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Rowan T. Chlebowski, MD, PhD; Garnet Anderson, PhD; Mary Pettinger, MS; Dorothy Lane, MD, MPH; Robert D. Langer, MD, MPH; Mary Ann Gillian, MD, MPH; Brian W. Walsh, MD; Chu Chen, PhD; Anne McTiernan, MD, PhD; for the Women's Health Initiative Investigators

Arch Intern Med. 2008;168(4):370-377.

Background  The effect of combined hormone therapy on breast cancer detection is not established.

Methods  We examined the effect of combined hormone therapy on breast cancer detection in the Women's Health Initiative trial, which randomized 16 608 postmenopausal women to receive conjugated equine estrogens (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) or placebo. Mammography and breast examinations were performed at baseline and annually per protocol, with breast biopsies based on clinical findings. The effects of conjugated equine estrogens plus medroxyprogesterone acetate on breast cancer detection was determined throughout 5.6 years of intervention using receiver operating characteristic analyses to evaluate mammography results.

Results  Conjugated equine estrogens plus medroxyprogesterone acetate increased the cumulative frequency of mammograms with abnormalities vs placebo (35.0% vs 23.0%; P < .001), which had less sensitivity for cancer detection and increased cumulative breast biopsy frequency (10.0% vs 6.1%; P < .001). 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%; P = .006). After discontinuation of combined hormone therapy, its adverse effect on mammograms modulated but remained significantly different from that of placebo for at least 12 months (P < .001).

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

Trial Registration  clinicaltrials.gov Identifier: NCT00000611

Author Affiliations: Los Angeles Biomedical Research Institute at Harbor–UCLA Medical Center, Torrance, California (Dr Chlebowski); Fred Hutchinson Cancer Research Center, Seattle, Washington (Drs Anderson, Chen, and McTiernan and Ms Pettinger); Department of Preventive Medicine, The State University of New York, Stony Brook (Dr Lane); Department of Family and Preventive Medicine, University of San Diego, La Jolla, California (Dr Langer); Department of Medicine, Medical College of Wisconsin, Milwaukee (Dr Gillian); and Center for Reproductive Medicine, Brigham and Women's Hospital, Boston, Massachusetts (Dr Walsh).
Group Information: A full list of the Women's Health Initiative Investigators can be found at http://www.whi.org.

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