Hormone therapy breast cancer

B14. Burton, G., Flowers, J., Cox, E., Geisinger, K., Leight, G., Georgiade, G., Dent, G., and McCarty, K., Jr., Monoclonal antiestrogen receptor antibody (H222) in fine needle aspiration cytologies of breast cancer A predictive marker of response to hormonal therapy. Breast Cancer Res. Treat. 6, 164 (1985). 

Come SE, Borges VF. Role of fulvestrant in sequential hormonal therapy for advanced, hormone receptorpositive breast cancer in postmenopausal women. Clin Breast Cancer. 2005 6(suppl 1) S15-S22. 

Zoledronic acid has also been investigated in the prevention of cancer treatment-induced bone loss in 401 premenopausal women receiving adjuvant endocrine therapy for hormone-responsive breast cancer in a randomised, open-label. Phase 111 clinical trial [76]. In this study, patients received tamoxifen and goserelin with or without zoledronic acid (4 mg i.v. every 6 months) versus anastrozole and goserelin with or without zoledronic acid (4 mg i.v. every 6 months) for 3 years. The combination of zoledronic acid with endocrine therapy was well tolerated and was not associated with changes in renal function in this patient population. Over 3 years, 2, 904 serum creatinine measurements were taken, the mean serum creatinine level was 0.78 + 0.17 mg/ dl, and no patient had serum creahnine levels that exceeded 1.5 times the upper limit of normal [76]. 

Cline, J.M. and Hughes, C.L. Jr., 1998. Phytochemicals for the prevention of breast and endometrial cancer. In Biological and Hormonal Therapies of Cancer. Eds. K.A. Foon and H.B. Muss. Boston, MA Kluwer Academic Publishers. 

It must be stressed that hyperphosphatasemia in uncomplicated liver or bone disease, although of academic interest, has never posed a mystery of interpretation to the clinician nor has it confused the grounds for his decision making. The problem has arisen principally in dealing with laboratory findings in coexisting liver and bone disease, especially where a sudden elevation has occurred in the serum phosphatase level, as in hormonal therapy of cancer of the breast or of the prostate. 

Progestational agents see Chapter 57) have been used as second-tine hormonal therapy for metastatic hormone-dependent breast cancer and in the management of endometrial carcinoma previously treated by surgery and radiotherapy. In addition, progestins stimulate appetite and restore a sense of well-being in cachectic patients with advanced stages of cancer and AIDS. 

Tamoxifen (Tam) (Novaldex) is an estrogen receptor antagonist present in breast tissue, with activity linked to its metabolite hydroxytamoxifen (OHTam). In other tissues (endometrium) it behaves as an agonist due to the presence of other coactivators. This SERM is involved in the endocrine therapy commonly used with hormone-dependent breast cancers, although aromatase inhibitors (Anastrozole) are also frequently used for the same female patient group. Tamoxifen is the most common hormonal treatment for breast cancer in men. It also protects against osteoporosis [17]. 

Tamoxifen is the most widely used anti-oestrogen for the treatment of hormone-dependent breast cancer. The specific drug is used as a hormonal therapy for patients who exhibit ER+ breast cancer. The pharmacological activity of tamoxifen depends on its conversion to its active metabolite, endoxifen, by CYP2D6. Mechanisms of action and side effects have been recently revised [34 ]. 

The measurement of ER has become a standard assay in the clinical management of breast cancer. The presence of ERa identifies those breast cancer patients with a lower risk of relapse and better clinical outcome. Receptor status also provides a guideline for those tumors that may be responsive to hormonal intervention. But only about half of ER-positive patients respond to hormonal therapies. Of those who respond initially, most will eventually develop an estrogen unresponsive disease following a period of treatment even though ERa is often still present. Mutant receptors and constitutively active r eceptors as well as hormone-independent activation of the ERa are discussed. The involvement of ER 3 isoforms is under investigation. 

There is much interest in the possible hormonal effects of phytoestrogens in both men and women. The majority of studies conducted in women have examined the ability of phytoestrogens to alleviate menopausal symptoms. Whilst hormone replacement therapy is recommended for women experiencing menopausal symptoms, there remains some uncertainty as to whether HRT can increase the risk of breast cancer. As a result of these concerns, investigations into natural alternatives such as phytoestrogens have received considerable attention. 

CD Since the publication of the Women s Health Initiative study, there has been an increase in the use of non-hormonal therapies for the management of menopausal symptoms. Particularly for women with CHD and breast cancer risk factors, non-hormonal therapies may offer an alternative to assist with symptom management. A wide range of therapies, both prescription and herbal, have been studied with varying degrees of success. In choosing a particular therapy, it is important to match patient symptoms with a therapy that is not only effective but also safe. 

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. 

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%. 

An NIH Consensus Development Conference Statement22 advises that adjuvant hormonal therapy should be recommended to women whose tumors contain hormone-receptor protein regardless of age, menopausal status, involvement of axillary lymph nodes, or tumor size. They also support a benefit of adjuvant chemotherapy for most women with lymph node metastases or with primary breast cancers larger than 1 cm in diameter (both node-negative and node-positive).22... 

The use of preoperative systemic therapy is gaining favor in both early-stage and locally advanced breast cancers. This approach to therapy, referred to as neoadjuvant or primary systemic therapy, most often consists of chemotherapy but in special circumstances also may include hormonal therapy (e.g., in inoperable patients with significant comorbidities). The advantages of preoperative systemic therapy include... 

Hormonal therapies that have been studied in the treatment of primary or early breast cancer include antiestrogens, oophorectomy, ovarian irradiation, luteinizing hormone-releasing hormone (LHRH) agonists, and aromatase inhibitors. 

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... 

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