Effects of conjugated equine estrogens on breast cancer and mammography screening in postmenopausal women with hysterectomy.
BACKGROUND
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.


METHODS
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.


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


METHODS
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.


BACKGROUND
clinicaltrials.gov Identifier: NCT00000611.
Stefanick
Marcia L
ML
Stanford Prevention Research Center, Department of Medicine, Stanford University, Stanford, Calif 94305, USA. stefanick@stanford.edu
Anderson
Garnet L
GL
Margolis
Karen L
KL
Hendrix
Susan L
SL
Rodabough
Rebecca J
RJ
Paskett
Electra D
ED
Lane
Dorothy S
DS
Hubbell
F Allan
FA
Assaf
Annlouise R
AR
Sarto
Gloria E
GE
Schenken
Robert S
RS
Yasmeen
Shagufta
S
Lessin
Lawrence
L
Chlebowski
Rowan T
RT
D000368:Aged; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000453:epidemiology*; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007044:Hysterectomy; D008327:Mammography; D008875:Middle Aged; D017698:Postmenopause; D016016:Proportional Hazards Models; D018570:Risk Assessment
D004966:Estrogens, Conjugated (USP)