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Estrogen Plus Progestin and Breast Cancer Detection by Means of Mammography and Breast Biopsy

26 February 2008

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.

Authors 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.

Comment by Dr Heather Currie
This report is really saying that changes in breast density can occur within the first year of use of this particular type of HRT. Increase in breast density can affect the interpretation of mammograms and therefore in theory, can affect the diagnosis of breast cancer. However, the report is NOT saying that there is an increase in the risk of breast cancer in the first year. Furthermore, the dose of hormones used in this study was higher than the doses frequently used today. There is evidence that different doses, types and route of HRT may not have the same effect.

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