Association of Menopausal Hormone Therapy With Breast Cancer Incidence and Mortality During Long-term Follow-up of the Women's Health Initiative Randomized Clinical Trials

被引:270
作者
Chlebowski, Rowan T. [1 ]
Anderson, Garnet L. [2 ]
Aragaki, Aaron K. [2 ]
Manson, JoAnn E. [3 ]
Stefanick, Marcia L. [4 ]
Pan, Kathy [1 ]
Barrington, Wendy [5 ]
Kuller, Lewis H. [6 ]
Simon, Michael S. [7 ]
Lane, Dorothy [8 ]
Johnson, Karen C. [9 ]
Rohan, Thomas E. [10 ]
Gass, Margery L. S. [2 ]
Cauley, Jane A. [6 ]
Paskett, Electra D. [11 ]
Sattari, Maryam [12 ]
Prentice, Ross L. [2 ]
机构
[1] Harbor UCLA Med Ctr, Lundquist Inst Biomed Innovat, 1124 W Carson St,Bldg N-18, Torrance, CA 90502 USA
[2] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA
[3] Harvard Med Sch, Brigham & Womens Hosp, Div Publ Hlth Sci, Boston, MA 02115 USA
[4] Stanford Univ, Sch Med, Stanford Prevent Res Ctr, Stanford, CA 94305 USA
[5] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA
[6] Univ Pittsburgh, Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA
[7] Wayne State Univ, Karmanos Canc Inst, Dept Oncol, Detroit, MI USA
[8] SUNY Stony Brook, Dept Family Populat & Prevent Med, Stony Brook, NY 11794 USA
[9] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN 38163 USA
[10] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA
[11] Ohio State Univ, Coll Publ Hlth, Columbus, OH 43210 USA
[12] Univ Florida Hlth Internal Med, Div Gen Internal Med, Gainesville, FL USA
来源
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION | 2020年 / 324卷 / 04期
基金
美国国家卫生研究院;
关键词
ESTROGEN PLUS PROGESTIN; POSTMENOPAUSAL WOMEN; SYMPTOM EXPERIENCE; EQUINE ESTROGEN; TAMOXIFEN; HYSTERECTOMY; PREVENTION; OUTCOMES; RISK;
D O I
10.1001/jama.2020.9482
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
IMPORTANCE The influence of menopausal hormone therapy on breast cancer remains unsettled with discordant findings from observational studies and randomized clinical trials. OBJECTIVE To assess the association of prior randomized use of estrogen plus progestin or prior randomized use of estrogen alone with breast cancer incidence and mortality in the Women's Health Initiative clinical trials. DESIGN, SETTING, AND PARTICIPANTS Long-term follow-up of 2 placebo-controlled randomized clinical trials that involved 27347 postmenopausal women aged 50 through 79 years with no prior breast cancer and negative baseline screening mammogram. Women were enrolled at 40 US centers from 1993 to 1998 with follow-up through December 31, 2017. INTERVENTIONS In the trial involving 16 608 women with a uterus, 8506 were randomized to receive 0.625 mg/d of conjugated equine estrogen (CEE) plus 2.5 mg/d of medroxyprogesterone acetate (MPA) and 8102, placebo. In the trial involving 10 739 women with prior hysterectomy, 5310 were randomized to receive 0.625 mg/d of CEE alone and 5429, placebo. The CEE-plus-MPA trial was stopped in 2002 after 5.6 years' median intervention duration, and the CEE-only trial was stopped in 2004 after 7.2 years' median intervention duration. MAIN OUTCOMES AND MEASURES The primary outcome was breast cancer incidence (protocol prespecified primary monitoring outcome for harm) and secondary outcomes were deaths from breast cancer and deaths after breast cancer. RESULTS Among 27 347 postmenopausal women who were randomized in both trials (baseline mean [SD] age, 63.4 years [7.2 years]), after more than 20 years of median cumulative follow-up, mortality information was available for more than 98%. CEE alone compared with placebo among 10 739 women with a prior hysterectomy was associated with statistically significantly lower breast cancer incidence with 238 cases (annualized rate, 0.30%) vs 296 cases (annualized rate, 0.37%; hazard ratio [HR], 0.78; 95% CI, 0.65-0.93; P =.005) and was associated with statistically significantly lower breast cancer mortality w th 30 deaths (annualized mortality rate, 0.031%) vs 46 deaths (annualized mortality rate, 0.046%; HR, 0.60; 95% CI, 0.37-0.97; P =.04). In contrast, CEE plus MPA compared with placebo among 16 608 women with a uterus was associated with statistically significantly higher breast cancer incidence with 584 cases (annualized rate, 0.45%) vs 447 cases (annualized rate, 0.36%; HR, 1.28; 95% CI, 1.13-1.45; P <.001) and no significant difference in breast cancer mortality with 71 deaths (annualized mortality rate, 0.045%) vs 53 deaths (annualized mortality rate, 0.035%; HR, 1.35; 95% CI, 0.94-1.95; P=.11). CONCLUSIONS AND RELEVANCE In this long-term follow-up study of 2 randomized trials, prior randomized use of CEE alone, compared with placebo, among women who had a previous hysterectomy, was significantly associated with lower breast cancer incidence and lower breast cancer mortality, whereas prior randomized use of CEE plus MPA, compared with placebo, among women who had an intact uterus, was significantly associated with a higher breast cancer incidence but no significant difference in breast cancer mortality.
引用
收藏
页码:369 / 380
页数:12
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