title: Estrogen Plus Progestin and Lung Cancer: Follow-up of the Women's Health Initiative Randomized Trial.
abstract: BACKGROUND
  In the Women's Health Initiative (WHI) estrogen plus progestin trial, after 5.6 years' intervention and 8 years' median follow-up, more women died from lung cancer in the hormone therapy group (hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.16-2.52; P = .01). Now after 14 years' median follow-up, we reexamined combined hormone therapy effects on lung cancer mortality.
  
  
  METHODS
  In the WHI placebo-controlled trial, 16,608 postmenopausal women aged 50 to 79 years and with an intact uterus were randomly assigned to once-daily 0.625 mg conjugated equine estrogen plus 2.5 mg medroxyprogesterone acetate (n = 8506) or placebo (n = 8102). Incidence and mortality rates for lung cancer were assessed from multivariant proportional hazard models.
  
  
  RESULTS
  After 14 years' cumulative follow-up, there were 219 lung cancers (0.19% per year) in the estrogen plus progestin group and 184 (0.17%) in the placebo group (HR, 1.12; 95% CI, 0.92-1.37; P = .24). While there were more deaths from lung cancer with combined hormone therapy (153 [0.13%] vs. 132 [0.12%], respectively), the difference was not statistically significant (HR, 1.09; 95% CI, 0.87-1.38; P = .45). The statistically significant increase in deaths from lung cancer observed during intervention in women assigned to estrogen plus progestin was attenuated after discontinuation of study pills (linear trend over time, P = .042).
  
  
  CONCLUSIONS
  The increased risk of death from lung cancer observed during estrogen plus progestin use was attenuated after discontinuation of combined hormone therapy.
authors.affiliation: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA. Electronic address: rowanchlebowski@gmail.com.
authors.forename: Rowan T
authors.initials: RT
authors.lastname: Chlebowski
authors.affiliation: Stanford School of Medicine, Stanford, CA.
authors.forename: Heather
authors.initials: H
authors.lastname: Wakelee
authors.affiliation: Fred Hutchinson Cancer Research Center, Public Health Sciences, Seattle, WA.
authors.forename: Mary
authors.initials: M
authors.lastname: Pettinger
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rohan
authors.affiliation: Fred Hutchinson Cancer Research Center, Public Health Sciences, Seattle, WA.
authors.forename: Jingmin
authors.initials: J
authors.lastname: Liu
authors.affiliation: Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI.
authors.forename: Michael
authors.initials: M
authors.lastname: Simon
authors.affiliation: The University of Pittsburgh, Pittsburgh, PA.
authors.forename: Hilary
authors.initials: H
authors.lastname: Tindle
authors.affiliation: Stanford School of Medicine, Stanford, CA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Messina
authors.affiliation: The University of Tennessee Health Science Center, Memphis, TN.
authors.forename: Karen
authors.initials: K
authors.lastname: Johnson
authors.affiliation: The University of California San Francisco, San Francisco, CA.
authors.forename: Ann
authors.initials: A
authors.lastname: Schwartz
authors.affiliation: The North American Menopause Society, Maryland Heights, OH.
authors.forename: Margery
authors.initials: M
authors.lastname: Gass
authors.affiliation: University of Buffalo, School of Public Health and Health Professions, Buffalo, NY.
authors.forename: Jean
authors.initials: J
authors.lastname: Wactawski-Wende
mesh_terms: D000368:Aged; D004359:Drug Therapy, Combination; D004967:Estrogens / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008875:Middle Aged; D011372:Progestins / Q000627:therapeutic use*; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors; D015996:Survival Rate; D016387:Women's Health
chemical_list: D004967:Estrogens; D011372:Progestins
keywords: Estrogen plus progestin; Lung cancer; Lung cancer mortality; Randomized trial; Women's Health Initiative