TY - JOUR
T1 - Breast cancer after use of estrogen plus progestin and estrogen alone
T2 - Analyses of data from 2 women's health initiative randomized clinical trials
AU - Chlebowski, Rowan T.
AU - Rohan, Thomas E.
AU - Manson, Joann E.
AU - Aragaki, Aaron K.
AU - Kaunitz, Andrew
AU - Stefanick, Marcia L.
AU - Simon, Michael S.
AU - Johnson, Karen C.
AU - Wactawski-Wende, Jean
AU - O'Sullivan, Mary J.
AU - Adams-Campbell, Lucile L.
AU - Nassir, Rami
AU - Lessin, Lawrence S.
AU - Prentice, Ross L.
N1 - Funding Information:
Dr Chlebowski reported being a consultant for AstraZenea, Novartis, Amgen, Genomic Health and Novo Nordisk; receiving funding support from Amgen; and serving on the speaker's bureau for Novartis and Genentech. No other disclosures are reported. The Women's Health Initiative (WHI) program is reported by the National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health, Department of Health and Human Services through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221.
Publisher Copyright:
Copyright 2015 American Medical Association. All rights reserved.
PY - 2015/6/1
Y1 - 2015/6/1
N2 - 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. 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. 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. 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. 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 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.
AB - 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. 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. 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. 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. 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 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.
UR - http://www.scopus.com/inward/record.url?scp=84965092976&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84965092976&partnerID=8YFLogxK
U2 - 10.1001/jamaoncol.2015.0494
DO - 10.1001/jamaoncol.2015.0494
M3 - Article
C2 - 26181174
AN - SCOPUS:84965092976
VL - 1
SP - 296
EP - 305
JO - JAMA oncology
JF - JAMA oncology
SN - 2374-2437
IS - 3
ER -