Influence of Estrogen Plus Progestin on Breast Cancer and Mammography in Healthy Postmenopausal Women: The Women's Health Initiative Randomized Trial

Context  The Women's Health Initiative trial of combined estrogen plus progestin was stopped early when overall health risks, including invasive breast cancer, exceeded benefits. Outstanding issues not previously addressed include characteristics of breast cancers observed among women using hormones and whether diagnosis may be influenced by hormone effects on mammography.

Objective  To determine the relationship among estrogen plus progestin use, breast cancer characteristics, and mammography recommendations.

Design, Setting, and Participants  Following a comprehensive breast cancer risk assessment, 16 608 postmenopausal women aged 50 to 79 years with an intact uterus were randomly assigned to receive combined conjugated equine estrogens (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) or placebo from 1993 to 1998 at 40 clinical centers. Screening mammography and clinical breast examinations were performed at baseline and yearly thereafter.

Main Outcome Measures  Breast cancer number and characteristics, and frequency of abnormal mammograms by estrogen plus progestin exposure.

Results  In intent-to-treat analyses, estrogen plus progestin increased total (245 vs 185 cases; hazard ratio [HR], 1.24; weighted P<.001) and invasive (199 vs 150 cases; HR, 1.24; weighted P = .003) breast cancers compared with placebo. The invasive breast cancers diagnosed in the estrogen plus progestin group were similar in histology and grade but were larger (mean [SD], 1.7 cm [1.1] vs 1.5 cm [0.9], respectively; P = .04) and were at more advanced stage (regional/metastatic 25.4% vs 16.0%, respectively; P = .04) compared with those diagnosed in the placebo group.

After 1 year, the percentage of women with abnormal mammograms was substantially greater in the estrogen plus progestin group (716 [9.4%] of 7656) compared with placebo group (398 [5.4%] of 7310; P<.001), a pattern which continued for the study duration.

Conclusions  Relatively short-term combined estrogen plus progestin use increases incident breast cancers, which are diagnosed at a more advanced stage compared with placebo use, and also substantially increases the percentage of women with abnormal mammograms. These results suggest estrogen plus progestin may stimulate breast cancer growth and hinder breast cancer diagnosis.
[JAMA, Vol. 289 No. 24, June 25, 2003, Rowan T. Chlebowski, MD, PhD; Susan L. Hendrix, DO; Robert D. Langer, MD, MPH; Marcia L. Stefanick, PhD; Margery Gass, MD; Dorothy Lane, MD, MPH; Rebecca J. Rodabough, MS; Mary Ann Gilligan, MD, MPH; Michele G. Cyr, MD; Cynthia A. Thomson, PhD, RD; Janardan Khandekar, MD; Helen Petrovitch, MD; Anne McTiernan, MD , PhD; for the WHI Investigators
JAMA. 2003;289:3243-3253.
http://jama.ama-assn.org/cgi/content/abstract/289/24/3243?maxtoshow=&hits=10&RESULTFORMAT=&fulltext=Hormone+Therapy+Use+by+Postmenopausal+Women+Associated+With+Increased+Incidence+of+++More+Advanced+Breast+Cancer&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT]

A Prospective Study of Female Hormone Use and Breast Cancer Among Black Women

Background  Epidemiologic studies, largely of white women, have found that recent long-term female hormone use, particularly use of estrogen with progestin, is associated with an increased risk of breast cancer. Some studies suggest that the increase is greater among leaner women. Our aim was to assess the relation of female hormone use to incidence of breast cancer in black women, with attention to differences in effect according to body mass index.

Methods  Data on female hormone use, breast cancer risk factors, and the occurrence of breast cancer were collected through biennial questionnaires from 1995 through 2003 in the Black Women's Health Study, a follow-up study of US black women. During 182 629 person-years of follow-up of 32 559 women 40 years or older, 615 cases of breast cancer were reported.

Results  The incidence rate ratio for breast cancer in women recently using female hormone supplements relative to those who had never used female hormones, with control for confounding factors, increased with duration of use and was 1.58 (95% confidence interval [CI], 1.12-2.23) for 10 or more years of use; the incidence rate ratios were 1.41 (95% CI, 0.95-2.10) for 10 or more years of use of estrogen alone, and 1.45 (95% CI, 0.94-2.23) for 5 or more years of use of estrogen with progestin.

The association of breast cancer with female hormone use was stronger among leaner women (body mass index [calculated as weight in kilograms divided by the square of height in meters] <25) than among heavier women. Among the leaner women who recently used female hormone supplements for durations of 10 or more years, the incidence rate ratio was 3.08 (95% CI, 1.70-5.56); the corresponding estimates among women with body mass indexes of 25 to 29 and 30 or greater were 1.43 and 0.91, respectively, and neither was statistically significant.

Conclusion  These results based on data from US black women strengthen the evidence that use of estrogen alone and estrogen with progestin increases the risk of breast cancer and that the association is stronger among leaner women.

[JAMA, Vol. 166 No. 7, April 10, 2006, Lynn Rosenberg, ScD; Julie R. Palmer, ScD; Lauren A. Wise, ScD; Lucile L. Adams-Campbell, PhD; Arch Intern Med. 2006;166:760-765.http://archinte.ama-assn.org/cgi/content/abstract/166/7/760?maxtoshow=&hits=10&RESULTFORMAT=&fulltext=Hormone+Therapy+Use+by+Postmenopausal+Women+Associated+With+Increased+Incidence+of+++More+Advanced+Breast+Cancer&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT]

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