This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (92)  • Contact me when this article is cited  Related Content  • Related letter  • Similar articles in JAMA  Topic Collections  • Oncology  • Breast Cancer  • Surgical Interventions  • Urology  • Women's Health, Other  • Randomized Controlled Trial  • Mammography  • Alert me on articles by topic

Marcia L. Stefanick, PhD; Garnet L. Anderson, PhD; Karen L. Margolis, MD, MPH; Susan L. Hendrix, DO; Rebecca J. Rodabough, MS; Electra D. Paskett, PhD; Dorothy S. Lane, MD, MPH; F. Allan Hubbell, MD, MSPH; Annlouise R. Assaf, PhD; Gloria E. Sarto, MD; Robert S. Schenken, MD; Shagufta Yasmeen, MD; Lawrence Lessin, MD; Rowan T. Chlebowski, MD, PhD; for the WHI Investigators

JAMA. 2006;295:1647-1657.

Context  The Women's Health Initiative Estrogen-Aone trial comparing conjugated equine estrogens (CEE) with placebo was stopped early because of an increased stroke incidence and no reduction in risk of coronary heart disease. Preliminary results suggesting possible reduction in breast cancers warranted more detailed analysis.

Objective  To determine the effects of CEE on breast cancers and mammographic findings.

Design, Setting, and Participants  Following breast cancer risk assessment, 10 739 postmenopausal women aged 50 to 79 years with prior hysterectomy were randomized to CEE or placebo at 40 US clinical centers from 1993 through 1998. Mammography screenings and clinical breast examinations were performed at baseline and annually. All breast cancers diagnosed through February 29, 2004, are included.

Intervention  A dose of 0.625 mg/d of CEE or an identical-appearing placebo.

Main Outcome Measures  Breast cancer incidence, tumor characteristics, and mammogram findings.

Results  After a mean (SD) follow-up of 7.1 (1.6) years, the invasive breast cancer hazard ratio (HR) for women assigned to CEE vs placebo was 0.80 (95% confidence interval [CI], 0.62-1.04; P = .09) with annualized rates of 0.28% (104 cases in the CEE group) and 0.34% (133 cases in the placebo group). In exploratory analyses, ductal carcinomas (HR, 0.71; 95% CI, 0.52-0.99) were reduced in the CEE group vs placebo group; however, the test for interaction by tumor type was not significant (P = .054). At 1 year, 9.2% of women in the CEE group had mammograms with abnormalities requiring follow-up vs 5.5% in the placebo group (P<.001), a pattern that continued through the trial to reach a cumulative percentage of 36.2% vs 28.1%, respectively (P<.001); however, this difference was primarily in assessments requiring short interval follow-up.

Conclusions  Treatment with CEE alone for 7.1 years does not increase breast cancer incidence in postmenopausal women with prior hysterectomy. However, treatment with CEE increases the frequency of mammography screening requiring short interval follow-up. Initiation of CEE should be based on consideration of the individual woman's potential risks and benefits.

Trial Registration  clinicaltrials.gov Identifier: NCT00000611

Author Affiliations: Stanford Prevention Research Center, Department of Medicine, Stanford University, Stanford, Calif (Dr Stefanick); Women's Health Initiative Clinical Coordinating Center, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Wash (Dr Anderson and Ms Rodabough); Hennipin County Medical Center, Minneapolis, Minn (Dr Margolis); Department of Obstetrics and Gynecology, Wayne State University School of Medicine/Hutzel Women's Hospital, Detroit, Mich (Dr Hendrix); Division of Epidemiology, School of Public Health, Ohio State University, Columbus (Dr Paskett); Department of Preventive Medicine, State University of New York, Stony Brook (Dr Lane); Department of Medicine, University of California, Irvine (Dr Hubbell); Center for Primary Care and Prevention, Memorial Hospital of Rhode Island, Pawtucket (Dr Assaf); Department of Obstetrics and Gynecology, University of Wisconsin, Madison (Dr Sarto); Department of Obstetrics and Gynecology, University of Texas Health Science Center, San Antonio (Dr Schenken); Department of Obstetrics and Gynecology, University of California, Davis (Dr Yasmeen); Medstar Research Institute, Washington, DC (Dr Lessin); and Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, Calif (Dr Chlebowski).

RELATED LETTER

Hormone Therapy and Cardiovascular Risk
Samuel Shapiro
JAMA. 2007;298(6):623.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

RE: "CONJUGATED EQUINE ESTROGENS AND BREAST CANCER RISK IN THE WOMEN'S HEALTH INITIATIVE CLINICAL TRIAL AND OBSERVATIONAL STUDY"
Shapiro
Am J Epidemiol 2008;168:1213-1213.
FULL TEXT  

Menopausal Hormone Therapy and Breast Cancer Risk in the NIH-AARP Diet and Health Study Cohort
Brinton et al.
Cancer Epidemiol. Biomarkers Prev. 2008;17:3150-3160.
ABSTRACT | FULL TEXT  

Conjugated Equine Estrogens and Colorectal Cancer Incidence and Survival: The Women's Health Initiative Randomized Clinical Trial
Ritenbaugh et al.
Cancer Epidemiol. Biomarkers Prev. 2008;17:2609-2618.
ABSTRACT | FULL TEXT  

Hormone Therapy and the Risk of Breast Cancer in BRCA1 Mutation Carriers
Eisen et al.
JNCI J Natl Cancer Inst 2008;100:1361-1367.
ABSTRACT | FULL TEXT  

Menopausal Hormone Therapy in BRCA1 Mutation Carriers: Uncertainty and Caution
Chlebowski and Prentice
JNCI J Natl Cancer Inst 2008;100:1341-1343.
FULL TEXT  

Re: Conjugated Equine Estrogen and Risk of Benign Proliferative Breast Disease: A Randomized Controlled Trial
Wood and Cline
JNCI J Natl Cancer Inst 2008;100:1335-1335.
FULL TEXT  

Pharmacologic Treatment of Low Bone Density or Osteoporosis to Prevent Fractures: A Clinical Practice Guideline from the American College of Physicians
Qaseem et al.
ANN INTERN MED 2008;149:404-415.
ABSTRACT | FULL TEXT  

Conjugated Equine Estrogens and Breast Cancer Risk in the Women's Health Initiative Clinical Trial and Observational Study
Prentice et al.
Am J Epidemiol 2008;167:1407-1415.
ABSTRACT | FULL TEXT  

HABITS trial results confirmed in two-year follow-up
Brown
Menopause Int 2008;14:48-51.
FULL TEXT  

Osteoporosis: Management and Treatment Strategies for Orthopaedic Surgeons
Gehrig et al.
JBJS 2008;90:1362-1374.
FULL TEXT  

Estrogen Plus Progestin Therapy and Breast Cancer in Recently Postmenopausal Women
Prentice et al.
Am J Epidemiol 2008;167:1207-1216.
ABSTRACT | FULL TEXT  

Conjugated Equine Estrogen and Risk of Benign Proliferative Breast Disease: A Randomized Controlled Trial
Rohan et al.
JNCI J Natl Cancer Inst 2008;100:563-571.
ABSTRACT | FULL TEXT  

Impact of Estrogen Deprivation on Gene Expression Profiles of Normal Postmenopausal Breast Tissue In vivo
Kendall et al.
Cancer Epidemiol. Biomarkers Prev. 2008;17:855-863.
ABSTRACT | FULL TEXT  

Use of Different Postmenopausal Hormone Therapies and Risk of Histology- and Hormone Receptor-Defined Invasive Breast Cancer
Fournier et al.
JCO 2008;26:1260-1268.
ABSTRACT | FULL TEXT  

Hormone Therapy, Dilemmas, Medical Decisions.
Schulkin
J Law Med Ethics 2008;36:73-88.
 

Estrogen Plus Progestin and Breast Cancer Detection by Means of Mammography and Breast Biopsy
Chlebowski et al.
Arch Intern Med 2008;168:370-377.
ABSTRACT | FULL TEXT  

Systematic Review: Comparative Effectiveness of Treatments to Prevent Fractures in Men and Women with Low Bone Density or Osteoporosis
MacLean et al.
ANN INTERN MED 2008;148:197-213.
ABSTRACT | FULL TEXT  

Low-Dose Tamoxifen for Combination Hormone Replacement Therapy Users
Fabian
JCO 2007;25:4162-4164.
FULL TEXT  

Increased incidence of lobular breast cancer in women treated with hormone replacement therapy: implications for diagnosis, surgical and medical treatment
Biglia et al.
Endocr Relat Cancer 2007;14:549-567.
ABSTRACT | FULL TEXT  

Hormone Therapy and Cardiovascular Risk
Shapiro
JAMA 2007;298:623-623.
FULL TEXT  

Main morbidities recorded in the women's international study of long duration oestrogen after menopause (WISDOM): a randomised controlled trial of hormone replacement therapy in postmenopausal women
Vickers et al.
BMJ 2007;335:239-239.
ABSTRACT | FULL TEXT  

Management of cardiovascular risk in the peri-menopausal woman: a consensus statement of European cardiologists and gynaecologists
Collins et al.
Eur Heart J 2007;28:2028-2040.
ABSTRACT | FULL TEXT  

Drospirenone increases endothelial nitric oxide synthesis via a combined action on progesterone and mineralocorticoid receptors
Simoncini et al.
Hum Reprod 2007;22:2325-2334.
ABSTRACT | FULL TEXT  

Critical assessment of new risk factors for breast cancer: considerations for development of an improved risk prediction model
Santen et al.
Endocr Relat Cancer 2007;14:169-187.
ABSTRACT | FULL TEXT  

Menopausal Hormone Therapy: Calculating Risks and Benefits
Gambrell and Natrajan
Obstet Gynecol 2007;109:1455-1455.
FULL TEXT  

Managing the menopause
Roberts
BMJ 2007;334:736-741.
FULL TEXT  

Absence of the proapoptotic Bax protein extends fertility and alleviates age-related health complications in female mice
Perez et al.
Proc. Natl. Acad. Sci. USA 2007;104:5229-5234.
ABSTRACT | FULL TEXT  

Endometrial Effects of Tibolone
Archer et al.
J. Clin. Endocrinol. Metab. 2007;92:911-918.
ABSTRACT | FULL TEXT  

Unopposed Estradiol Therapy in Postmenopausal Women: Results From Two Randomized Trials
Steiner et al.
Obstet Gynecol 2007;109:581-587.
ABSTRACT | FULL TEXT  

Use of Oral Conjugated Estrogen Alone and Risk of Breast Cancer
Zhang et al.
Am J Epidemiol 2007;165:524-529.
ABSTRACT | FULL TEXT  

Putting risk into context
Drife
The Obstetrician and Gynaecologist 2007;9:42-47.
ABSTRACT | FULL TEXT  

Hormones and Breast Cancer: Should Practice Be Changed?
Collins
Obstet Gynecol 2006;108:1352-1353.
FULL TEXT  

Other articles noted
Evid. Based Med. 2006;11:127-128.
FULL TEXT  

Risk-benefit profiles of raloxifene for women.
Stefanick
NEJM 2006;355:190-192.
FULL TEXT  

Estrogen-Only Therapy After Hysterectomy and Breast Cancer Risk
JWatch Women's Health 2006;2006:1-1.
FULL TEXT  

Hormone Therapy and Breast Cancer Risk
JWatch Gastroenterology 2006;2006:12-12.
FULL TEXT  

Papers of Note
Sci Aging Knowl Environ 2006;2006:nw8-nw8.
FULL TEXT  

HT and Breast Cancer Risk
JWatch General 2006;2006:2-2.
FULL TEXT