ASPO Abstracts
Associations of CD44, CD24, and ALDH1A1 expression in benign breast biopsies with subsequent breast cancer risk
Category: Early Detection & Risk Prediction
Conference Year: 2023
Abstract Body:
Purpose: The stem cell hypothesis of breast carcinogenesis suggests that breast cancer development might be directly related to the size of the stem cell pool and its mitotic activity. We examined the association between stem cell markers CD44, CD24, and ALDH1A1 in benign breast biopsies and breast cancer risk. Methods: This study included women with biopsy-confirmed benign breast disease from a nested case-control study within the Nurses' Health Study (NHS) and NHSII. The data on breast cancer risk factors were obtained from biennial questionnaires. Immunohistochemistry (IHC) was conducted on tissue microarrays with commercial antibodies (CD44 [DAKO] 1:25; CD24 [Invitrogen] 1:200 and ALDH1A1 [Abcam] 1:300). For each core from normal terminal duct- lobular units, the percent positivity was quantified by the Definiens Tissue Studio. For each core, the extent of each marker's expression was assessed on a continuous scale as % of cells that stain positively (across all intensities) for a specific marker out of the total cell count, separately for epithelium and stroma. All analyses were limited to cores with at ≥50 cells of specific tissue type (epithelium or stroma) from Definiens readings. The associations were examined with logistic regression (with the risk estimates for staining ≥10% vs. <10%), while adjusting for breast cancer risk factors. Results: In our study, IHC readings were available for 94 cases/329 controls for CD44, 96 cases/339 controls for CD24, and 96 cases/330 controls for ALDH1A1. In multivariate analysis, stromal expression of CD44 was inversely associated with breast cancer risk (Odds Ratio [OR] for ≥10 vs. <10%=0.57, 95% CI 0.33, 0.97). Stromal expression of CD24 and ALDH1A1 was not associated with breast cancer risk (OR=0.84, 95% CI 0.48, 1.48 and OR=0.79, 95% CI 0.47, 1.32, respectively). We found no association of epithelial expression of any of the three markers with breast cancer risk (p-trend>0.17 for all). Conclusions: Contrary to our hypothesis, the findings suggest an inverse association between stromal CD44 expression and breast cancer risk. Future studies are warranted to confirm our findings and to elucidate the underlying biological mechanisms.
Keywords: stem cell markers, benign breast disease, breast cancer