Receptor-positive

HSIEH c Y, SANTELL R c, HASLAM s z, HELFERICH w G (1998) Estrogenic effects of genistein on the growth of estrogen receptor-positive human breast cancer (MCF-7) cells in vitro and in vivo. Cancer Res. 58 3883-3838. 

Tibaduiza, E.C. et al., Excentric cleavage products of beta-carotene inhibit estrogen receptor positive and negative breast tumor cell growth in vitro and inhibit activator protein-1-mediated transcriptional activation, J. Nutr., 132, 1368, 2002. 

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. 

Adjuvant endocrine therapy reduces the rates of relapse and death in patients with hormone-receptor-positive early breast cancer tumors. Adjuvant chemotherapy reduces the rates of relapse and death in all patients with early-stage breast cancer. 

Initial therapy of metastatic breast cancer in women with hormone-receptor-positive tumors should consist of hormonal therapy. 

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. 

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. 

Kim MS, Day CJ, Selinger Cl, Magno CL, Stephens SR, Morrison NA. MCP-1-induced human osteoclast-like cells are tartrate-resistant acid phosphatase, NFATcl, and calcitonin receptor-positive but require receptor activator of NFkap-paB ligand for bone resorption. J Biol Chem 2006 281(2) 1274-1285. 

Fig. 11.4. Model for cholinergic signalling in the intestinal mucosa, providing a possible rationale for AChE secretion by parasitic nematodes. ACh released from enteric cholinergic motor neurons stimulates chloride secretion, mucus secretion and Paneth cell exocytosis through muscarinic receptors. Secretory responses may be modulated by mast cell mediators, either directly or via the induction of neural reflex programmes. The role of muscarinic receptor-positive cells in the lamina propria of rats infected with N. brasiliensis is undetermined, as are potential mechanisms of trans-epithelial transport of the enzymes. Adapted from Cooke (1984).

Kuang TO et al. Differential screening and suppression subtractive hybridisation identified genes differentially expressed in an estrogen receptor-positive breast carcinoma cell line. Nucleic Acids Res 1998 26 1116-1123. 

Immunohistochemical studies have shown that 8 receptors are closely associated with descending serotoninergic neurons [49]. 8 receptor-positive fibers were also found apposed to tyrosine hydroxylase-positive neurons in the locus coeru-... 

Novel agonist 5HTia receptor position emission tomography (PET) ligands derived form l,2,4-triazine-3,5-dione 19 have been synthesized and evaluated in vivo <06JMC125 06BMCL2101>. 

As for the GABAa receptor, positive modulators that enhance glycine receptor activity have been identified. These include alcohols, neurosteroids, tropeines and the divalent metal ion Zn2+, which is highly enriched in some types of excitatory neuron [27], Zn2+ release from such neurons may potentiate glycine receptors at neighboring inhibitory synapses and thus facilitate inhibition following strong excitation. 

Dopamine produces dose-dependent hemodynamic effects because of its relative affinity for cq-, /Jr, /J2-, and Dr (vascular dopaminergic) receptors. Positive inotropic effects mediated primarily by / -receptors become more prominent with doses of 2 to 5 mcg/kg/min. At doses between 5 to 10 mcg/kg/min, chronotropic and -mediated vasoconstricting effects become more prominent. Especially at higher doses, dopamine alters several parameters that increase myocardial oxygen demand and potentially decrease myocardial blood flow, worsening ischemia in some patients with coronary artery disease. 

Raloxifene treatment of osteoporosis was associated with a 76% risk reduction for estrogen-receptor positive breast cancer. An additional study showed that this reduced risk continues for up to 8 years. Among women at high risk for breast cancer, raloxifene was as effective as tamoxifen in reducing the risk of invasive breast cancer and had a lower risk of thromboembolic events. 

Endocrine therapy is the treatment of choice for patients who have hormone receptor-positive metastases in soft tissue, bone, pleura, or, if asymptomatic, viscera. Compared with chemotherapy, endocrine therapy has an equal probability of response and a better safety profile. 

Tamoxifen is the antiestrogen of choice in premenopausal women whose tumors are hormone-receptor positive, unless metastases occur within 1 year of adjuvant tamoxifen. Maximal beneficial effects do not occur for at least 2 months. In addition to the side effects described for adjuvant therapy, tumor flare or hypercalcemia occurs in approximately 5% of patients with MBC. 

Boyan BD, Sylvia VL, Frambach T, Lohmann CE1, Died J, Dean DD, Schwartz Z (2003) Estrogen-dependent rapid activation of protein kinase C in estrogen receptor-positive MCF-7 breast cancer cells and estrogen receptor-negative E1CC38 cells is membrane-mediated and inhibited by tamoxifen. Endocrinology 144(5) 1812—1824... 

Fisher B, Costantino J, Redmond C, Poisson R, Bowman D, Couture J, et al. (1989) A randomized clinical trial evaluating tamoxifen in the treatment of patients with node-negative breast cancer who have estrogen-receptor-positive tumors. N Engl J Med 320(8) 479—484... 

Mueck AO, Seeeger H, Wallwiener D (2003) Effect of statins combined with estradiol on proliferation of human receptor-positive and receptor-negative breast cancer cells. Menopause 10(4) 332—336... 

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