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 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. 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.
Four abnormal mammograms were seen in the 20-mg BZA/0.45-mg conjugated estrogens group, two in the 20-mg BZA/0.625-mg 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.
A video with Dr. Pinkerton can be viewed by using the QR code or by visiting www.obgynnews.com
Preclinical studies have suggested that BZA prevents estrogen-induced stimulation of breast tissue.
Source DR. PINKERTON