Cancer, aromatase inhibition and breast

Anxiolytic agents, pyrido[l,2-a]benzimida-zoles as, 36 (1999) 169 Aromatase inhibition and breast cancer, 26 (1989) 253 33 (1996) 147 Arthritis neurokinin receptors in, 43 (2005) 53... 

Grube BJ, Eng ET, Yeh CK, Kwon A and Shiuan C. 2001. White button mushroom phytochemicals inhibit aromatase activity and breast cancer cell proliferation. J Nutr 13 3288-3293. 

Camptothecin and its analogues, 34 (1997) 69 Cancer, aromatase inhibition and breast, 26... 

Anastrazole is a nonsteroidal, type H, aromatase inhibitor that is 200 times more potent than aminoglutethimide. It is eliminated primarily via hqDatic metabolism, has a terminal half life of 50 h with steady state concentrations achieved approximately 10 days with once daily dosing regimens. It is administered orally at a dose of 1 mg/day that achieves near maximal aromatase inhibition and hence estrogen suppression in breast cancer patients. No effect on adrenal steroidogenesis has been observed at up to ten times the daily recommended dose. When used in the metastatic setting, anastrozole has been shown... 

Jones SA, Jones SE (2000) Exemestane a novel aromatase inactivator for breast cancer. Clin Breast Cancer 1 211-216 Lee RJ, Armstrong AC, Wardley AM (2012) Le-trozole advancing hormone therapy in breast cancer. Womens Health 8 611 18 Hong Y, Yu B, Sherman M, Yuan YC, Zhou D, Chen S (2007) Molecular basis for the aromatization reaction and exemestane-mediated irreversible inhibition of human aromatase. Mol Endocrinol 21 401 14... 

There is a clear correlation between adiposity and breast cancer, which is almost certainly due to synthesis of oestradiol in adipose tissue enterolactone and some of the other flavonoid phyto-oestrogens inhibit aromatase and will therefore reduce synthesis of oestradiol in adipose tissue. 

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. 

Chlebowski RT, Col N, Winer EP et al. (2002) American Society of Clinical Oncology Technology assessment of pharmacologic interventions for breast cancer risk reduction including tamoxifen, raloxifene, and aromatase inhibition. J Clin Oncol 20(15) 3328—3343... 

Drugs that can be used to control tumour cell proliferation inhibit a variety of enzymes, including thymidylate synthase and topoisomerase (Chapter 20). The enzyme aromatase converts a ring in a steroid to an aromatic ring. It converts, for example, adrenal steroid hormones into female sex hormones, which bind to oestrogenic receptors in the ovary or breast and increase the risk of ovarian or breast cancer. Aromatase inhibitors are used to treat patients with breast or ovarian cancers that are sensitive to oestrogen. Unfortunately, none of the inhibitors is specific for enzymes in tumour cells and they can therefore have severe side-effects (Chapter 21). 

Testolactone is a synthetic drug related to testosterone. It is used for palliative treatment of advanced breast cancer in postmenopausal women and in women who have had their ovaries removed. The principal action of testolactone is reported to be inhibition of steroid aromatase activity and the reduction in estrone synthesis. The most common adverse effects are nausea, vomiting, and anorexia. An advantage is that it does not cause women to develop male characteristics such as a deep voice or facial hair. 

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