W10 - Biological markers of the effect of HT on risk of breast cancer in the Women's Health Initiative clinical trial
Investigator Names and Contact Information
Introduction/Intent
Several studies(#1-7) have examined the relationship between breast cancer risk and endogenous sex hormones among postmenopausal women not using hormone therapy. Most support an association between breast cancer and estrogens, testosterone, and SHBG as individual markers of risk. There are currently no published studies examining whether hormone therapy effects on breast cancer risk are modified by endogenous hormone levels. Further, it is of interest to know whether the observed effects of E+P and E-alone on breast cancer risk are at least in part mediated through changes in circulating levels.
The primary objectives of this project are:
- To explore the extent to which the effects of HT on breast cancer risk are modified by baseline circulating levels of sex hormones and sex hormone binding globulin (SHBG) [hereafter referred to as sex hormones].
- To determine to what extent the changes in circulating levels of sex hormones explain the difference in breast cancer risk associated with E+P and E-Alone.
To address these broad aims we propose to measure a panel of sex hormone levels at baseline and year 1 in a nested case-control study in both HT trials.
References
- Toniolo PG, Levitz M, Zeleniuch-Jacquotte A, et al. A prospective study of endogenous estrogens and breast cancer in postmenopausal women. J Natl Cancer Inst. 1995; 87: 190-197.
- Dorgan JF, Longcope C, Stephenson HE Jr., et al. Relation of prediagnostic serum estrogen and androgen levels to breast cancer risk. Cancer Epidemiol Biomarkers Prev. 1996; 5: 533-539.
- Cauley JA, Lucas FL, Kuller LH, Stone K, Browner WS, Cummings SR. Elevated Serum Estradiol and Testosterone Concentrations are Associated with a High Risk for Breast Cancer. Ann Intern Med. 1999; 130: 270-277.
- Hankinson SE, Willett WC, Manson JE, et al. Plasma sex steroid hormone levels and risk of breast cancer in postmenopausal women. J Natl Cancer Inst. 1998; 90: 1292-1299.
- Missmer SA, Eliassen H, Barbieri RL, Hankinson SE. Endogenous estrogen, androgen and progesterone concentrations and breast cancer risk among postmenopausal women. JNCI 2004;96:1856-65.
- Zeleniuch-Jacquotte A, Shore RE, Koenig KL, et al. Postmenopausal levels of oestrogen, androgen and SHBG and breast cancer: long-term results of a prospective study. British J of Cancer (2004) 90:153-9.
- The Endogenous Hormones, Breast Cancer Collaborative Group, Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies, J. Natl. Cancer Inst. 94 (2002), pp. 606–616.
Data Dictionaries and Study Documentation
This section displays all study-related data dictionaries and study-related files. The investigators for this study will upload the datasets, data dictionaries, and other study-related files. Study-related files will be made available to the public one year after the completion of the ancillary study, with the exception of the datasets, which will only be available to those with a Data Distribution Agreement. Those will be available to those with permission to download and will appear as a download link next to the data dictionary
Data Dictionaries
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Study Documents
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| NameW10 Match Summary.doc | Description |
Related Papers
Sex hormone levels and risk of breast cancer with estrogen plus progestin
Although high endogenous sex hormone levels and estrogen plus progestin (E+P) therapy are associated with increased breast cancer risk, it is unknown whether pretreatment levels of sex hormones modify E+P effect on breast cancer.We conducted a nested case-control study within the Women's Health Initiative randomized clinical trial of E+P. The trial enrolled 16608 postmenopausal women aged 50 to 79 years with intact uterus and no breast cancer history. During a mean of 5.6 years of follow-up, 348...
Keywords: Endogenous Estradiol; Hormone Therapy; Estrogen-Alone Therapy; Estrogen Plus Progestin Therapy; Breast Cancer
Age, body mass, usage of exogenous estrogen, and lifestyle factors in relation to circulating sex hormone-binding globulin concentrations in postmenopausal women
Circulating concentrations of sex hormone-binding globulin (SHBG) have been associated with cardiovascular diseases, type 2 diabetes, metabolic syndrome, and hormone-dependent cancers; however, correlates of SHBG concentrations are not well understood.We comprehensively investigated correlates of SHBG concentrations among 13 547 women who participated in the Women's Health Initiative and who had SHBG measurements. We estimated study- and ethnicity-specific associations of age, reproductive histo...
Keywords: Plasma Sex Hormone Binding Globulin (Shbg); Dietary Factors
Sex hormone associations with breast cancer risk and the mediation of randomized trial postmenopausal hormone therapy effects
Paradoxically, 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.Serum sex hormone concentrations were measured for 348 breast cancer c...
Keywords: Postmenopausal Hormone Therapy; Mediation Analysis; Circulating Sex Hormones; Estrogen-Alone; Estrogen Plus Progestin; Measurement Error
Related Studies: W10
Circulating SHBG (Sex Hormone-Binding Globulin) and risk of ischemic stroke: Findings from the WHI
Abstract Background and Purpose- Circulating levels of SHBG (sex hormone-binding globulin) have been inversely linked to obesity, diabetes mellitus, and other cardiometabolic disorders. It remains uncertain whether low SHBG is prospectively predictive of stroke risk, particularly in women. We investigated whether SHBG is associated with risk of incident ischemic stroke (IS) among women in the WHI (Women's Health Initiative). Methods- From an observational cohort of 161 808 postmenopausal women e...
Keywords: Ischemic Stroke; Sex Hormone Binding Globulin; Sex Hormones; Prevention; Sex Differences
Sex hormones, sex hormones binding globulin (SHBG), and risk of ischemic stroke in men and women in WHI and TOPMed Stroke
Keywords: Stroke; Sex Hormone Binding Globulin; Mendelian Randomization; Single Nucleotide Polymorphisms; Ischemic Stroke
Relation of dietary carbohydrates intake to circulating sex hormone-binding globulin levels in postmenopausal women
BACKGROUND: Low circulating levels of sex hormone-binding globulin (SHBG) have been shown to be a direct and strong risk factor for type 2 diabetes, cardiovascular diseases, and hormone-dependent cancers, although the relation between various aspects of dietary carbohydrates and SHBG levels remains unexplored in population studies. METHODS: Among postmenopausal women with available SHBG measurements at baseline (n = 11,159) in the Women's Health Initiative, we conducted a comprehensive assessmen...
Keywords: Dietary Carbohydrates; Glycemic Index; Glycemic Load; Sex Hormone Binding Globulin (Shbg); Type 2 Diabetes
