Endocrine therapy

Buzdar AU (2005—2006) Aromatase inhibitors changing the face of endocrine therapy for breast cancer. Breast dis 24 107-117... 

Determine appropriate indications for endocrine therapy, chemotherapy, and biologic therapy for patients with metastatic breast cancer. 

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. 

The choices of chemotherapy regimen, dose, schedule, and duration of therapy, as well as the choice of endocrine therapy, are controversial and rapidly changing as results from ongoing randomized clinical trials are reported. 

Endocrine therapy is primary therapy for endocrine-responsive disease, with chemotherapy being added for some intermediate- and all high-risk patients... 

Both endocrine therapy and chemotherapy are used in patients with an uncertain endocrine response category unless the patients are low risk, in which case they may just try endocrine therapy alone. 

The goal of therapy with early and locally advanced breast cancer is to cure the disease. Breast cancer is currently incurable after it has advanced beyond local-regional disease. The goal of treatment of metastatic breast cancer is to improve symptoms, maintain quality of life, and extend survival. Thus it is important to choose therapy with good activity while minimizing toxicities. Treatment of metastatic breast cancer with either cytotoxic or endocrine therapy often results in regression of disease and improvements in quality of life. 

The choice of therapy for metastatic disease is based on the site of disease involvement and presence or absence of certain characteristics (i.e., hormonal status of the primary tumor and disease location). For example, patients who experience a long DFS following local-regional therapy or have disease that is located primarily in the bone or soft tissue likely will respond to endocrine therapy. Patients with asymptomatic visceral involvement (e.g., liver or lung) may be candidates for hormonal therapy depending on the clinical circumstance (generally... 

Until recently, there was little evidence that the response or survival benefit from one endocrine therapy was clearly superior to that achieved with other therapies. Given this equality in efficacy, the choice of a particular endocrine therapy was based primarily on toxicity (Table 86-8). Based on these criteria, tamoxifen is the preferred initial agent when metastases are present. An exception to this occurs when the patient is receiving adjuvant tamoxifen at the time or within 1 year of occurrence of metastatic disease. 

TABLE 86-8. Endocrine Therapies Used for Metastatic Breast Cancer... 

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. 

There are no well-defined clinical characteristics or established tests to identify patients likely to benefit from chemotherapy. Factors associated with an increased probability of response that have been identified include a good performance status, a limited number (one to two) of disease sites, and patients who respond to chemotherapy or hormonal therapy with a long disease-free interval. Patients who have progressive disease during chemotherapy have a lower probability of response to a different type of chemotherapy. However, this is not necessarily true for patients who are given chemotherapy after some interval during which they have received no chemotherapy. Patients who do not respond to endocrine therapy are as likely to respond to chemotherapy as patients who are treated with chemotherapy as their initial treatment modality. Age, menopausal status, and receptor status have not been associated with favorable or unfavorable response to chemotherapy. 

For women whose breast cancer has metastasized to bone, bisphosphonates are recommended, in addition to chemotherapy or endocrine therapy, to reduce bone pain and fractures.28,64 Pamidronate (90 mg) and zoledronate (4 mg) can be given intravenously once each month. These bisphosphonates are given in combination with calcium and vitamin D. 

Educate the patient on the chemotherapy or endocrine therapy regimen chosen for the patient, focusing on what adverse events to expect, when to expect them, and how to manage them if they do occur. Also include in the initial education an overall plan of care, including the duration of therapy, other treatment modalities that will follow (e.g., radiation therapy, surgery, endocrine therapy), and when the patient will receive them. 

Develop a pre- and postmedication plan for the chemotherapy or endocrine therapy regimen chosen... 

Determine success of the overall treatment plan by obtaining a thorough history of adverse events experienced with the previous chemotherapy/endocrine therapy treatment and objective measures of response to therapy. Assess effects on quality-of-life measures such as physical, psychological, and social function and well-being. 

Patients must be monitored to assess their response to treatment and to detect recurrent diseases. PSA as a specific marker for prostate cancer is most useful in monitoring patients who have been treated with radical prostatectomy, radiation therapy, or endocrine therapy. The concentration of PSA falls to undetectable levels following a radical prostatectomy because all prostate tissue has been removed. Generally, PSA is measured at periodic intervals. In studies, the extent of disease at the time of surgery correlated well with the postoperative PSA concentration. A significant measurable PSA concentration after prostatectomy indicates that residual tumor may be present. PSA concentrations decline gradually after radiation therapy (36). 

Tamoxifen has been the gold standard for adjuvant endocrine therapy. It has both estrogenic and antiestrogenic properties, depending on the tissue and gene in question. 

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. 

Patients are sequentially treated with endocrine therapy until their tumors cease to respond, at which time chemotherapy can be given. 

Historically, the choice of an endocrine therapy was based primarily on toxicity and patient preference but study results have led to changes in MBC treatment (Table 61-2). 

Ovarian ablation (oophorectomy) is considered by some to be the endocrine therapy of choice in premenopausal women and produces similar overall response rates as tamoxifen. Medical castration with an LHRH analog, goserelin, leuprolide, or triptorelin, is a reversible alternative to surgery. 

Chemotherapy is preferred to endocrine therapy for women with hormone receptor-negative tumors rapidly progressive lung, liver, or bone marrow involvement or failure of endocrine therapy. 

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). 

Howell A, Robertson JFR, Abram P, Lichinitser MR, Elledge R, Bajetta E, Watanabe T, Morris C, Webster A, Dimery I, et al. (2004a) Comparison of fulvestrant versus tamoxifen for the treatment of advanced breast cancer in postmenopausal women previously untreated with endocrine therapy a multinational, double-blind, randomized trial. J Clin Oncol 22 1605-1613... 

Morris C, Wakeling A (2002) Fulvestrant ( Faslodex )-a new treatment option for patients progressing on prior endocrine therapy. Endocr Relat Cancer 9 267-276... 

Osborne CK, Pippen J, Jones SE, Parker LM, Ellis M, Come S, Gertler SZ, May JT, Burton G, Dimery I, et al. (2002) Double-blind, randomized trial comparing the efficacy and tolerability of fulvestrant versus anastrozole in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy results of a North American trial. J Clin Oncol 20 3386-3395... 

Q79 Tamoxifen is an oestrogen-receptor antagonist that is only effective as adjuvant endocrine therapy of early breast cancer in postmenopausal v/omen. Tamoxifen is given by mouth and treatment should not exceed 1 year. 

In addition, it will be our intention to present a deeper insight into the biosynthesis of steroid hormones, which will allow definition of new targets and approaches for the treatment of endocrine-responsive cancer. Enzymes involved in mechanisms of steroid hormone biosynthesis might be novel targets for endocrine therapy. Moreover, further therapeutic indications for modulators of steroid hormone receptors will be discussed. In summary, many promising new opportunities for endocrine therapy of breast and prostate cancer are now arising. 

Anti-hormone Therapy Principles of Endocrine Therapy of Cancer... 

Endocrine therapy of cancer is based on at least one of the following principles ... 

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