Postmenopausal breast cancer

The answer is d. (Hardman, pp 1275-1276J Tamoxifen is an estrogen antagonist used in the treatment of breast cancer. Postmenopausal women with metastases to soft tissue and whose tumors contain an estrogen receptor are more likely to respond to this agent Little benefit is derived from tamoxifen if the tumor does not have estrogen receptors. 

Many studies have evaluated the relationship between exogenous hormones and development of breast cancer. Postmenopausal estrogen replacement therapy has been the subject of several recent meta-analyses, with conflicting results. The recently reported NCI-sponsored Women s Health Initiative study randomized 80,000 women to take postmenopausal estrogen replacement therapy combined with progesterone or a placebo. This study reported an... 

Valenzano Menada M, Costantini S, Moioli M, Bogliolo S, Papadia A, Ferrero S, Dugnani MC. Evaluation of endometrial thickness in hormone receptor positive early stage breast cancer postmenopausal women switching from adjuvant tamoxifen treatment to anastro-zole. Breast 2008 17 631-6. 

Lentaron) gosetelin USP [65807-02-5] C59Hg4NigOi4 1269.43 (63) postmenopausal breast cancer prostatic carcinoma bone pain common... 

In adults, a few areas may require further study. For example, there is a report of soya consumption causing an increased incidence of hyperplastic epithelial cells in the nipple aspirate fluid of pre- and postmenopausal women.This could constitute a risk factor for breast cancer. Also, the use in herbal medicine of particular plants emphasises that these species have the potential to cause physiological changes. Consequently, the increasing public interest in the use of herbal medicines could lead to unintended (adverse) effects, particularly as most... 

In premenopausal women the ovary is the richest source of aromatase and hence estrogen. Aromatase is confined to the granulosa cells and is produced under the influence of gonadotropins (FSH and LH). Despite being a rich source of aromatase, three separate studies have shown that aromatase inhibitors are unable to sufficiently suppress ovarian estrogen production to postmenopausal levels. One explanation for this phenomenon may be a compensatory rise in gonadotrophins which maintains adequate estrogen production, despite the presence of the inhibitor. As such aromatase inhibitors cannot be used in premenopausal breast cancer patients. After menopause, ovarian... 

STAR trial (Study of tamoxifen and raloxifene), which was completed in 2006, demonstrated additional utility of raloxifene in the prevention and treatment of breast cancer. In fact, the absence of associated uterotrophic effects with raloxifene suggests that it may be a safer agent than tamoxifen for use as a chemopreventative in high-risk postmenopausal women [3] therefore, raloxifene has very recently become a new option for breast cancer prevention now available for physicians and their patients. 

Anastrozole is a selective nonsteroidal aromatase inhibitor that lowers estrogen levels. The pharmacokinetics of anastrozole demonstrate good absorption, with hepatic metabolism the primary route of elimination and only 10% excreted unchanged by the kidney. The elimination half-life is approximately 50 hours. Anastrozole is used for the adjuvant treatment of postmenopausal women with hormone-positive breast cancer and in breast cancer patients who have had disease progression following tamoxifen. Side effects include hot flashes, arthralgias, osteoporosis/bone fractures, and thrombophlebitis. 

Exemestane is an irreversible aromatase inactivator that binds to the aromatase enzyme to block the production of estrogen from androgens. Exemestane is absorbed rapidly after oral administration, with a terminal half-life of 24 hours. The drug is eliminated primarily by the liver and feces, with less than 1% of the dose excreted unchanged in the urine. Exemestane is indicated for the treatment of advanced breast cancer in postmenopausal women who have had disease progression following tamoxifen therapy. Side effects include hot flashes, fatigue, osteoporosis/bone fractures, and flulike symptoms. 

Letrozole is another selective aromatase that inhibits the conversion of androgens to estrogen. Maximum plasma concentrations occur 1 hour after oral dosing concomitant food has not been shown to have an effect on the extent of absorption of letrazole. The terminal half-life is approximately 2 days. Letrozole is used in the treatment of postmenopausal women with hormone-receptor-positive or unknown advanced breast cancer. Side effects include bone pain, hot flushes, back pain, nausea, arthralgia, osteoporosis/bone fractures, and dyspnea. 

Toremifene is an estrogen receptor antagonist. The pharmacokinetics of toremifene are best described by a two-compartment model, with an a half-life of 4 hours and an elimination half-life of 5 days. Peak plasma concentrations are achieved approximately 3 hours after an oral dose. Toremifene is metabolized extensively, with metabolites found primarily in the feces. Toremifene is used for the treatment of metastatic breast cancer in postmenopausal women with estrogen-receptor-positive or unknown tumors. Toremifene causes hot flashes, vaginal bleeding, thromboembolism, and visual acuity changes. 

Long-term use of hormone-replacement therapy and concurrent use of progestins appear to contribute to breast cancer risk.7 The use of postmenopausal estrogen-replacement therapy in women with a history of breast cancer generally is considered contraindicated. However, most experts believe that the safety and benefits of low-dose oral contraceptives currently outweigh the potential risks and that changes in the prescribing practice for the use of oral contraceptives are not warranted. Oral contraceptives are known to reduce the risk of ovarian cancer by about 40% and the risk of endometrial cancer by about 60%. 

Experimental and epidemiologic evidence suggests an association between breast cancer and the Western diet (high in calories, fat, and cooked meats). Obesity in postmenopausal... 

In postmenopausal women, recently reported evidence supporting the use of aromatase inhibitors in the adjuvant setting is intriguing and may usurp the role of tamoxifen. Three different approaches to therapy have been undertaken with these new agents (1) direct comparison with tamoxifen for adjuvant hormonal therapy, (2) sequential use after 5 years of adjuvant tamoxifen therapy, and (3) sequential use after 2 to 3 years of adjuvant tamoxifen. Based on results of several studies, it has been concluded that therapy for postmenopausal women with ER-positive breast cancer should include an aromatase inhibitor.27,47 It is still unclear if the aromatase inhibitor should be used instead of tamoxifen or sequentially after receiving tamoxifen for 2 to 5 years.27 Concerns surrounding loss of bone density, changes in blood lipids, and cardiac and vascular disease require further study.27... 

Tamoxifen can be used in both premenopausal and postmenopausal women with metastatic breast cancer who have tumors that are hormone-receptor-positive. The toxicities of tamoxifen are described in the section on adjuvant endocrine therapy. The only additional toxicity that one might expect to find in the setting of metastatic breast cancer (specifically bone metastases) is a tumor flare or hypercalcemia, which occurs in approximately 5% of patients following the initiation of any SERM therapy and is not an indication to discontinue SERM therapy. It is generally accepted that this is a positive indication that the patient will respond to endocrine therapy. 

Toremifene is another commercially available SERM for the treatment of breast cancer. It exhibits similar efficacy and tolerability to tamoxifen in the metastatic setting. Cross-resistance to toremifene has been demonstrated in patients with tamoxifen-refractory disease.51 Therefore, toremifene appears to be an alternative to tamoxifen in postmenopausal patients with positive or unknown hormone-receptor status with metastatic breast cancer. 

Fulvestrant is a new agent approved for the second-line therapy of postmenopausal metastatic breast cancer patients who have tumors that are hormone-receptor-positive. Studies examining the role of fulvestrant in the treatment of metastatic breast cancer have compared this agent with anastrozole. Given anas-trozole s mechanism of action, only postmenopausal women were eligible for these trials. There is no biologic reason why fulvestrant should not produce similar outcomes in premenopausal... 

Winer EP, Hudis C, Burstein HJ, et al. American Society of Clinical Oncology technology assessment on the use of aromatase inhibitors as adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer Status report 2004. J Clin Oncol 2005 23 619-629. 

In 1990, Vatten et al.51 in Norway subsequently reviewed data on breast cancer risk from a cohort of 14,593 women with 152 cases of breast cancer during a follow up of 12 years on subjects who were between 35 and 51 years old at the beginning of the study and between 46 and 63 years at the end. They reported no overall statistically significant correlation between breast cancer and coffee consumption, but when body mass index was taken into account, lean women who consumed >5 cups per day had a lower risk than women who drank two cups or less. In obese women, however, there was a positive correlation between coffee intake and breast cancer. In a 1993 study, though, Folsom and associates52 failed to find an association between caffeine and postmenopausal breast cancer in 34,388 women in the Iowa Women s Health Study, with a median caffeine intake of 212 mg/day in women who developed breast cancer and 201 mg/day for women who did not and in Denmark, Ewertz53 studied... 

Folsom, A. R., McKenzie, D. R., Bisgard, K. M., Kushi, L. H., Sellers, T. A., No association between caffeine intake and postmenopausal breast cancer incidence in the Iowa Women s Health Study, Am J Epidemiol, 138, 380, 1993. 

Shannon J, Cook LS and Stanford JL. 2003. Dietary intake and risk of postmenopausal breast cancer (United States). Cancer Causes Control 14 19-27. 

Commercialized for different indications breast cancer treatment, contraception, ovulation induction, prevention and treatment of postmenopausal osteoporosis. 

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