Selective spatial up-regulation of intratumoral stromal aromatase in breast cancer patients: Evidence for imbalance of local estrogen metabolism

Abstract

10105 Background: The suppression of local estrogens levels is of key importance in the treatment of ER positive breast cancer. Essentially all endocrine strategies act by either suppressing estrogen formation or by competitively inhibiting receptor binding in tumor cells. Nevertheless, little is still known about the local expression of aromatase and sultotransferase which are key modulators of intra-tumoral estrogen levels. Methods: We have performed immunohistochemostry to investigate the expression of aromatase and sulfotransferase in 42 samples obtained directly from malignant breast tumors, and compared it to biopsies obtained from uninvolved tissue in the vicinity of the invasion front, and to distant breast tissue. Results: We found that aromatase was equally detectable in both tumor epithelial and stroma, but was mostly epithelial in non-malignant tissues (p=0.00008, Fisher’s Exact Test). Also, aromatase protein expression was significantly more common in tumoral stroma when compared to peri-tumoral and distant breast stroma (p=0.00005, and p<0.00001, respectively). With the notable exception of cystosarcoma phylloides, sulfotransferase protein was only detectable in epithelial tissues, regardless of the location within the diseased breast. Epithelial sulfotransferase was, however, correlated with epithelial aromatase (r=0.35461, p=0.0009, Spearman’s Rho test) and with the epithelial ER status (r=0.29313, p=0.005). Conclusions: Taken together, we have demonstrated a differential aromatase and sulfotransferase protein expression pattern that is dependent of the spacial relation to a malignant breast tumor. Our results indicate a net increase in intra-tumoral active estrogen levels through increased stromal aromatization, while physiological local inactivation by sulfotransferase activity remains essentially unchanged. No significant financial relationships to disclose.