This Article  • 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  • Citing articles on Web of Science (18)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Oncology  • Breast Cancer  • Radiologic Imaging  • Women's Health  • Women's Health, Other  • Diagnosis  • Mammography  • Drug Therapy  • Adverse Effects  • Alert me on articles by topic  Social Bookmarking   What's this?

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

Arch Intern Med. 2008;168(4):370-377.

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.

Trial Registration  clinicaltrials.gov Identifier: NCT00000611

Author Affiliations: Los Angeles Biomedical Research Institute at Harbor–UCLA Medical Center, Torrance, California (Dr Chlebowski); Fred Hutchinson Cancer Research Center, Seattle, Washington (Drs Anderson, Chen, and McTiernan and Ms Pettinger); Department of Preventive Medicine, The State University of New York, Stony Brook (Dr Lane); Department of Family and Preventive Medicine, University of San Diego, La Jolla, California (Dr Langer); Department of Medicine, Medical College of Wisconsin, Milwaukee (Dr Gillian); and Center for Reproductive Medicine, Brigham and Women's Hospital, Boston, Massachusetts (Dr Walsh).
Group Information: A full list of the Women's Health Initiative Investigators can be found at http://www.whi.org.

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

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Hormone replacement therapy and breast disease
Marsden
The Obstetrician and Gynaecologist 2010;12:155-163.
ABSTRACT | FULL TEXT  

Estrogen Alone in Postmenopausal Women and Breast Cancer Detection by Means of Mammography and Breast Biopsy
Chlebowski et al.
JCO 2010;28:2690-2697.
ABSTRACT | FULL TEXT  

New-Onset Breast Tenderness After Initiation of Estrogen Plus Progestin Therapy and Breast Cancer Risk
Crandall et al.
Arch Intern Med 2009;169:1684-1691.
ABSTRACT | FULL TEXT  

Cancer Prevention: From 1727 to Milestones of the Past 100 Years
Lippman and Hawk
Cancer Res. 2009;69:5269-5284.
ABSTRACT | FULL TEXT  

Approach to the Patient with Menopausal Symptoms
Martin and Manson
J. Clin. Endocrinol. Metab. 2008;93:4567-4575.
ABSTRACT | FULL TEXT  

Estrogen plus Progestin and Risk of Benign Proliferative Breast Disease
Rohan et al.
Cancer Epidemiol. Biomarkers Prev. 2008;17:2337-2343.
ABSTRACT | FULL TEXT  

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

Estrogen plus Progestin: Diagnostic Mammograms and Biopsies
JWatch Women's Health 2008;2008:3-3.
FULL TEXT