Trial reportBreast cancer research : BCR2014
Sex hormone associations with breast cancer risk and the mediation of randomized trial postmenopausal hormone therapy effects.
Trial report in Breast cancer research : BCR, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00000611 (Women's Health Initiative), which is not on this map. Cited by 17 papers, 2 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)
Who cites it
17 citing papers in PubMed, 2 syntheses or guidelines pooled it, 42 citations in OpenAlex.
- Comparison of efficacy of acupuncture-related therapy in the treatment of perimenopausal obesity: a network meta-analysis of randomized controlled trials.Frontiers in medicine · 2025Pooled it
- Long-term hormone therapy for perimenopausal and postmenopausal women.The Cochrane database of systematic reviews · 2017Pooled it
- Randomized Trial Evaluation of the Benefits and Risks of Menopausal Hormone Therapy Among Women 50-59 Years of Age.American journal of epidemiology · 2021Trial
- Overweight, Obesity, and Postmenopausal Invasive Breast Cancer Risk: A Secondary Analysis of the Women's Health Initiative Randomized Clinical Trials.JAMA oncology · 2015Trial
- 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
- Covariate measurement error correction methods in mediation analysis with failure time data.Biometrics · 2014Trial
- The application of mendelian randomization in cancer research: a bibliometric analysis.Discover oncology · 2025Article
- Network Pharmacology, Molecular Docking and Molecular Dynamics to Explore the Potential Immunomodulatory Mechanisms of Deer Antler.International journal of molecular sciences · 2023Article
- Cardiovascular characteristics of patients initially diagnosed breast cancer.Journal of cardiothoracic surgery · 2021Article
- LINC00221 silencing prevents the progression of hepatocellular carcinoma through let-7a-5p-targeted inhibition of MMP11.Cancer cell international · 2021Article
- Pre-Menopausal Women With Breast Cancers Having High AR/ER Ratios in the Context of Higher Circulating Testosterone Tend to Have Poorer Outcomes.Frontiers in endocrinology · 2021Article
- Dual-Outcome Intention-to-Treat Analyses in the Women's Health Initiative Randomized Controlled Hormone Therapy Trials.American journal of epidemiology · 2020Article
- Study on the Antibreast Cancer Mechanism and Bioactive Components ofEvidence-based complementary and alternative medicine : eCAM · 2020Article
- Risk Factor Analysis for Breast Cancer in Premenopausal and Postmenopausal Women of Punjab, India.Asian Pacific journal of cancer prevention : APJCP · 2019Article
- Rhamnetin induces apoptosis in human breast cancer cells via the miR-34a/Notch-1 signaling pathway.Oncology letters · 2019Article
- The modulation of estrogen-induced apoptosis as an interpretation of the women's health initiative trials.Expert review of endocrinology & metabolism · 2016Article
- Menopausal hormone therapy and cancer: changing clinical observations of target site specificity.Steroids · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 11 institutions in 1 country.
Funding
Abstract
introductionParadoxically, a breast cancer risk reduction with conjugated equine estrogens (CEE) and a risk elevation with CEE plus medroxyprogesterone acetate (CEE + MPA) were observed in the Women's Health Initiative (WHI) randomized controlled trials. The effects of hormone therapy on serum sex hormone levels, and on the association between baseline sex hormones and disease risk, may help explain these divergent breast cancer findings.
methodsSerum sex hormone concentrations were measured for 348 breast cancer cases in the CEE + MPA trial and for 235 cases in the CEE trial along with corresponding pair-matched controls, nested within the WHI trials of healthy postmenopausal women. Association and mediation analyses, to examine the extent to which sex hormone levels and changes can explain the breast cancer findings, were conducted using logistic regression.
resultsFollowing CEE treatment, breast cancer risk was associated with higher concentrations of baseline serum estrogens, and with lower concentrations of sex hormone binding globulin. However, following CEE + MPA, there was no association of breast cancer risk with baseline sex hormone levels. The sex hormone changes from baseline to year 1 provided an explanation for much of the reduced breast cancer risk with CEE. Specifically, the treatment odds ratio (95% confidence interval) increased from 0.71 (0.43, 1.15) to 0.92 (0.41, 2.09) when the year 1 measures were included in the logistic regression analysis. In comparison, the CEE + MPA odds ratio was essentially unchanged when these year 1 measures were included.
conclusionsBreast cancer risk remains low following CEE use among women having favorable baseline sex hormone profiles, but CEE + MPA evidently produces a breast cancer risk for all women similar to that for women having an unfavorable baseline sex hormone profile. These patterns could reflect breast ductal epithelial cell stimulation by CEE + MPA that is substantially avoided with CEE, in conjunction with relatively more favorable effects of either regimen following a sustained period of estrogen deprivation. These findings may have implications for other hormone therapy formulations and routes of delivery.
trial registrationclinicaltrials.gov identifier: NCT00000611.
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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.