Abstract
The biological mechanisms underlying the relationship between mammographic density and breast cancer risk are unknown. Our objective was to examine the association between mammographic density and circulating factors that are putative breast cancer intermediate endpoints. Biologic data from a year-long aerobic exercise intervention trial conducted in 302 postmenopausal women aged 50–74 years were analyzed. Sex hormones, markers of glucose homeostasis, inflammatory markers, and adipokines were assayed in fasting blood drawn at baseline and after 1 year. Area and volumetric measurements of mammographic dense fibroglandular and nondense fatty tissue were made. Multiple linear regression was used to examine the association between the circulating factors and mammographic measures and partial correlations were estimated. Mammographic nondense volume was positively correlated with concentrations of estradiol (r = 0.28), estrone (r = 0.13), insulin (r = 0.41), glucose (r = 0.15), leptin (r = 0.49), and C-reactive protein (r = 0.22), and negatively correlated with sex hormone binding globulin (r = −0.30) and adiponectin (r = −0.12) but correlations became null after adjustment for overall body adiposity as represented by body mass index and waist circumference. With adjustment for overall adiposity, mammographic dense volume, a measure that represents fibroglandular tissue, was negatively correlated with leptin (r = −0.19) and C-reactive protein (r = −0.19). As expected, circulating factors originating from or correlated with adipose tissue were also correlated with mammographic measures of breast adipose tissue, but not after adjustment for overall body adiposity. Interpreting correlations between adiposity-derived factors and mammographic measures whose validity may be affected by adiposity is problematic. To rectify this problem, future studies with very good measures of the volume of fibroglandular tissue in the breast will be necessary.
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Acknowledgments
This study was financially supported through research grants from the Canadian Breast Cancer Research Alliance (#13576 and #017468) and the Alberta Cancer Foundation (#22170). Dr. Friedenreich was supported by career awards from Canadian Institutes of Health Research and the Alberta Heritage Foundation for Medical Research. Drs. Courneya and Cook were supported by the Canada Research Chairs Program. The research programs of Drs. Friedenreich and Courneya have been supported by a Team Grant from the Sociobehavioural Research Program with funds from the Canadian Cancer Society. Dr. Woolcott was funded by National Cancer Institute of Canada/Canadian Cancer Society Studentship for the period in which the bulk of this work was done. We also sincerely thank the participants in the Alberta Physical Activity and Breast Cancer Prevention Trial. Initial study set-up was done by Kim van der Hoek and Marla Orenstein and study coordination by Rosemary Crosby and Ame-Lia Tamburrini in Calgary. Data verification was done by Sandra Blitz. Mammograms were pulled, digitized and analyzed by Christina Edwards, Jenny Gougeon, and Anoma Gunasekara. Final manuscript set-up was done by Heather Neilson.
Ethical Standards
This study was conducted in accordance with the principles set out in Canada’s Tricouncil Policy Statement–Ethical Conduct for Research Involving Humans. Clinicaltrials.gov identifier: NCT00522262.
Conflict of interest
M.J.Y. is a founder and stockholder in Matakina Technologies, a company that produces software products for measurement of mammographic density. Neither the company nor its products were involved directly in this project. The remaining authors declare that they have no conflict of interest.
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Woolcott, C.G., Courneya, K.S., Boyd, N.F. et al. Association between sex hormones, glucose homeostasis, adipokines, and inflammatory markers and mammographic density among postmenopausal women. Breast Cancer Res Treat 139, 255–265 (2013). https://doi.org/10.1007/s10549-013-2534-x
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DOI: https://doi.org/10.1007/s10549-013-2534-x