Trial reportJAMA2003
Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women's Health Initiative Randomized Trial.
Trial report in JAMA, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 4 registered trials, which are not on this map. Cited by 447 papers, 10 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Women's Health Initiative (WHI)
A Biomarker Study of Mifepristone in Early Stage Breast Cancer
Mifepristone Treatment for Breast Cancer Patients Expressing Levels of Progesterone Receptor Isoform A (PRA) Higher Than Those of Isoform B (PRB): Neoadjuvant Therapy.
Characterizing the Neural Substrates of Irritability in Women: an Experimental Neuroendocrine Model
Who cites it
447 citing papers in PubMed, 10 syntheses or guidelines pooled it, 1,852 citations in OpenAlex.
- Geriatric Breast Cancer: Staging, Molecular Surrogates, and Treatment. A Review & Meta-analysis.Aging and disease · 2024Pooled it
- Hormone replacement therapy and mammographic density: a systematic literature review.Breast cancer research and treatment · 2020Pooled it
- The research burden of randomized controlled trial participation: a systematic thematic synthesis of qualitative evidence.BMC medicine · 2020Pooled it
- European guidance for the diagnosis and management of osteoporosis in postmenopausal women.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2019Guideline
- Risk-Reducing Strategies for Ovarian Cancer inThe oncologist · 2017Pooled it
- Long-term hormone therapy for perimenopausal and postmenopausal women.The Cochrane database of systematic reviews · 2017Pooled it
- Progesterone vs. synthetic progestins and the risk of breast cancer: a systematic review and meta-analysis.Systematic reviews · 2016Pooled it
- Breast Cancer and Menopausal Hormone Therapy by Race/Ethnicity and Body Mass Index.Journal of the National Cancer Institute · 2016Pooled it
- Hormone Replacement Therapy and Risk of Breast Cancer in Korean Women: A Quantitative Systematic Review.Journal of preventive medicine and public health = Yebang Uihakhoe chi · 2015Pooled it
- Body mass index and breast cancer risk according to postmenopausal estrogen-progestin use and hormone receptor status.Epidemiologic reviews · 2014Pooled it
- Estrogen Plus Progestin and Colorectal Cancer: Long-Term Findings From the Women's Health Initiative Randomized Clinical Trial.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024Trial
- Effects of Estradiol/Micronized Progesterone vs. Conjugated Equine Estrogens/Medroxyprogesterone Acetate on Breast Cancer Gene Expression in Healthy Postmenopausal Women.International journal of molecular sciences · 2023Trial
- Breast effects of oral, combined 17β-estradiol, and progesterone capsules in menopausal women: a randomized controlled trial.Menopause (New York, N.Y.) · 2020Trial
- Trial
- Intra-articular tranexamic acid as an adjunct to intravenous tranexamic acid for simultaneous bilateral total knee arthroplasty: a randomized double-blind, placebo-controlled trial.BMC musculoskeletal disorders · 2019Trial
- Trial
- Mammographic Density Change With Estrogen and Progestin Therapy and Breast Cancer Risk.Journal of the National Cancer Institute · 2017Trial
- Estrogen alone and health outcomes in black women by African ancestry: a secondary analyses of a randomized controlled trial.Menopause (New York, N.Y.) · 2017Trial
- Continuous Combined Estrogen Plus Progestin and Endometrial Cancer: The Women's Health Initiative Randomized Trial.Journal of the National Cancer Institute · 2016Trial
- Breast Cancer After Use of Estrogen Plus Progestin and Estrogen Alone: Analyses of Data From 2 Women's Health Initiative Randomized Clinical Trials.JAMA oncology · 2015Trial
387 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 12 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
contextThe Women's Health Initiative trial of combined estrogen plus progestin was stopped early when overall health risks, including invasive breast cancer, exceeded benefits. Outstanding issues not previously addressed include characteristics of breast cancers observed among women using hormones and whether diagnosis may be influenced by hormone effects on mammography.
objectiveTo determine the relationship among estrogen plus progestin use, breast cancer characteristics, and mammography recommendations. DESIGN, SETTING, AND
participantsFollowing a comprehensive breast cancer risk assessment, 16 608 postmenopausal women aged 50 to 79 years with an intact uterus were randomly assigned to receive combined conjugated equine estrogens (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) or placebo from 1993 to 1998 at 40 clinical centers. Screening mammography and clinical breast examinations were performed at baseline and yearly thereafter.
main outcome measuresBreast cancer number and characteristics, and frequency of abnormal mammograms by estrogen plus progestin exposure.
resultsIn intent-to-treat analyses, estrogen plus progestin increased total (245 vs 185 cases; hazard ratio [HR], 1.24; weighted P<.001) and invasive (199 vs 150 cases; HR, 1.24; weighted P =.003) breast cancers compared with placebo. The invasive breast cancers diagnosed in the estrogen plus progestin group were similar in histology and grade but were larger (mean [SD], 1.7 cm [1.1] vs 1.5 cm [0.9], respectively; P =.04) and were at more advanced stage (regional/metastatic 25.4% vs 16.0%, respectively; P =.04) compared with those diagnosed in the placebo group. After 1 year, the percentage of women with abnormal mammograms was substantially greater in the estrogen plus progestin group (716 [9.4%] of 7656) compared with placebo group (398 [5.4%] of 7310; P<.001), a pattern which continued for the study duration.
conclusionsRelatively short-term combined estrogen plus progestin use increases incident breast cancers, which are diagnosed at a more advanced stage compared with placebo use, and also substantially increases the percentage of women with abnormal mammograms. These results suggest estrogen plus progestin may stimulate breast cancer growth and hinder breast cancer diagnosis.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.