Citation: JAMA Oncology. 1(3):296-305, 2015 Jun..Journal: JAMA oncology.Full author list: Chlebowski RT; Rohan TE; Manson JE; Aragaki AK; Kaunitz A; Stefanick ML; Simon MS; Johnson KC; Wactawski-Wende J; O'Sullivan MJ; Adams-Campbell LL; Nassir R; Lessin LS; Prentice RL.UI/PMID: 26181174.Subject(s): Aged | *Breast Neoplasms/ci [Chemically Induced] | Breast Neoplasms/di [Diagnosis] | Breast Neoplasms/ep [Epidemiology] | Drug Combinations | *Estrogen Replacement Therapy/ae [Adverse Effects] | *Estrogens, Conjugated (USP)/ae [Adverse Effects] | Female | Humans | Incidence | Linear Models | *Medroxyprogesterone Acetate/ae [Adverse Effects] | Middle Aged | Postmenopause | Proportional Hazards Models | Risk Assessment | Risk Factors | Time Factors | Treatment Outcome | United States/ep [Epidemiology]Institution(s): Washington Cancer InstituteActivity type: Journal Article.Medline article type(s): Journal Article | Multicenter Study | Randomized Controlled Trial | Research Support, N.I.H., ExtramuralOnline resources: Click here to access onlineAbbreviated citation: JAMA Oncol. 1(3):296-305, 2015 Jun.Abstract: IMPORTANCE: 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.Abstract: 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.Abstract: DESIGN, SETTING, AND PARTICIPANTS: 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.Abstract: INTERVENTIONS: 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.Abstract: MAIN OUTCOMES AND MEASURES: Time-specific invasive breast cancer incidence rates and exploratory analyses of breast cancer characteristics by intervention and postintervention phases in the 2 HT trials.Abstract: 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.Abstract: CONCLUSIONS AND RELEVANCE: 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.