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

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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.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
Volume105
Issue number8
DOIs
StatePublished - Apr 17 2013

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Women's Health
Progestins
Observational Studies
Estrogens
Breast Neoplasms
Mortality
Incidence
Confidence Intervals
Hormones
Menopause
Hysterectomy
Cause of Death
Therapeutics
Clinical Trials
Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Chlebowski, R. T., Manson, J. E., Anderson, G. L., Cauley, J. A., Aragaki, A. K., Stefanick, M. L., ... Prentice, R. L. (2013). Estrogen plus progestin and breast cancer incidence and mortality in the women's health initiative observational study. Journal of the National Cancer Institute, 105(8), 526-535. https://doi.org/10.1093/jnci/djt043

Estrogen plus progestin and breast cancer incidence and mortality in the women's health initiative observational study. / Chlebowski, Rowan T.; Manson, Joann E.; Anderson, Garnet L.; Cauley, Jane A.; Aragaki, Aaron K.; Stefanick, Marcia L.; Lane, Dorothy S.; Johnson, Karen C.; Wactawski-Wende, Jean; Chen, Chu; Qi, Lihong; Yasmeen, Shagufta; Newcomb, Polly A.; Prentice, Ross L.

In: Journal of the National Cancer Institute, Vol. 105, No. 8, 17.04.2013, p. 526-535.

Research output: Contribution to journalArticle

Chlebowski, RT, Manson, JE, Anderson, GL, Cauley, JA, Aragaki, AK, Stefanick, ML, Lane, DS, Johnson, KC, Wactawski-Wende, J, Chen, C, Qi, L, Yasmeen, S, Newcomb, PA & Prentice, RL 2013, 'Estrogen plus progestin and breast cancer incidence and mortality in the women's health initiative observational study', Journal of the National Cancer Institute, vol. 105, no. 8, pp. 526-535. https://doi.org/10.1093/jnci/djt043
Chlebowski, Rowan T. ; Manson, Joann E. ; Anderson, Garnet L. ; Cauley, Jane A. ; Aragaki, Aaron K. ; Stefanick, Marcia L. ; Lane, Dorothy S. ; Johnson, Karen C. ; Wactawski-Wende, Jean ; Chen, Chu ; Qi, Lihong ; Yasmeen, Shagufta ; Newcomb, Polly A. ; Prentice, Ross L. / Estrogen plus progestin and breast cancer incidence and mortality in the women's health initiative observational study. In: Journal of the National Cancer Institute. 2013 ; Vol. 105, No. 8. pp. 526-535.
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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.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.",
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AU - Chlebowski, Rowan T.

AU - Manson, Joann E.

AU - Anderson, Garnet L.

AU - Cauley, Jane A.

AU - Aragaki, Aaron K.

AU - Stefanick, Marcia L.

AU - Lane, Dorothy S.

AU - Johnson, Karen C.

AU - Wactawski-Wende, Jean

AU - Chen, Chu

AU - Qi, Lihong

AU - Yasmeen, Shagufta

AU - Newcomb, Polly A.

AU - Prentice, Ross L.

PY - 2013/4/17

Y1 - 2013/4/17

N2 - 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.

AB - 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.

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