Associations of Stem Cell Markers with Lobular Involution in Benign Breast Tissue.

Background: Terminal duct lobular unit (TDLU) involution has been linked to decreased breast cancer risk in some studies. Whether the number/activity of breast stem cells (SC) in noncancerous tissue may influence TDLU involution is unknown. We examined the associations of CD44, CD24, and aldehyde dehydrogenase family 1 member A1 (ALDH1A1) SC markers with TDLU involution.

Methods: We included 309 cancer-free women with biopsy-confirmed benign breast disease. IHC was performed using tissue microarrays. For each core, IHC expression was assessed using semiautomated software as the percentage of positively stained cells for each marker. Eight TDLU involution measures were assessed with an established computational pathology algorithm. Generalized linear regression was used to examine the associations of each marker (≥10% vs. <10%) with each TDLU involution measure (log-transformed), adjusted for breast cancer risk factors.

Results: CD44 was positively associated with acini counts per nonadipose tissue area [epithelial: β = 0.307 (95% confidence interval, 0.072-0.542); stromal: β = 0.249 (0.005-0.494)] and median acini density [epithelial: β = 0.127 (0.025-0.229); stromal: β = 0.143 (0.037-0.249)]. Epithelial ALDH1A1 was positively associated with median acini density [β = 0.161 (0.045-0.278)], and stromal ALDH1A1 was positively associated with median acini counts per TDLU [β = 0.145 (0.018-0.273)].

Conclusions: Higher CD44 and ALDH1A1 expressions in epithelial and stromal regions were associated with lower TDLU involution.

Impact: We present the first epidemiologic evidence of the association of SC markers with TDLU involution.