Copyright @ 2009 The North American Menopause Society. Unauthorized reproduction of this article is prohibited. Menopause: The Journal of The North American Menopause Society Vol. 16, No. 6, pp. 1193/1196 DOI: 10.1097/gme.0b013e3181a7fb1e * 2009 by The North American Menopause Society The effects of bazedoxifene on mammographic breast density in postmenopausal women with osteoporosis Jennifer A. Harvey, MD, 1 Mary K. Holm, MD, 2 Radhika Ranganath, MD, 3 Paul A. Guse, PhD, 3 Edward A. Trott, MD, 3 and Eileen Helzner, MD 3 Abstract Objective: This study aimed to assess quantitative changes in mammographic breast density after 24 months of therapy with bazedoxifene compared with raloxifene or placebo in postmenopausal women with osteoporosis. Methods: This was a retrospective, ancillary study of a subset of women enrolled in a multicenter, double-blind, randomized, placebo- and active-controlled phase 3 trial evaluating bazedoxifene for the treatment of post- menopausal osteoporosis. Participants were randomly assigned to receive bazedoxifene 20 or 40 mg, raloxifene 60 mg, or placebo once daily for 3 years. To be eligible for breast density evaluation, participants had to be 62 years or younger and completed 24 months of treatment, with mammograms at baseline and 24 months. Original mammogram pairs (left craniocaudal views) for each participant were digitized and analyzed by a radi- ologist. Breast density was measured using interactive thresholding to segment the mammogram, and percent density was determined using a validated software program. Results: Mammogram pairs were obtained from 444 participants. Baseline and demographic characteristics were similar among groups (mean age, 58.7 y). After 24 months, the mean percent changes in breast density from baseline were low (bazedoxifene 20 mg, j1.2%; bazedoxifene 40 mg, j0.4%; raloxifene 60 mg, j0.5%; placebo, j0.2%) and not significantly different among groups. Conclusions: Treatment with bazedoxifene for 2 years did not affect age-related changes in breast density in this population of postmenopausal women with osteoporosis. The changes in breast density with bazedoxifene 20 or 40 mg were similar to those with raloxifene 60 mg or placebo. Key Words: Bazedoxifene Y SERMs Y Mammography Y Breast density Y Osteoporosis. H igh intrinsic (nonpharmacological) mammographic breast density has been reported to be a moderate independent risk factor for breast cancer. 1<4 Spe- cifically, the risk of breast cancer is increased fourfold to fivefold in women with high breast density compared with women whose breasts are fatty replaced. 5 Increased breast density also reduces the sensitivity and specificity of mam- mography. 1,6 Breast density has been shown to decrease with advancing age. 7 The use of certain pharmacological agents, including hormone therapy (HT) 8<12 and prolactin-releasing drugs (eg, dopamine agonists), 13 has been reported to increase mam- mographic breast density. For example, one study 10 showed that breast density was similar among HT users and nonusers up to age 55 years, at which point it significantly decreased for nonusers, consistent with normal age-related breast den- sity reduction. In contrast, breast density remained at pre- treatment levels for most HT users. In another study, 12 mammographic density was significantly increased in 20% of women receiving estrogen therapy and 40% of women receiving combined estrogen-progestin therapy, whereas no change in breast density was seen among women who did not receive treatment. Selective estrogen-receptor modulators (SERMs) bind to estrogen receptors and, depending on the target tissue, exhibit either estrogen-receptor agonist or antagonist activity. 14 The effect of SERMs on breast density is of clinical interest, given the continued development of these agents for use in post- menopausal women. Studies 15<19 of tamoxifen and raloxifene have shown that these SERMs do not affect mammographic breast density. Findings from a study 17 evaluating the ef- fects of raloxifene, estrogen, and placebo in postmenopausal women demonstrated that after 24 months of treatment, mammographic breast density was decreased in participants receiving raloxifene or placebo (j1.5% and j1.3%, respec- tively), whereas an increase was seen in participants receiv- ing estrogen therapy (+1.2%). In another study 19 of older Received January 19, 2009; revised and accepted March 31, 2009. From the 1 Department of Radiology, University of Virginia, Charlottes- ville, VA; 2 Innovis Health, Dakota Clinic, Ltd, Fargo, ND; and 3 Wyeth Research, Collegeville, PA. Funding/support: This study was sponsored by Wyeth Research, Collegeville, PA. Editorial support for the writing of this manuscript was provided by Bo Choi, PhD, and was funded by Wyeth. Financial disclosure/conflicts of interest: J. Harvey received research support from Wyeth to perform this study. M. Holm has no conflicts of interest. R. Ranganath, P. Guse, E. Trott, and E. Helzner are current employees of Wyeth. Address correspondence to: Jennifer A. Harvey, MD, Department of Radiology, University of Virginia, PO Box 800170, Charlottesville, VA 22908-0170. E-mail: jah7w@virginia.edu Menopause, Vol. 16, No. 6, 2009 1193