Associations of stem cell markers CD44, CD24 and ALDH1A1 with mammographic breast density in women with benign breast biopsies

Background: We examined associations of CD44, CD24 and ALDH1A1 breast stem cell markers with mammographic breast density (MBD), a well-established breast cancer (BCa) risk factor. Methods: We included 218 cancer-free women with biopsy-confirmed benign breast disease within the Nurses' Health Study (NHS) and NHSII. The data on BCa risk factors were obtained from biennial questionnaires. Immunohistochemistry (IHC) was done on tissue microarrays. For each core, the IHC expression was assessed using a semi-automated platform and expressed as percent of positively stained cells for each marker out of the total cell count. MBD was assessed with computer-assisted techniques. Generalised linear regression was used to examine the associations of each marker with square root-transformed percent density (PD), absolute dense and non-dense areas (NDA), adjusted for BCa risk factors. Results: Stromal CD44 and ALDH1A1 expression was positively associated with PD (>= 10% vs. <10% beta = 0.56, 95% confidence interval [CI] [0.06; 1.07] and beta = 0.81 [0.27; 1.34], respectively) and inversely associated with NDA (beta per 10% increase = -0.17 [-0.34; -0.01] and beta for >= 10% vs. <10% = -1.17 [-2.07; -0.28], respectively). Epithelial CD24 expression was inversely associated with PD (beta per 10% increase = -0.14 [-0.28; -0.01]. Stromal and epithelial CD24 expression was positively associated with NDA (beta per 10% increase = 0.35 [0.2 x 10(-2); 0.70] and beta per 10% increase = 0.34 [0.11; 0.57], respectively). Conclusion: Expression of stem cell markers is associated with MBD.