Hormonal Tamoxifen

Alternatives to steroid hormone therapy for osteoporosis include raloxifene, bisphosphonates, sodium fluoride, vitamin D and calcium supplementation, calcitonin, and parathyroid hormone. Tamoxifen has estrogenic effects on bone and delays bone loss in postmenopausal women. However as a result of estrogenic activity in the uterus, long-term tamoxifen administration has been associated with an increased risk of... 

Figure 40-2. Sites of action of several ovarian hormones and their analogs. Clomiphene, a partial agonist, is mainly an antagonist at pituitary estrogen receptors this prevents negative feedback and increases the output of the pituitary gonadotropic hormones. Tamoxifen, a SERM, is mainly an antagonist at estrogen receptors in the breast but acts as an agonist in bone Contraceptives reduce FSH and LH output from the pituitary by activating feedback receptors.

The 39-year-old client diagnosed with breast cancer is prescribed the antiestrogen hormone tamoxifen (Nolvadex). Which information is most important for the nurse to teach the client ... 

Barbara, unemployed, formerly worked with the developmentally and mentally impaired. Breast cancer, stage 2, diagnosed in 2005 at age fifty. (Treatment mastectomy. Chemo doxorubicin, cyclophosphamide, pacli-taxel. Targeted therapy trastuzumab [Herceptin], Anti-hormonals tamoxifen, then anastrozole.)... 

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... 

In addition to the sex hormones and corticosteroids, other steroid dmgs have substantial worldwide markets. For example, cytostatic hormones had worldwide sales of approximately 1.8 biUion in 1994. Included in these 1.8 biUion are several steroids or steroid-mimetics such as megestrol acetate and tamoxifen (282), respectively (262). 

Hormone antagonists (tamoxifen and toremifen bind to the estradiol receptor, flutamide binds to the androgen receptor) are used for treating breast and prostate cancer. 

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. 

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. 

Options for adjuvant hormonal therapy in postmenopausal women include aromatase inhibitors (e.g. anastrozole, letrozole, or exemestane) either in place of or after tamoxifen. Adverse effects with aromatase inhibitors include hot flashes, myalgia/arthralgia, vaginal dryness/atrophy, mild headaches, and diarrhea. 

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. 

Jordan VC, Fritz NF, Tormey DC (1987a) Long-term adjuvant therapy with tamoxifen effects on sex hormone binding globulin and antithrombin III. Cancer Res 47 4517-4519... 

Finally, therapeutic sequencing of different hormonal agents is fast becoming a common clinical practice, and fulvestrant is a good treatment choice to extend the opportunity for using endocrine therapies before reliance upon cytotoxic chemotherapy is necessary. Further research is required in order to evaluate the optimal sequence, both in clinical practice as well as in the laboratory, to choose the correct treatment of breast cancer in each person after the appearance of tamoxifen-induced drug resistance (Robertson 2004 Osipo et al. 2004 Johnston 2004 Robertson et al. 2005). 

Willis KJ, London DR, Ward HW, Butt WR, Lynch SS, Rudd BT (1977) Recurrent breast cancer treated with the antioestrogen tamoxifen correlation between hormonal changes and clinical course. Br Med J 1 425-428... 

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