Cancer
Oral contraceptive use and the expression of CD44, CD24, and ALDH1A1 stem cell markers in benign breast tissue Maisey Ratcliffe* Maisey Ratcliffe Yujing J. Heng Brian Sardella Rulla M. Tamimi Lusine Yaghjyan
Purpose: We investigated, for the first time, the association between oral contraceptive (OC) use and the expression of CD44, CD24, and ALDH1A1 stem cell (SC) markers in benign biopsy tissue.
Methods: This study included 731 cancer-free women with biopsy-confirmed benign breast disease (BBD) within the Nurses’ Health Study II cohort. Information on OC use was collected in 1989 and then updated biennially. Histologically normal breast tissue cores were used to construct tissue microarrays (TMAs). Immunohistochemistry (IHC) was performed on TMA sections to analyze the expression of SC markers. For each core, the IHC expression was assessed using semi-automated software and reported as the % of positively stained cells for each of the markers out of the total cell count. All expression measures were log-transformed for analysis. Generalized linear regression was used to examine the associations of OCs (use status, total duration, age at first and last use, and time since last use) with each marker’s expression (within stroma and epithelium), while adjusting for known breast cancer risk factors and BBD subtype.
Results: In this study of 731 cancer-free women, the average age at the time of biopsy was 44 years (range 27-63), with the majority of participants being premenopausal at the time of biopsy (81%). OC use status at biopsy was positively associated with stromal CD44 expression (current vs. never β=0.75, 95% Confidence Interval [CI] 0.11, 1.39, p-trend=0.02). Age at first use was inversely associated with CD44 expression (in stroma: β= -0.04, 95% CI -0.08, -0.01; in epithelium β=-0.04, 95% CI -0.06, -0.02). No associations were found for CD24 and ALDH1A1. Total duration, age at last use, and time since last use were not associated with the expression of any of the three markers.
Conclusions: Our findings suggest a greater expression of CD44 in stroma of current OC users and a reduced CD44 expression with a later age at first OC use.