The study findings are based on an analysis of 16,608 postmenopausal women who participated in the Women's Health Initiative clinical trial, from 1993 to 1998. Women were randomly assigned to receive a combination of oestrogen daily (0.625 mg conjugated equine estrogens) plus progesterone daily (2.5 mg medroxyprogesterone acetate) (n = 8,506) or placebo (n = 8,102). Each participant received mammography and a breast examination yearly, with biopsies performed based on the physicians' clinical judgment.

During the 5.6 years of the study, 199 women in the combined hormone therapy group and 150 women in the placebo group developed breast cancer. Abnormal mammography results were more common among women who were taking hormones (35%) compared with women who were assigned to placebo (23%). The women taking hormones also had a 4% greater risk of having an abnormal mammography after 1 year and an 11% greater risk after 5 years.

Breast biopsies also were more common among women taking hormones (10%) compared with those assigned to placebo (6.1%).

"Although breast cancers were significantly increased and were diagnosed at higher stages in the combined hormone group, biopsies in that group less frequently diagnosed cancer (14.8% vs 19.6%)," the authors, led by Rowan T. Chlebowski, MD, PhD, Los Angeles Biomedical Research Institute, Harbor-University of California, Los Angeles, Medical Center, Los Angeles, noted. "After discontinuation of combined hormone therapy, its adverse effect on mammography modulated but remained significantly different from that of placebo for at least 12 months."

The use of combined hormones may increase breast density, which increases the risk of breast cancer and could also delay diagnosis; however, the authors noted that breast density was not measured in this study.

"Use of conjugated equine oestrogens plus medroxyprogesterone acetate for approximately 5 years resulted in more than 1 in 10 and 1 in 25 women having otherwise avoidable mammography abnormalities and breast biopsies, respectively, and compromised the diagnostic performance of both," the authors concluded. "This adverse effect on breast cancer detection should be incorporated into risk-benefit discussions with women considering even short-term combined hormone therapy."

Source: Archives of Internal Medicine, February 25, 2008

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