral fractures were reduced by 34% (OR 0.66, 95% CI 0.59–0.73), with a smaller effect on non-vertebral fractures (OR 0.93, 95% CI 0.87–0.99).
Why it matters
This study confirms that preventive SERM therapy produces a durable reduction in ER-positive breast cancer incidence that extends years after completing treatment, defining the absolute benefit and the trade-off against thromboembolic risk.
Limits
The abstract pools multiple distinct SERMs with differing pharmacological profiles and does not report overall mortality or cause-specific mortality. Median follow-up was 65 months, limiting empirical observation beyond the 10-year window, and protection is largely restricted to ER-positive disease.