This Article  • References  • Full text PDF  • Correction  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Contact me when this article is cited  Related Content  • Similar articles in JAMA  Social Bookmarking   What's this?

Karen K. Steinberg, PhD, MSc; Stephen B. Thacker, MD, MSc; S. Jay Smith, MS, MIS; Donna F. Stroup, PhD, MSc; Matthew M. Zack, MD; W. Dana Flanders, MD, DSc; Ruth L. Berkelman, MD

JAMA. 1991;265(15):1985-1990.

Abstract
To quantify the effect of estrogen replacement therapy on breast cancer risk, we combined dose-response slopes of the relative risk of breast cancer against the duration of estrogen use across 16 studies. Using this summary dose-response slope, we calculated the proportional increase in risk of breast cancer for each year of estrogen use. For women who experienced any type of menopause, risk did not appear to increase until after at least 5 years of estrogen use. After 15 years of estrogen use, we found a 30% increase in the risk of breast cancer (relative risk, 1.3; 95% confidence interval [CI], 1.2 to 1.6). The increase in risk was largely due to results of studies that included premenopausal women or women using estradiol (with or without progestin), studies for which the estimated relative risk was 2.2 (CI, 1.4 to 3.4) after 15 years. Among women with a family history of breast cancer, those who had ever used estrogen replacement had a significantly higher risk (3.4; CI, 2.0 to 6.0) than those who had not (1.5; CI, 1.2 to 1.7).

(JAMA. 1991;265:1985-1990)

Author Affiliations
From the Center for Environmental Health and Injury Control (Dr Steinberg and Mr Smith), Epidemiology Program Office (Drs Thacker and Stroup), Center for Chronic Disease Prevention and Health Promotion (Dr Zack), and Center for Infectious Disease (Dr Berkelman), Centers for Disease Control, Atlanta, Ga; and School of Public Health, Emory University, Atlanta, Ga (Dr Flanders).

Footnotes
Use of trade names is for identification only and does not constitute endorsement by the Public Health Service or the US Department of Health and Human Services.

Reprint requests to Center for Environmental Health and Injury Control, Centers for Disease Control, MS F-18,1600 Clifton Rd, Atlanta, GA 30333 (Dr Steinberg).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Mammographic Screening and Risk Factors for Breast Cancer
Cook et al.
Am J Epidemiol 2009;170:1422-1432.
ABSTRACT | FULL TEXT  

Invited Commentary: Postmenopausal Unopposed Estrogen and Breast Cancer Risk in the Women's Health Initiative--Before and Beyond
Linet
Am J Epidemiol 2008;167:1416-1420.
ABSTRACT | FULL TEXT  

Commentary: Hormone therapy and breast cancer incidence: did epidemiologists miss an effect on national trends?
Paul
Int J Epidemiol 2008;37:638-640.
FULL TEXT  

Activation of Estrogen Receptor-{alpha} by the Anion Nitrite
Veselik et al.
Cancer Res. 2008;68:3950-3958.
ABSTRACT | FULL TEXT  

Menopause hormone replacement therapy and cancer risk: an Italian record linkage investigation
Corrao et al.
Ann Oncol 2008;19:150-155.
ABSTRACT | FULL TEXT  

Menopausal hormone therapy and risk of ovarian cancer: systematic review and meta-analysis
Greiser et al.
Hum Reprod Update 2007;13:453-463.
ABSTRACT | FULL TEXT  

Genistein, a soy isoflavone, up-regulates expression of antioxidant genes: involvement of estrogen receptors, ERK1/2, and NF{kappa}B
Borras et al.
FASEB J. 2006;20:2136-2138.
ABSTRACT | FULL TEXT  

Effects of Conjugated Equine Estrogens on Breast Cancer and Mammography Screening in Postmenopausal Women With Hysterectomy
Stefanick et al.
JAMA 2006;295:1647-1657.
ABSTRACT | FULL TEXT  

Menopausal hormone therapy and risk of breast cancer: a meta-analysis of epidemiological studies and randomized controlled trials
Greiser et al.
Hum Reprod Update 2005;11:561-573.
ABSTRACT | FULL TEXT  

Hormone Replacement Therapy in Postmenopausal Women: Breast Tissue Perfusion Determined with MR Imaging--Initial Observations
Delille et al.
Radiology 2005;235:36-41.
ABSTRACT | FULL TEXT  

Estrogen, Estrogen Plus Progestin Therapy, and Risk of Breast Cancer
Colditz
Clin. Cancer Res. 2005;11:909s-917s.
ABSTRACT | FULL TEXT  

Ductal Lavage and Risk Assessment of Breast Cancer
Arun
The Oncologist 2004;9:599-605.
ABSTRACT | FULL TEXT  

Etiology of Hormone Receptor-Defined Breast Cancer: A Systematic Review of the Literature
Althuis et al.
Cancer Epidemiol. Biomarkers Prev. 2004;13:1558-1568.
ABSTRACT | FULL TEXT  

Hormone replacement therapy for the primary prevention of chronic diseases: recommendation statement from the Canadian Task Force on Preventive Health Care
Wathen et al.
CMAJ 2004;170:1535-1537.
FULL TEXT  

Effects of Conjugated Equine Estrogen in Postmenopausal Women With Hysterectomy: The Women's Health Initiative Randomized Controlled Trial
The Women's Health Initiative Steering Committee
JAMA 2004;291:1701-1712.
ABSTRACT | FULL TEXT  

Risks and benefits of hormone replacement therapy: The evidence speaks
Humphries and Gill
CMAJ 2003;168:1001-1010.
ABSTRACT | FULL TEXT  

Individual and Combined Effects of Age, Breast Density, and Hormone Replacement Therapy Use on the Accuracy of Screening Mammography
Carney et al.
ANN INTERN MED 2003;138:168-175.
ABSTRACT | FULL TEXT  

Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women: Principal Results From the Women's Health Initiative Randomized Controlled Trial
Writing Group for the Women's Health Initiative In
JAMA 2002;288:321-333.
ABSTRACT | FULL TEXT  

Management of women with a family history of breast cancer in the North West Region of England: training for implementing a vision of the future
McAllister et al.
J. Med. Genet. 2002;39:531-535.
FULL TEXT  

Identifying and Counseling Women at Increased Risk for Breast Cancer
Rhodes
Mayo Clin Proc. 2002;77:355-361.
ABSTRACT  

Predicting the Cumulative Risk of False-Positive Mammograms
Christiansen et al.
JNCI J Natl Cancer Inst 2000;92:1657-1666.
ABSTRACT | FULL TEXT  

Genetic and Hormonal Risk Factors in Breast Cancer
Martin and Weber
JNCI J Natl Cancer Inst 2000;92:1126-1135.
ABSTRACT | FULL TEXT  

Effect of Hormone Replacement Therapy on Breast Cancer Risk: Estrogen Versus Estrogen Plus Progestin
Ross et al.
JNCI J Natl Cancer Inst 2000;92:328-332.
ABSTRACT | FULL TEXT  

The Prevention of Ankle Sprains in Sports: A Systematic Review of the Literature
Thacker et al.
Am J Sports Med 1999;27:753-760.
ABSTRACT | FULL TEXT  

Prescribing Hormone Replacement Therapy for Menopausal Symptoms
McNagny
ANN INTERN MED 1999;131:605-616.
ABSTRACT | FULL TEXT  

Risk of breast cancer associated with hormone replacement therapy
Dopp and Kolesar
J Oncol Pharm Pract 1999;5:109-116.
ABSTRACT  

Individualizing Therapy to Prevent Long-term Consequences of Estrogen Deficiency in Postmenopausal Women
Col et al.
Arch Intern Med 1999;159:1458-1466.
ABSTRACT | FULL TEXT  

Tamoxifen, Raloxifene, and the Prevention of Breast Cancer
Jordan and Morrow
Endocr. Rev. 1999;20:253-278.
ABSTRACT | FULL TEXT  

Postmenopausal Hormone Replacement Therapy: Effect on Diagnosis and Outcome in Early-Stage Invasive Breast Cancer Treated With Conservative Surgery and Radiation
Fowble et al.
JCO 1999;17:1680-1680.
ABSTRACT | FULL TEXT  

Relative Versus Attributable Risk of Breast Cancer from Estrogen Replacement Therapy
Santen and Petroni
J. Clin. Endocrinol. Metab. 1999;84:1875-1881.
FULL TEXT  

The Individualized Approach to Menopause Management
Walsh
J. Clin. Endocrinol. Metab. 1999;84:1900-1904.
FULL TEXT  

LY353381{middle dot}HCl: An Improved Benzothiophene Analog with Bone Efficacy Complementary to Parathyroid Hormone-(1-34)
Sato et al.
Endocrinology 1998;139:4642-4651.
ABSTRACT | FULL TEXT  

LY353381.HCl: A Novel Raloxifene Analog with Improved SERM Potency and Efficacy In Vivo
Sato et al.
J. Pharmacol. Exp. Ther. 1998;287:1-7.
ABSTRACT | FULL TEXT  

Postmenopausal hormone use was associated with decreased total mortality
Mills and Jones
Evid. Based Nurs. 1998;1:22-22.
FULL TEXT  

Risk of Breast Cancer in Carriers of BRCA Gene Mutations
Orlando et al.
NEJM 1997;337:787-789.
FULL TEXT  

The Critical Role of Alcohol Consumption in Determining the Risk of Breast Cancer with Postmenopausal Estrogen Administration
Zumoff
J. Clin. Endocrinol. Metab. 1997;82:1656-1658.
FULL TEXT  

Patient-Specific Decisions About Hormone Replacement Therapy in Postmenopausal Women
Col et al.
JAMA 1997;277:1140-1147.
ABSTRACT  

Recommendations for Follow-up Care of Individuals With an Inherited Predisposition to Cancer: II. BRCA1 and BRCA2
Burke et al.
JAMA 1997;277:997-1003.
ABSTRACT  

Bone Mass and the Risk of Breast Cancer among Postmenopausal Women
Zhang et al.
NEJM 1997;336:611-617.
ABSTRACT | FULL TEXT  

Effects of Alcohol Ingestion on Estrogens in Postmenopausal Women
Ginsburg et al.
JAMA 1996;276:1747-1751.
ABSTRACT  

Controversies in Management: Hormone replacement therapy for all? Universal prescription is desirable
Toozs-Hobson and Cardozo
BMJ 1996;313:350-351.
FULL TEXT  

Alcohol-Related Problems in Older Persons: Determinants, Consequences, and Screening
Fink et al.
Arch Intern Med 1996;156:1150-1156.
ABSTRACT  

Hormone Replacement Therapy and Breast Cancer Risk
Gambrell
Arch Fam Med 1996;5:341-348.
ABSTRACT  

Hormone Replacement Therapy and Breast Cancer
Stanford and Weiss
Arch Fam Med 1996;5:349-350.
ABSTRACT  

Postmenopausal Estrogens and Breast Cancer
Colditz
Reproductive Sciences 1996;3:50-56.
 

Hormone Replacement and Breast Cancer: A Remaining Controversy?
Adami and Persson
JAMA 1995;274:178-179.
ABSTRACT  

Breast Cancer and Estrogen Therapy
Blair
JAMA 1994;272:1004-1004.
ABSTRACT  

Breast Cancer and Estrogen Therapy-Reply
Steinberg and Smith
JAMA 1994;272:1004-1005.
ABSTRACT  

Estrogen Replacement Therapy in Breast Cancer Survivors: A Time for Change
Cobleigh et al.
JAMA 1994;272:540-545.
ABSTRACT  

More on the Women's Health Initiative
Runowicz et al.
NEJM 1994;330:1619-1620.
FULL TEXT  

Hormonal Treatment of Postmenopausal Women
Belchetz
NEJM 1994;330:1062-1071.
FULL TEXT  

Fortnightly Review: Familial breast cancer
Evans et al.
BMJ 1994;308:183-187.
ABSTRACT | FULL TEXT  

Women's Health Initiative
Eaker and Hahn
NEJM 1994;330:70-71.
FULL TEXT  

Coronary Artery Disease in Women: Risk Factors, Evaluation, Treatment, and Prevention
Kuhn and Rackley
Arch Intern Med 1993;153:2626-2636.
ABSTRACT  

Estrogen Therapy and the Risk of Breast Cancer
Meyer
JAMA 1993;270:2685-2686.
ABSTRACT  

Hormonal Contraception
Baird and Glasier
NEJM 1993;328:1543-1549.
FULL TEXT  

The Postmenopausal Estrogen/Breast Cancer Controversy
Grady and Rubin
JAMA 1993;269:990-990.
ABSTRACT  

Hormone Therapy To Prevent Disease and Prolong Life in Postmenopausal Women
Grady et al.
ANN INTERN MED 1992;117:1016-1037.
ABSTRACT  

The Postmenopausal Estrogen/Breast Cancer Controversy
Henrich
JAMA 1992;268:1900-1902.
ABSTRACT  

General Internal Medicine
Stoeckle and Goodson
JAMA 1992;268:358-360.
ABSTRACT  

Estrogen Therapy for Osteoporosis--Even in the Elderly
Ott
ANN INTERN MED 1992;117:85-86.
ABSTRACT  

Results of Bone Densitometry Affect Women's Decisions about Taking Measures To Prevent Fractures
Rubin and Cummings
ANN INTERN MED 1992;116:990-995.
ABSTRACT  

Estrogen Replacement Therapy and Risk of Breast Cancer: Results of Two Meta-analyses
Vasan
Arch Intern Med 1992;152:1090-1090.
ABSTRACT  

Estrogen Replacement Therapy and Risk of Breast Cancer: Results of Two Meta-analyses-Reply
Dupont and Page
Arch Intern Med 1992;152:1090-1093.
ABSTRACT  

ESTROGEN REPLACEMENT AND BREAST CANCER: A META- ANALYSIS
JWatch General 1991;1991:1-1.
FULL TEXT