title: Breast Cancer After Use of Estrogen Plus Progestin and Estrogen Alone: Analyses of Data From 2 Women's Health Initiative Randomized Clinical Trials.
abstract: OBJECTIVE
  The use of menopausal hormone therapy (HT) continues in clinical practice, but reports are conflicting concerning the longer-term breast cancer effects of relatively short-term use.
  
  
  OBJECTIVE
  To report the longer-term influence of menopausal HT on breast cancer incidence in the 2 Women's Health Initiative (WHI) randomized clinical trials.
  
  
  METHODS
  A total of 27,347 postmenopausal women aged 50 to 79 years were enrolled at 40 US centers from 1993 to 1998 and followed up for a median of 13 years through September 2010.
  
  
  METHODS
  A total of 16,608 women with a uterus were randomized to conjugated equine estrogens (0.625 mg/d [estrogen]) plus medroxyprogesterone acetate (2.5 mg/d [progestin]) (E + P) or placebo with a median intervention duration of 5.6 years, and 10,739 women with prior hysterectomy were randomized to conjugated equine estrogens alone (0.625 mg/d) or placebo with a median intervention duration of 7.2 years.
  
  
  METHODS
  Time-specific invasive breast cancer incidence rates and exploratory analyses of breast cancer characteristics by intervention and postintervention phases in the 2 HT trials.
  
  
  RESULTS
  In the E + P trial, hazard ratios (HRs) for the influence of combined HT on breast cancer were lower than 1 for 2 years (HR, 0.71; 95% CI, 0.47-1.08) and steadily increased throughout intervention, becoming significantly increased for the entire intervention phase (HR, 1.24; 95% CI, 1.01-1.53). In the early postintervention phase (within 2.75 years from intervention), there was a sharp decrease in breast cancer incidence in the combined HT group, though the HR remained higher than 1 (HR, 1.23; 95% CI, 0.90-1.70). During the late postintervention phase (requiring patient re-consent), the HR for breast cancer risk remained higher than 1 through 5.5 years (median) of additional follow-up (HR, 1.37; 95% CI, 1.06-1.77). In the estrogen alone trial, the HR for invasive breast cancer risk was lower than 1 throughout the intervention phase (HR, 0.79; 95% CI, 0.61-1.02) and remained lower than 1 in the early postintervention phase (HR, 0.55; 95% CI, 0.34-0.89), but risk reduction was not observed during the late postintervention follow-up (HR, 1.17; 95% CI, 0.73-1.87). Characteristics of breast cancers diagnosed during early and late postintervention phases differed in both trials.
  
  
  CONCLUSIONS
  In the E + P trial, the higher breast cancer risk seen during intervention was followed by a substantial drop in risk in the early postintervention phase, but a higher breast cancer risk remained during the late postintervention follow-up. In the estrogen alone trial, the lower breast cancer risk seen during intervention was sustained in the early postintervention phase but was not evident during the late postintervention follow-up.
authors.affiliation: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California.
authors.forename: Rowan T
authors.initials: RT
authors.lastname: Chlebowski
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Rohan
authors.affiliation: Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: JoAnn E
authors.initials: JE
authors.lastname: Manson
authors.affiliation: Fred Hutchinson Cancer Research Center, Public Health Sciences, Seattle, Washington.
authors.forename: Aaron K
authors.initials: AK
authors.lastname: Aragaki
authors.affiliation: Department of Obstetrics and Gynecology, University of Florida College of Medicine-Jacksonville, Jacksonville.
authors.forename: Andrew
authors.initials: A
authors.lastname: Kaunitz
authors.affiliation: Stanford Prevention Research Center, School of Medicine, Stanford University, Palo Alto, California.
authors.forename: Marcia L
authors.initials: ML
authors.lastname: Stefanick
authors.affiliation: Karmanos Cancer Institute, Department of Oncology, Wayne State University, Detroit, Michigan.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Simon
authors.affiliation: Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis.
authors.forename: Karen C
authors.initials: KC
authors.lastname: Johnson
authors.affiliation: Department of Social and Preventive Medicine, State University of New York at Buffalo.
authors.forename: Jean
authors.initials: J
authors.lastname: Wactawski-Wende
authors.affiliation: Obstetrics/Gynecology, University of Miami Health System Miami, Florida.
authors.forename: Mary J
authors.initials: MJ
authors.lastname: O'Sullivan
authors.affiliation: Georgetown Lombardi Comprehensive Cancer Center, Washington, DC.
authors.forename: Lucile L
authors.initials: LL
authors.lastname: Adams-Campbell
authors.affiliation: Department of Biochemistry and Molecular Medicine, University of California, Davis.
authors.forename: Rami
authors.initials: R
authors.lastname: Nassir
authors.affiliation: Hematology and Medical Oncology, MedStar Washington Hospital Center, Washington, DC.
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Lessin
authors.affiliation: Fred Hutchinson Cancer Research Center, Public Health Sciences, Seattle, Washington.
authors.forename: Ross L
authors.initials: RL
authors.lastname: Prentice
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology; D004338:Drug Combinations; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D004966:Estrogens, Conjugated (USP) / Q000009:adverse effects*; D005260:Female; D006801:Humans; D015994:Incidence; D016014:Linear Models; D017258:Medroxyprogesterone Acetate / Q000009:adverse effects*; D008875:Middle Aged; D017698:Postmenopause; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D004338:Drug Combinations; D004966:Estrogens, Conjugated (USP); C466383:Prempro; D017258:Medroxyprogesterone Acetate