Intratumoral estrogen production in breast carcinoma: Significance of aromatase

It is well known that estrogens are closely involved in the growth of human breast carcinoma, and that the great majority of breast carcinomas express estrogen receptor. Recent studies have demonstrated that estrogens are locally produced in breast carcinoma by several enzymes. Among these, aromatase is generally considered the most important enzyme, and aromatase inhibitors are currently used in the treatment of breast carcinoma in postmenopausal women as an estrogen deprivation therapy. Therefore, in this review, we summarize the results of recent studies on aromatase in breast carcinoma, and we discuss its biological and/or clinical significance. Aromatase was expressed in various cell types in breast carcinoma, such as carcinoma cells, intratumoral stromal cells and adipocytes adjacent to the carcinoma, and the aromatase expression was regulated by various factors, including carcinoma cell-stromal cell interactions, cytokines and nuclear receptors, depending on the cell types. Aromatase was involved not only in local estrogen production but also the inhibition of intratumoral androgen synthesis in breast carcinoma. Finally, tissue concentrations of sex steroids were significantly higher in noninvasive breast carcinoma, regarded as a precursor lesion to invasive carcinoma, than in non-neoplastic breast tissue, and various sex steroid-producing enzymes (including aromatase) were abundantly expressed in noninvasive breast carcinoma tissue. Therefore, sex steroids are locally produced in noninvasive breast carcinoma as well as invasive carcinoma, and endocrine therapies may be clinically effective in a select group of noninvasive breast carcinoma patients.