Intracrinology of sex steroids in ductal carcinoma in situ (DCIS) of human breast: Comparison to invasive ductal carcinoma (IDC) and non-neoplastic breast

Sex steroids, including those through intratumoral production in an intracrine manner, play important roles in the development of invasive ductal carcinoma (IDC) of human breast, but biological and/or clinical significance of intratumoral production and metabolism of sex steroids, have remained largely unknown in the ductal carcinoma in situ (DCIS), an important precursor lesion of IDC. We recently examined tissue concentration of estradiol and 5α-dihydrotestosterone using liquid chromatography/electrospray tandem mass spectrometry in non-neoplastic breast, DCIS, and IDC tissues. Results of our study suggest that intratumoral concentrations of both estradiol and 5α-dihydrotestosterone are increased in DCIS, which is considered due to intratumoral production of these sex steroids. Therefore, both estradiol and 5α-dehydrotestosterone are considered to play important roles in the development of DCIS as well as IDC through an intracrine manner. Intratumoral metabolism and synthesis of estrogens and androgens as a result of the interactions of various enzymes are therefore also considered to play important roles in hormone dependent DCIS. Aromatase, which is one of the estrogen synthesis enzymes, plays an important role in intratumoral production of estrogen but other enzymes also play pivotal roles in intratumoral estrogen and androgen productions in human breast carcinoma. Therefore, in this review, we also focused on the importance of key intracrine enzymes such as 17β-hydroxysteroid dehydrogenases, steroid sulfatase, estrogen sulfotransferase, 5α-reductases in both IDC and DCIS.