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Approved research

Association between serum sex steroid hormones and ductal carcinoma in situ among UK women

Principal Investigator: Dr Thomas Rohan
Approved Research ID: 30247
Approval date: August 1st 2017

Lay summary

Endogenous sex steroid hormone levels, particularly oestrogen, are strongly associated with increased risk of invasive ductal carcinoma, but their role in the development of ductal carcinoma in situ DCIS, which is the earliest form of breast cancer, is unclear. This study, therefore, aims to i) investigate the association of oestrogen, testosterone and SHBG with risk of DCIS among women; ii) assess how these associations are modified by age, menopausal status, and weight. This study aims to improve our understanding of aetiology of early stage ductal carcinoma (DCIS). Such information can be useful in developing approaches for the prevention of breast cancer, and is in keeping with the UK Biobank?s aim to improve prevention of cancer. This study will be conducted by researchers at Albert Einstein College of Medicine, Department of Epidemiology and Population Health. We will use the data on serum oestrogen, testosterone and SHBG measurements for all women within the UK Biobank prospective cohort who developed DCIS and those without any previous history of cancer. We will also extract information on potential confounders such as age, BMI, parity and menopausal status, from the data base. We will analyse the data to investigate the association of sex steroid hormones with DCIS. This study will include all women with oestradiol, testosterone and SHBG measurements but will exclude those with a past history of DCIS or invasive cancer, and also those who report use of hormone replacement therapy at the time of the sex steroid hormone measurements.

Current scope

Endogenous sex steroid hormone levels, particularly oestrogen, are strongly associated with increased risk of invasive ductal carcinoma, but their role in the development of ductal carcinoma in situ DCIS, which is the earliest form of breast cancer, is unclear. This study, therefore, aims to i) investigate the association of oestrogen, testosterone and SHBG with risk of DCIS among women;  ii) assess how these associations are modified by age, menopausal status, and weight. iii) We will examine the associations between selected risk factors including age at menarche, age at first birth, parity, menopausal status, hormone therapy use, breast-feeding, obesity, physical inactivity, smoking and alcohol consumption, and risk of DCIS.

Several lines of research have indicated the potential protective role of calcium and vitamin D in breast cancer development. Experimental evidence has shown that calcium is involved in cell proliferation, differentiation and apoptosis, while vitamin D effects include inhibition of cancer cell proliferation, down-regulation of inflammatory mechanisms, and immune response modulation. Results from observational studies  of the association of circulating levels of calcium and vitamin D with breast cancer risk have been mixed. However, no data are available on their association with DCIS.

The present study will examine: i) the association of circulating levels of calcium and vitamin D  with risk of DCIS, and ii) whether the relationship is modified by several risk factors for DCIS such as age, body mass index, physical activity, and menopausal status among others.

New scope

Metabolic syndrome and risk of ductal carcinoma in situ of the breast

Metabolic syndrome (MS) is a cluster of metabolic abnormalities including abdominal obesity, hypertension, relatively high levels of triglycerides and glucose, and low levels of high density lipoprotein (HDL). Based on the National Cholesterol Education Program's Adult Treatment Panel III criteria commonly used in the clinical setting, MS is defined as the occurrence of at least 3 of these 5 pathophysiological conditions. MS has been associated with an increased risk of invasive breast cancer, particularly among postmenopausal women, as suggested by a meta-analysis that combined data from prospective and case-control studies. It is unknown whether MS is associated with the risk of developing ductal carcinoma in situ (DCIS) of the breast. DCIS is considered a nonobligate precursor of invasive breast cancer incidence and mortality. Here, we propose to examine the association between MS and the risk of DCIS in women participating in the UK Biobank study who were breast cancer-free (invasive and in situ) at baseline, and whether this association varies by menopausal status.