ABSTRACT

Purpose: In the Women’s Health initiative (WHI) randomized clinical trial, conjugated equine estrogen (CEE)-alone signifcantly reduced breast cancer incidence (P=0.005). As cohort studies had opposite fndings, other randomized clinical trials were identifed to conduct a meta-analysis of estrogen-alone infuence on breast cancer incidence.

Methods: We conducted literature searches on randomized trials and: estrogen, hormone therapy, and breast cancer, and searches from a prior meta-analysis and reviews. In the meta-analysis, for trials with published relative risks (RR) and 95% confdence intervals (CI), each log-RR was multiplied by weight=1/V, where V=variance of the log-RR, and V was derived from the corresponding 95% CI. For smaller trials with only breast cancer numbers, the corresponding log-RR=(O – E)/ weight, where O is the observed case number in the oestrogen-alone group and E the corresponding expected case number, E=nP.

Results: Findings from 10 randomized trials included 14,282 participants and 591 incident breast cancers. In 9 smaller trials, with 1.2% (24 of 2029) vs 2.2% (33 of 1514) randomized to estrogen-alone vs placebo (open label, one trial) (RR 0.65 95% CI 0.38–1.11, P=0.12). For 5 trials evaluating estradiol formulations, RR=0.63 95% CI 0.34–1.16, P=0.15. Combining the 10 trials, 3.6% (262 of 7339) vs 4.7% (329 of 6943) randomized to estrogen-alone vs placebo (overall RR 0.77 95% CI 0.65–0.91, P=0.002).

Conclusion: The totality of randomized clinical trial evidence supports a conclusion that estrogen-alone use signifcantly reduces breast cancer incidence.

Keywords: Breast cancer incidence · Estrogen-alone · Randomized trials · Meta-analysis