Breast Cancer After Use of Estrogen Plus Progestin and Estrogen Alone: Analyses of Data From 2 Women's Health Initiative Randomized Clinical Trials.
Breast Cancer After Use of Estrogen Plus Progestin and Estrogen Alone: Analyses of Data From 2 Women's Health Initiative Randomized Clinical Trials.
- 2015
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. 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. 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. 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. 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. 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. 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.
English
*Breast Neoplasms/ci [Chemically Induced]
*Estrogen Replacement Therapy/ae [Adverse Effects]
*Estrogens, Conjugated (USP)/ae [Adverse Effects]
*Medroxyprogesterone Acetate/ae [Adverse Effects]
Aged
Breast Neoplasms/di [Diagnosis]
Breast Neoplasms/ep [Epidemiology]
Drug Combinations
Female
Humans
Incidence
Linear Models
Middle Aged
Postmenopause
Proportional Hazards Models
Risk Assessment
Risk Factors
Time Factors
Treatment Outcome
United States/ep [Epidemiology]
Washington Cancer Institute
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural
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. 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. 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. 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. 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. 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. 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.
English
*Breast Neoplasms/ci [Chemically Induced]
*Estrogen Replacement Therapy/ae [Adverse Effects]
*Estrogens, Conjugated (USP)/ae [Adverse Effects]
*Medroxyprogesterone Acetate/ae [Adverse Effects]
Aged
Breast Neoplasms/di [Diagnosis]
Breast Neoplasms/ep [Epidemiology]
Drug Combinations
Female
Humans
Incidence
Linear Models
Middle Aged
Postmenopause
Proportional Hazards Models
Risk Assessment
Risk Factors
Time Factors
Treatment Outcome
United States/ep [Epidemiology]
Washington Cancer Institute
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural