Purpose of review <p>In a narrative review of randomized clinical trial evidence two major questions regarding menopausal hormone therapy use are addressed. First, do both estrogen-alone and estrogen plus progestin increase breast cancer incidence? Second, in younger postmenopausal women, are there differences in the risk/benefit balance of estrogen-alone versus estrogen plus progestin use which require clinical recognition?</p> Recent Findings <p>Findings from the two Women’s Health Initiative (WHI) randomized, placebo controlled clinical trials evaluating menopausal hormone therapy and breast cancer in postmenopausal women, and from a meta-analysis of other randomized clinical trials evaluating estrogen-alone and breast cancer are summarized and placed in clinical practice context. Relatively short-term, 5.6-year (median) estrogen (as conjugated equine estrogen [CEE]) plus progestin (as medroxy progesterone acetate [MPA]) significantly increases breast cancer incidence through 20-years follow-up. CEE-alone use for 7.2-years (median) significantly decreases breast cancer incidence and significantly decreases breast cancer mortality by 40% through 20-year follow-up. A meta-analysis of 10 randomized trials supports the estrogen-alone effect in reducing breast cancer incidence.</p> Summary <p>Randomized clinical trial evidence supports a significantly reduced breast cancer incidence and breast cancer mortality with estrogen-alone use. When considered for vasomotor symptom management in younger postmenopausal women, estrogen plus progestin has a less favorable risk/benefit profile than estrogen-alone which warrants clinical recognition.</p>