We have examined the relationships between the measured properties of breast tissue and mammographic density and other risk factors for breast cancer, using breast tissue obtained at forensic autopsy and not selected for the presence of abnormalities. Methods: We used randomly selected tissue blocks taken from breast tissue slices obtained by s.c. mastectomy at the time of forensic autopsy to measure histologic features using quantitative microscopy. The proportions of the biopsy occupied by

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... ls (estimated by nuclear area), glandular structures, and collagen were determined. These measurements were examined in relation to the percent density in the faxitron image of the tissue slice from which the biopsy was taken and other risk factors for breast cancer. Results: The percent mammographic density was associated with the proportion of the area of the biopsy occupied by nuclei, both epithelial and nonepithelial, and by collagen and the area of glandular structures. Several other risk factors for breast cancer, notably body weight, parity, and number of births, and menopausal status, that are associated with variations in mammographic density, were also associated with differences in one or more of these tissue features. Conclusion: All risk factors for breast cancer must ultimately exert their influence by an effect on the breast, and these findings suggest that, for some risk factors, this influence includes an effect on the number of cells and the quantity of collagen. (Cancer Epidemiol Biomarkers Prev