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

Rowan T. Chlebowski, Susan L. Hendrix, Robert D. Langer, Marcia L. Stefanick, Margery Gass, Dorothy Lane, Rebecca J. Rodabough, Mary Ann Gilligan, Michele G. Cyr, Cynthia Thomson, Janardan Khandekar, Helen Petrovitch, Anne McTiernan

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Abstract

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, 16608 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.

Original languageEnglish (US)
Pages (from-to)3243-3253
Number of pages11
JournalJournal of the American Medical Association
Volume289
Issue number24
DOIs
StatePublished - Jun 25 2003

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Women's Health
Progestins
Mammography
Estrogens
Breast Neoplasms
Placebos
Hormones
Conjugated (USP) Estrogens
Medroxyprogesterone Acetate
Uterus
Histology
Breast
Outcome Assessment (Health Care)
Health

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Influence of Estrogen Plus Progestin on Breast Cancer and Mammography in Healthy Postmenopausal Women : The Women's Health Initiative Randomized Trial. / Chlebowski, Rowan T.; Hendrix, Susan L.; Langer, Robert D.; Stefanick, Marcia L.; Gass, Margery; Lane, Dorothy; Rodabough, Rebecca J.; Gilligan, Mary Ann; Cyr, Michele G.; Thomson, Cynthia; Khandekar, Janardan; Petrovitch, Helen; McTiernan, Anne.

In: Journal of the American Medical Association, Vol. 289, No. 24, 25.06.2003, p. 3243-3253.

Research output: Contribution to journalArticle

Chlebowski, RT, Hendrix, SL, Langer, RD, Stefanick, ML, Gass, M, Lane, D, Rodabough, RJ, Gilligan, MA, Cyr, MG, Thomson, C, Khandekar, J, Petrovitch, H & McTiernan, A 2003, 'Influence of Estrogen Plus Progestin on Breast Cancer and Mammography in Healthy Postmenopausal Women: The Women's Health Initiative Randomized Trial', Journal of the American Medical Association, vol. 289, no. 24, pp. 3243-3253. https://doi.org/10.1001/jama.289.24.3243
Chlebowski, Rowan T. ; Hendrix, Susan L. ; Langer, Robert D. ; Stefanick, Marcia L. ; Gass, Margery ; Lane, Dorothy ; Rodabough, Rebecca J. ; Gilligan, Mary Ann ; Cyr, Michele G. ; Thomson, Cynthia ; Khandekar, Janardan ; Petrovitch, Helen ; McTiernan, Anne. / Influence of Estrogen Plus Progestin on Breast Cancer and Mammography in Healthy Postmenopausal Women : The Women's Health Initiative Randomized Trial. In: Journal of the American Medical Association. 2003 ; Vol. 289, No. 24. pp. 3243-3253.
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abstract = "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, 16608 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.",
author = "Chlebowski, {Rowan T.} and Hendrix, {Susan L.} and Langer, {Robert D.} and Stefanick, {Marcia L.} and Margery Gass and Dorothy Lane and Rodabough, {Rebecca J.} and Gilligan, {Mary Ann} and Cyr, {Michele G.} and Cynthia Thomson and Janardan Khandekar and Helen Petrovitch and Anne McTiernan",
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T2 - The Women's Health Initiative Randomized Trial

AU - Chlebowski, Rowan T.

AU - Hendrix, Susan L.

AU - Langer, Robert D.

AU - Stefanick, Marcia L.

AU - Gass, Margery

AU - Lane, Dorothy

AU - Rodabough, Rebecca J.

AU - Gilligan, Mary Ann

AU - Cyr, Michele G.

AU - Thomson, Cynthia

AU - Khandekar, Janardan

AU - Petrovitch, Helen

AU - McTiernan, Anne

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N2 - 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, 16608 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.

AB - 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, 16608 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.

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