Breast cancer hormone-related

A stmcturally related series of phenyfiiydrazones resulted ia the selection of compound A-007 [2675-35-6] (DEKK-TEC)(37) for the treatment of hormone-dependent tumors. A-007 is an antiestrogen that, ia contrast to tamoxifen, demonstrated inhibitory activity both ia the presence and absence of estradiol ia ZR-75-1 estrogen-dependent human breast cancer cells, and afforded more protection than tamoxifen ia the 7,12-dimethylbenz[i7]anthracene... 

Prostate Cancer. Evidence that phytoestrogens can influence the incidence of male-speciflc diseases is restricted to prostate cancer, and is largely of an observational nature. In the UK, prostate cancer is the most common hormone-related cancer in men. However, like breast cancer in women, it is comparatively rare as a clinically evident disease in men living in Asian countries. 

Breast cancer is one of the most common forms of cancer affecting women and, in Western countries, the incidence is rising. The risk of breast cancer increases markedly with age, although a decrease in the rate occurs after the menopause, suggesting that development is hormone-dependent. To date, a number of hormone-related risk factors have been identified (Bingham et al, 1998). Countries such as Japan have relatively low rates of breast cancer, which have been associated with consumption of a diet high in soy foods. Currently, however, the data from epidemiological studies is inconclusive. 

Based on this concept of correlation between high replication rate/high persistent mutation risk, Pike et al. (1983) formulated the hypothesis of breast tissue age and developed a mathematical model to predict the effects of exposure to ovarian hormones. This model incorporates reproductive and endocrine items related to breast cancer and is able to predict the relative risk of individual situations with results that are very close to those observed in clinical trials. According to this hypothesis, both the years of exposure and the circulating serum levels of estrogens are associated to short-term breast cancer risk in postmenopausal women (Toniolo et al. 1995). 

First we shall describe the effects of tamoxifen, a first-generation SERM used as adjuvant treatment in women with breast cancer, on uterine leiomyomas and endometriosis. Considerable space will be devoted to raloxifene, a second-generation SERM administered for the prevention and treatment of postmenopausal women recently tested for the treatment of these two sex-hormone-related diseases. Unfortunately, at present no or very little data are available on the new third-generation SERMs such as lasofoxifene, idroxifene, droloxifene, ospemifene, azomifene, fulvestrant, and MDL 103.323. 

Hormones regulate many important bodily functions and are also associated with cancer. One of the first hints of the relationship of hormones to cancers was the observation that nuns had a greater incidence of breast cancer. This was naturally related to the nuns not having children and now we know that breast cancer may be hormone related. Since then there have been numerous studies on the use of birth control with cancer, childbirth, and most recently hormone replacement association with cancer. In males there is ongoing study of the hormones and prostate cancer. While it is clear that hormones and cancer are related, the exact characterization of this relationship is still unclear. 

Hormone-related cancers of the breast, ovary, endometrium, and prostate have been reported to vary by as much as 5 to 20-fold between populations. Migrant studies indicate that the difference is largely attributable to environmental factors rather than genetics [219,220]. The highest rates of these cancers are typically observed in populations with Western lifestyles that include relatively high fat, meat-based, low fiber diets, whereas the lowest rates are typically observed in Asian populations with Eastern lifestyles that include plant-based diets with a high content of phytoestrogens [219,221]. 

It is clear from the studies reported in Table 1 (133-149) that there is no simple relation between treatment with hormonal oral contraceptives and the incidence of breast cancer. As in the case of other neoplasms, studies are confounded by the influence of many factors, including age, parity, age at first delivery, family history, pre-existent fibrocystic disease, geographical or... 

Stanford JL, Weiss NS, Voigt LF, Dating JR, Habel LA, Rossing MA. Combined estrogen and progestin hormone replacement therapy in relation to risk of breast cancer in middle-aged women. JAMA 1995 274(2) 137-42. 

Fournier A, Berrino F, Riboli E, Avenel V, Clavel-Chapelon F. Breast cancer risk in relation to different types of hormone replacement therapy in the E3N-EPIC cohort. Int J Cancer 2005 114 448-54. 

The complexity of the relation between hormonal replacement therapy and breast cancer has been stressed in previous volumes (SED-14, 1454) (SEDA-22, 465), and much depends on the type of replacement therapy given and the class of tumor studied. This latter point has been underscored by a US study that provided evidence that the use of combined hormonal replacement therapy increases the risk of lobular, but not ductal, breast carcinoma in middle-aged women (28). 

A possible link between breast cancer in women and thyroid hormone therapy was suggested on the basis of a retrospective study of patients with breast cancer (SEDA-3, 340). A subsequent statistical re-analysis of the original data failed, as did later studies, to confirm such a relation (SEDA-3, 340 SEDA-4, 294 57). 

In women reserpine causes a small increase in circulating concentrations of prolactin (1006), which could be related to the small increase in the risk of breast cancer. In 27 hypertensive men reserpine 0.25 mg/day for 3 months had no effect on testosterone, dihydrotestosterone, estradiol, luteinizing hormone, or prolactin (1007). 

Corticosteroids have been useful in the treatment of acute leukemia, lymphoma, multiple myeloma, and other hematologic malignancies as well as in advanced breast cancer. In addition, they are effective as supportive therapy in the management of cancer-related hypercalcemia. The steroid hormones and related agents most useful in cancer therapy are listed in Table 55-5. 

With the identification and characterization of all members of the kallikrein gene family, accumulating evidence indicates that other kallikreins might be also related to hormonal (e.g., breast, prostate, testicular, and ovarian cancers) and other malignancies. KLK6 and KLK10 were originally isolated by differential display from breast cancer libraries [216],... 

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