Conjugated equine estrogens and breast cancer risk in the Women's Health Initiative clinical trial and observational study.
The Women's Health Initiative randomized controlled trial found a trend (p = 0.09) toward a lower breast cancer risk among women assigned to daily 0.625-mg conjugated equine estrogens (CEEs) compared with placebo, in contrast to an observational literature that mostly reports a moderate increase in risk with estrogen-alone preparations. In 1993-2004 at 40 US clinical centers, breast cancer hazard ratio estimates for this CEE regimen were compared between the Women's Health Initiative clinical trial and observational study toward understanding this apparent discrepancy and refining hazard ratio estimates. After control for prior use of postmenopausal hormone therapy and for confounding factors, CEE hazard ratio estimates were higher from the observational study compared with the clinical trial by 43% (p = 0.12). However, after additional control for time from menopause to first use of postmenopausal hormone therapy, the hazard ratios agreed closely between the two cohorts (p = 0.82). For women who begin use soon after menopause, combined analyses of clinical trial and observational study data do not provide clear evidence of either an overall reduction or an increase in breast cancer risk with CEEs, although hazard ratios appeared to be relatively higher among women having certain breast cancer risk factors or a low body mass index.
Prentice
Ross L
RL
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA. rprentic@fhcrc.org
Chlebowski
Rowan T
RT
Stefanick
Marcia L
ML
Manson
Joann E
JE
Langer
Robert D
RD
Pettinger
Mary
M
Hendrix
Susan L
SL
Hubbell
F Allan
FA
Kooperberg
Charles
C
Kuller
Lewis H
LH
Lane
Dorothy S
DS
McTiernan
Anne
A
O'Sullivan
Mary Jo
MJ
Rossouw
Jacques E
JE
Anderson
Garnet L
GL
D000368:Aged; D001943:Breast Neoplasms / Q000139:chemically induced* / Q000453:epidemiology*; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D004967:Estrogens / Q000009:adverse effects*; D004966:Estrogens, Conjugated (USP) / Q000009:adverse effects*; D005260:Female; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D016017:Odds Ratio; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012307:Risk Factors; D011795:Surveys and Questionnaires; D014481:United States / Q000453:epidemiology; D016387:Women's Health
D004967:Estrogens; D004966:Estrogens, Conjugated (USP)