Environment and Breast Cancer: Science Review

Evidence From Humans
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Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women
Key, T. J., Appleby, P. N., Reeves, G. K., Roddam, A., Dorgan, J. F., Longcope, C., Stanczyk, F. Z., Stephenson, H. E., Jr., Falk, R. T., Miller, R., Schatzkin, A., Allen, D. S., Fentiman, I. S., Key, T. J., Wang, D. Y., Dowsett, M., Thomas, H. V., Hankinson, S. E., Toniolo, P., Akhmedkhanov, A., Koenig, K., Shore, R. E., Zeleniuch-Jacquotte, A., Berrino, F., Muti, P., Micheli, A., Krogh, V., Sieri, S., Pala, V., Venturelli, E., Secreto, G., Barrett-Connor, E., Laughlin, G. A., Kabuto, M., Akiba, S., Stevens, R. G., Neriishi, K., Land, C. E., Cauley, J. A., Kuller, L. H., Cummings, S. R., Helzlsouer, K. J., Alberg, A. J., Bush, T. L., Comstock, G. W., Gordon, G. B., Miller, S. R., Longcope, C., Endogenous Hormones Breast Cancer Collaborative, Group Journal of the National Cancer Institute. 2003. 95:16, 1218-26.
Topic area
Body size
Study design
Pooled analysis from nested case-control
Funding agency
Other: Cancer Research UK
Study Participants
Menopausal Status
The menopausal status of women included in this study is listed here.
Post menopausal
Number of Controls
Control: 1,669
Country where study was conducted
USA, UK, Japan and Italy
Participant selection: Inclusion and exclusion criteria
Criteria used to select participants in the study.
In: Eight prospective studies of postmenopausal women were eligible for re-analysis if they contained data on endogenous hormones and breast cancer risk using prospectively collected blood samples on postmenopausal women Ex: studies were excluded that did not have data on the height and weight of participants; participants were excluded if there was missing data for any of the following factors: date of diagnosis of case patients, date of birth, date of blood collection, height, and weight; women using hormone replacement therapy or other exogenous sex hormones at the time of blood collection
Comment about participation selection
Strengths: Pooled analysis of data from eight different cohorts worldwide; data and serum samples were collected prospectively; analyzed levels of five different forms of estrogen and roughly 10 different types of hormones total Limitations: Pooled data set is relatively small; anthropometric data self-reported in four of the eight studies; BMI data is limited since it does not allow for variation among women in the proportions of lean mass and fat mass; results do not conclude which form of estradiol is the most important determining risk for breast cancer; and measurements of hormone concentrations are subject to error associated with assay variation and short-term fluctuations in serum levels within individual women
Exposure Investigated
Exposures investigated
Height, weight and BMI
How exposure was measured
Questionnaire, self-administered (4 studies) Questionnaire, in person (4 studies)
Exposure assessment comment
Anthropometric data self-reported (4 studies)
Ethnic groups with separate analysis
If this study provided a separate analysis by ethnic or racial group, the groups are listed here.
Confounders considered
Other breast cancer risk factors, such as family history, age at first birth, and hormone replacement therapy use, that were taken into account in the study.
Adequately controlled, Confounders: study and age at blood collection
Genetic characterization included
If the study analyzed relationships between environmental factors and inherited genetic variations, this field will be marked “Yes.” “No”, if not.
Description of major analysis
Trends in hormones levels by categories of BMI
Results Comments
The results are compatible with the hypothesis that the increase in breast cancer risk with increasing BMI among postmenopausal women is largely the result of the associated increase in estrogens, particularly bioavailable estradiol.
Author address
Cancer Research U.K. Epidemiology Unit, University of Oxford, Gibson Bldg., Radcliffe Infirmary, Oxford OX2 6HE, UK. Tim.Key@cancer.org.uk