article/editorial/press: paywalled: Estrogen Plus Progestin and Breast Cancer Incidence and Mortality in the Women’s Health Initiative Observational Study

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Estrogen Plus Progestin and Breast Cancer Incidence and Mortality in the Women’s Health Initiative Observational Study

1. Rowan T. Chlebowski,
2. JoAnn E. Manson,
3. Garnet L. Anderson,
4. Jane A. Cauley,
5. Aaron K. Aragaki,
6. Marcia L. Stefanick,
7. Dorothy S. Lane,
8. Karen C. Johnson,
9. Jean Wactawski-Wende,
10. Chu Chen,
11. Lihong Qi,
12. Shagufta Yasmeen,
13. Polly A. Newcomb and
14. Ross L. Prentice

+ Author Affiliations

1. Affiliation of authors: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA (RTC); Brigham and Women’s Hospital, Harvard Medical School, Boston, MA (JEM); Fred Hutchinson Cancer Research Center, Seattle, WA (GLA, CC, AKA, PAN); University of Pittsburgh, Pittsburgh, PA (JAC); Stanford University, Stanford, CA (MLS); State University of New York, Stony Brook, NY (DSL); University of Tennessee Health Science Center, Memphis, TN (KCJ); University at Buffalo, Buffalo, NY (JWW); University of California at Davis, Sacramento, CA (LQ, SY).

1. 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.

• © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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