Objective: To evaluate the effects of bazedoxifene-conjugated estrogens on mammographic breast density and other breast parameters in nonhysterectomized postmenopausal women enrolled in a randomized, double-blind, placebo-controlled, and active-controlled phase 3 study.
Methods: The 1-year Selective estrogens, Menopause, And Response to Therapy-5 trial estimated the efficacy and safety of bazedoxifene-conjugated estrogens in 1,843 postmenopausal women seeking vasomotor symptom treatment. A substudy enrolled 940 women with technically acceptable digital mammograms at screening and at 1 year. Treatments included bazedoxifene 20 mg and conjugated estrogens 0.45 or 0.625 mg, placebo, bazedoxifene 20 mg, and conjugated estrogens (0.45 mg) and medroxyprogesterone acetate (1.5 mg). Mammograms were centrally read by a single radiologist blinded to treatment and time sequence; percent breast density was determined using validated software. Noninferiority was based on a predefined margin of 1.5% for comparison of adjusted mean differences in breast density at 12 months.
Results: Bazedoxifene 20 mg and conjugated estrogens 0.45 and 0.625 mg demonstrated noninferiority to placebo in breast density. Mammographic breast density decreased from baseline with bazedoxifene 20 mg and conjugated estrogens 0.45 and 0.625 mg and placebo (mean -0.38% and standard error [SE] 0.22%, mean -0.44% and SE 0.22%, mean -0.32% and SE 0.23%, respectively). Conjugated estrogens-medroxyprogesterone acetate significantly increased breast density from baseline (mean 1.60%, SE 0.35%; P<.001) compared with placebo. Both bazedoxifene-conjugated estrogens doses showed rates of breast tenderness similar to placebo and significantly (P<.001) lower than conjugated estrogens-medroxyprogesterone acetate. No differences in incidence of breast-related adverse events were identified.
Conclusion: Bazedoxifene 20 mg and conjugated estrogens 0.45 and 0.625 mg did not increase mammographic breast density or breast tenderness over the course of 1 year with a favorable breast-related safety profile.
Clinical trial registration: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00808132.
Level of evidence: I.