[Estrogen intracrinology: therapy and chemoprevention of breast cancer]

Abstract

Breast cancer affects approximately 1 in 10 women and is the leading cause of death in females between the ages of 40 and 50 years in the Western world. The World Health Organization (WHO) classified estrogens as carcinogenic in humans and one of the most important risk factors of breast cancer. One of the main arguments has been that estrogens can not only promote cancers but may also initiate mutations caused by certain estrogen metabolites. Therapeutics and chemopreventive agents (e.g. tamoxifen) currently in use for breast cancer generally act through an estrogen receptor (ER) mechanism and are thus inappropriate for estrogen-independent disease. In the last decade, numerous studies have searched for new therapeutic and preventive agents acting independently of ER status, hence suitable for cases of estrogen-independent breast cancer. In postmenopausal women, when gonads stop producing estrogens, active hormones are produced locally. These locally produced bioactive estrogens exert their actions in the cells of tissues that have not been considered classical hormone-producing sites (i.e. breast cancer tissue) and where synthesis occurs without release into the circulation. This mechanism has been termed "intracrinology", a phenomenon different from the classical concept of endocrinology. Interference in the local production of estrogens seems to be a good alternative to chemotherapy and chemoprevention of breast carcinoma. In this article, crucial enzymes in estrogen's biosynthesis in the breast and their potential use in therapy and chemoprevention are discussed.