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Breast cancer is often hormone responsive with growth or regression of tumors modulated by endocrine manipulations. Estrogens are known to control the growth of many mammary carcinomas in experimental animals, and humans. Knowledge of tumor response to hormones will greatly improve the ability to plan therapy for breast cancer patients. Chemoprevention of breast cancer has been mostly aimed at reducing the rate of cell division through administration of anti-hormones. Tamoxifen has shown to be species, tissue, and cell-type specific. Cell proliferation in mammary gland occurs in a non-random fashion since there are specific compartments with varied rates of proliferation represented by the terminal end buds that are ready for differentiation into alveolar buds. The aim of this work was to study the effect of 17ß estradiol as well as an antiestrogen, tamoxifen in several in vitro systems to analyze the proliferative capabilities of different kind of cells under controlled experimental conditions. Normal, benign lesions, and duct carcinomas of human breast tissues were processed for organ culture. In the case of the normal breast tissue it was enzymatically digested and culture as organoid culture as well. Several immortalized normal and malignant human breast cell lines were also used in these studies to analyze the effect of 17ß estradiol, progesterone, tamoxifen and anti-progestin RU486. Both 17ß estradiol and progesterone stimulated cell proliferation whereas tamoxifen and RU486 inhibited such effect under these experimental conditions. Thus, in vitro systems allowed to analyze the proliferative capabilities of different kind of cells under controlled experimental conditions. Introduction Sporadic breast cancer, the most common cancer diagnosed in most Western world countries is gradually increasing in incidence. Epidemiological and clinical evidence has identified a number of risk factors for breast cancer, such as family history, age, radiation, diet and history of proliferative breast disease (1-4). When the age-specific curve was examined for breast cancer, it was found that the initial cases occur in early adulthood, and the incidence rate increases sharply with age until menopause, when it slows dramatically. It is a classical model of hormone-dependent malignancy. Such evidence indicate that breast cancer risk is associated with prolonged ovarian function that results in elevated circulating levels of steroid hormones. Principal among these is 17ß estradiol, which is associated with important risk factors, early onset of menarche and late menopause, hormone replacement therapy and postmenopausal obesity as well as with history of proliferative breast disease inducing greater cancer incidence (1). Breast cancer does not develop in the absence of ovaries and ovariectomy causes regression of established malignancies in experimental animal models. Thus, it has been reported that estrogens can induce mammary cancer (5). 17ß estradiol induced in rodents a low incidence of mammary tumors after a long latency period, and only in presence of an intact pituitary axis, with induction of pituitary hyperplasic or adenomas and hyperprolactinemia. 17ß estradiol is considered the primary mitogen for breast tissue (6). Prevention would be the most efficient way of eradicating this disease. Chemoprevention of breast cancer has been mostly aimed at reducing the rate of cell division through administration of anti-hormones (7). A clinical trial demonstrated that the antiestrogen tamoxifen reduces the incidence of breast cancer in women at high risk of developing the disease (8). The non-steroidal antiestrogen tamoxifen (ICI 46,474, Nolvadex) entered clinical trials in 1971 (9). Tamoxifen has been also used based on the concept of adjuvant therapy that started after the removal of the primary tumor in order to control micrometastases before recurrence and death. Tamoxifen, with a long serum half-life, good efficacy, and lack of reported side effects, was the ideal choice as and adjuvant treatment. The initial studies used tamoxifen for up to 5 years (10), with a later decision taken to extend the treatment indefinitely (11). This overall success of adjuvant tamoxifen therapy was recently evaluated in an INTERNATIONAL JOURNAL OF ONCOLOGY 28: 285-295, 2006 285 Susceptibility of human breast epithelial cells in vitro to hormones and drugs