Stroma modifies relationships between risk factor exposure and age-related epithelial involution in benign breast

Delayed age-related lobular involution has been previously associated with elevated breast cancer risk. However, intraindividual variability in epithelial involution status within a woman is undefined. We developed a novel measure of age-related epithelial involution, density of epithelial nuclei in...

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Bibliographic Details
Published in:Modern pathology 2018-07, Vol.31 (7), p.1085-1096
Main Authors: Chollet-Hinton, Lynn, Puvanesarajah, Samantha, Sandhu, Rupninder, Kirk, Erin L., Midkiff, Bentley R., Ghosh, Karthik, Brandt, Kathleen R., Scott, Christopher G., Gierach, Gretchen L., Sherman, Mark E., Vachon, Celine M., Troester, Melissa A.
Format: Article
Language:English
Subjects:
Adult
Age
Aged
Aging - pathology
Benign
Breast cancer
Breast Neoplasms - pathology
Breast surgery
Cellular Microenvironment - physiology
Extracellular Matrix - pathology
Female
Humans
Image processing
Image Processing, Computer-Assisted
Mammary Glands, Human - pathology
Mammography
Middle Aged
Pregnancy
Risk Factors
Stroma
Surgery
Womens health
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Summary:Delayed age-related lobular involution has been previously associated with elevated breast cancer risk. However, intraindividual variability in epithelial involution status within a woman is undefined. We developed a novel measure of age-related epithelial involution, density of epithelial nuclei in epithelial areas using digital image analysis in combination with stromal characteristics (percentage of section area comprising stroma). Approximately 1800 hematoxylin and eosin stained sections of benign breast tissue were evaluated from 416 participants having breast surgery for cancer or benign conditions. Two to sixteen slides per woman from different regions of the breast were studied. Epithelial involution status varied within a woman and as a function of stromal area. Percentage stromal area varied between samples from the same woman (median difference between highest and lowest stromal area within a woman was 7.5%, but ranged from 0.01 to 86.7%). Restricting to women with at least 10% stromal area (N = 317), epithelial nuclear density decreased with age (−637.1 cells/mm2 per decade of life after age 40, p < 0.0001), increased with mammographic density (457.8 cells/mm2 per increasing BI-RADs density category p = 0.002), and increased non-significantly with recent parity, later age at first pregnancy, and longer and more recent oral contraceptive use. These associations were attenuated in women with mostly fat samples (
ISSN:0893-3952
1530-0285
DOI:10.1038/s41379-018-0033-7