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Estrogen Plus Progestin and Breast Cancer Incidence and Mortality in the Women’s Health Initiative Observational Study
- Rowan T. Chlebowski,
- JoAnn E. Manson,
- Garnet L. Anderson,
- Jane A. Cauley,
- Aaron K. Aragaki,
- Marcia L. Stefanick,
- Dorothy S. Lane,
- Karen C. Johnson,
- Jean Wactawski-Wende,
- Chu Chen,
- Lihong Qi,
- Shagufta Yasmeen,
- Polly A. Newcomb and
- Ross L. Prentice
+ Author Affiliations
- Correspondence to: Rowan T. Chlebowski, MD, PhD, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1124W Carson St, Torrance, CA, 90502 (e-mail: rowanchlebowski@gmail.com).
- Received August 27, 2012.
- Revision received January 20, 2013.
- Accepted February 13, 2013.
Abstract
Background In the
Women’s Health Initiative (WHI) randomized trial, estrogen plus
progestin increased both breast cancer incidence and
mortality. In contrast, most observational
studies associate estrogen plus progestin with favorable prognosis
breast cancers.
To address differences, a cohort of WHI
observational study participants with characteristics similar to the WHI
clinical
trial was studied.
Methods We identified
41 449 postmenopausal women with no prior hysterectomy and mammogram
negative within 2 years who were either
not hormone users (n = 25 328) or estrogen and
progestin users (n = 16 121). Multivariable-adjusted Cox proportional
hazard
regression was used to calculate hazard ratios
(HRs) with 95% confidence intervals (CI). All statistical tests were
two-sided.
Results After a mean of 11.3 (SD = 3.1) years, with 2236 breast cancers, incidence was higher in estrogen plus progestin users than
in nonusers (0.60% vs 0.42%, annualized rate, respectively; HR = 1.55, 95% CI = 1.41 to 1.70, P
< .001). Women initiating hormone therapy closer to menopause had
higher breast cancer risk with linear diminishing influence
as time from menopause increased (P
< .001). Survival after breast cancer, measured from diagnosis, was
similar in combined hormone therapy users and nonusers
(HR = 1.03, 95% CI = 0.79 to 1.35). On a
population basis, there were somewhat more deaths from breast cancer,
measured from
cohort entry (HR = 1.32, 95% CI = 0.90 to 1.93, P = .15), and more all-cause deaths after breast cancer (HR = 1.65, 95% CI = 1.29 to 2.12, P < .001) in estrogen plus progestin users than in nonusers.
Conclusions Consistent
with WHI randomized trial findings, estrogen plus progestin use is
associated with increased breast cancer incidence.
Because prognosis after diagnosis on combined
hormone therapy is similar to that of nonusers, increased breast cancer
mortality
can be expected.
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