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, Ross L. Prentice

Research output: Contribution to journalArticlepeer-review

149 Scopus citations


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.MethodsWe 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.ResultsAfter 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.ConclusionsConsistent 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.

Original languageEnglish (US)
Pages (from-to)526-535
Number of pages10
JournalJournal of the National Cancer Institute
Issue number8
StatePublished - Apr 17 2013

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


Dive into the research topics of 'Estrogen plus progestin and breast cancer incidence and mortality in the women's health initiative observational study'. Together they form a unique fingerprint.

Cite this