Background: Mammographic breast density (BD) is a strong risk factor for breast cancer, but underlying histopathological correlates are not fully understood. In the human breast the main part of the volume constitutes of stroma. We examined the correlation between BD and Ki67, caspase 3, androgen receptor (AR), syndecan-1 , syndecan –4 and decorin in pre-menopausal non cancerous breast tissue.
Method: Pre-menopausal women (n = 55), planned for a reduction mammoplasty and having a breast sample (needle biopsy) at the same time of preoperative mammography, were included. Protein levels of the proteoglycans syndecan-1, syndecan-4, decorin and the AR, Ki67 and caspase 3, were examined by immunohistochemistry (IHC) and gene expression by real-time RT-PCR. Results were compared with regard to BD class (< 20% vs. > 40%) and mean BD (%), using non-parametric analysis and adjustments.
Results: BD (%) decreased significantly with age (p < 0.0001) and with BMI (p = 0.002) but was similar in the follicular and luteal phases. The AR gene expression increased significantly with increasing BD class and with mean BD% (rs = 0.43; p = 0.048, for both), and was strengthened after adjustment for age. After adjustment for age, caspace 3 was positively associated with mean BD (%), with borderline significance (0.55; 0.053), whereas IHC was negatively associated to BD class (-0.61; 0.026). PCR values for Ki67, syndecan-1 and syndecan-4 were numerically higher in dense breasts (p > 0.05 for all).
Conclusion: In pre-menopausal women, gene expression for AR and caspase 3 increased, whereas protein levels of caspase 3 might decrease, with increasing breast density. This limited study showed no significant associations between Ki67, syndecans, decorin and breast density.