NATIONAL HARBOR, MD. – Use of a combination of bazedoxifene and conjugated estrogens had no significant impact on breast density (a potential risk factor for breast cancer) in postmenopausal women, based on data from the SMART-5 trial.

"Preclinical studies have suggested that the selective estrogen receptor modulator (SERM) bazedoxifene (BZA) prevents estrogen-induced stimulation of breast tissue," said Dr. JoAnn V. Pinkerton of the University of Virginia, Charlottesville. The findings were presented at the annual meeting of the North American Menopause Society.

The Selective Estrogens, Menopause, and Response to Therapy (SMART)-5 study was a 1-year, randomized, double-blind, placebo-controlled, phase III study of healthy postmenopausal women with a uterus who sought treatment for vasomotor symptoms, Dr. Pinkerton said. A subset of 940 women from this study took part in a breast density substudy to assess changes in breast density after a year of treatment with BZA/conjugated estrogens, compared to other treatment or a placebo.

The women underwent mammograms at baseline and again after 1 year of treatment. Changes in breast density were assessed using an analysis of covariance (ANCOVA) model.

After 1 year, the mean adjusted change in breast density from baseline was –0.38% in the women who were received 20 mg BZA/0.45 mg conjugated estrogens, –0.44 in the women who received 20 mg BZA/0.625 conjugated estrogens, –0.24% in the women who received 20 mg BZA alone, 1.60% in the women who received 0.45 mg conjugated estrogens/1.5 mg medroxyprogesterone acetate, and –0.32% in the women who received a placebo.

The only significant difference in breast density either within group or versus placebo occurred in the women who received 0.45 mg conjugated estrogens/1.5 mg medroxyprogesterone acetate.

In addition, BZA 20 mg/CE 0.45 mg and BZA 20 mg/CE 0.625 mg showed noninferiority to placebo for breast density at 1 year, Dr. Pinkerton noted.

Four abnormal mammograms were seen in the 20 mg BZA/0.45 mg conjugated estrogens group, two in the 20 mg BZA/0.625 conjugated estrogens group, one in the 20 mg BZA alone group, three in the 0.45 mg conjugated estrogens/1.5 mg medroxyprogesterone acetate group, and one in the placebo group.

Two cases of breast cancer were reported in the 20 mg BZA/0.45 mg conjugated estrogens group, compared to one case in the 0.45 mg conjugated estrogens/1.5 mg medroxyprogesterone acetate group, one case in the placebo group, and none in the other groups.

The mean age of the women was 54 years, and they were menopausal from 4 to 5 years. Approximately 90% were white. The demographics were similar among all five groups.

Overall, there was no significant difference in the incidence of breast-related adverse events among the groups.

The findings are consistent with those from a previous retrospective study of the SMART-5 data, said Dr. Pinkerton.

"The favorable breast effects seen with BZA 20 mg/CE 0.45 mg and 0.625 mg in this prospective evaluation are a potential advantage of BZA/CE over conventional estrogen/progestin therapy," for postmenopausal women with a uterus, she said.

The study was sponsored by Wyeth Research, now a division of Pfizer, and several of the study coinvestigators are Pfizer employees. Dr. Pinkerton has received fees given to the University of Virginia. She has served as a consultant to Pfizer, Teva, Depomed, and Novo Nordisk, received grants or research support from Pfizer, Depomed, and EndoCeutics, and served on the data safety monitoring board for Boehringer Ingelheim.