Hormone therapy cancer

Modem cancer therapy has been primarily dependent upon surgery, radiotherapy, chemotherapy, and hormonal therapy (72) (see Chemotherapeutics,anticancer Hormones Radiopharmaceuticals). Chemotherapeutic agents maybe able to retard the rate of growth, but are unable to eradicate the entire population of neoplastic cells without significant destmction of normal host tissue. This serious side effect limits general use. More recentiy, the immunotherapeutic approach to cancer has involved modification and exploitation of the cellular and molecular mechanisms in host defense, regulation of tissue proliferation, tissue differentiation, and tissue survival. The results have been more than encouraging. 

Therapeutic Function Estrogen used in hormone therapy for prostate cancer Chemical Name 4,4 -(1,2-Diethyl-1,1-ethenediyl)bisphenol-bis(dihydrogen phosphate) Common Name Fosfestrol Structural Formula ... 

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. 

Besides the hormone therapy, the notion of targeted cancer therapy is not so new and can be traced back to the 1940 s [2]. Early approaches included the largely unsuccessful use of antibodies, often conjugated with radioisotopes or toxins, directed against tumor-associated antigens. 

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. 

Hormonal therapies have shown activity in the treatment of cancers whose growth is affected by gonadal hormonal control. Hormonal treatments either block or decrease the production of endogenous hormones. 

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

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... 

Early breast cancer is resected completely with curative intent, and adjuvant chemotherapy and hormonal therapy are initiated to prevent recurrence. During adjuvant chemotherapy, laboratory values to monitor chemotherapy toxicity are obtained prior to each cycle of chemotherapy. After completion of adjuvant therapy, patients are monitored every 3 months for the first few years after diagnosis, with intervals between exams extended as time from diagnosis lengthens. 

Metastatic breast cancer is not curable, and therapy is intended to palliate symptoms. In most cases, hormonal therapy is the mainstay. While on therapy, patients are monitored monthly for signs of disease progression or metastasis to common sites, such as the bones, brain, or liver. 

Prostate cancer treatment depends on the stage, age, Gleason score, and PSA concentration. Treatment options include expectant management, radiation therapy, radical prostatectomy, hormonal therapy, and chemotherapy. 

Oh WK. Secondary hormonal therapies in the treatment of prostate cancer. Urology 2002 60(3 suppl 1) 87—92. 

CA 15-3 serum tumor marker is intended to detect disease recurrence in stage II and stage III breast cancer patients. It has been reported that CA 15-3, together with other suitable markers, is preferred in measuring the effect of applied hormonal therapy or chemotherapy in metastatic disease. Studies have indicated that CA 15-3 assay values are frequently elevated in patients with breast cancer. These... 

Bubendorf L et al. Hormone therapy failure in human prostate cancer analysis by complementary DNA and tissue microarrays. J Natl Cancer Inst 1999 91 1758-1764. 

Low-dose hormone therapy (conjugated equine estrogen 0.45 mg and medroxyprogesterone acetate 1.5 mg/day) has demonstrated equivalent symptom relief and bone density preservation without an increase in endometrial hyperplasia. Whether such lower doses will be safer (cause less venous thromboembolism and breast cancer) remains to be seen. 

Alternatives to estrogen for hot flushes are shown in Table 31-6. Progesterone alone may be an option in women with a history of breast cancer or venous thrombosis, but side effects limit their use. For women with contraindications to hormone therapy, selective serotonin reuptake inhibitors and venlafaxine are considered by some to be first-line therapy, but efficacy of venlafaxine beyond 12 weeks has not been shown. 

The WHI study was the first randomized, controlled trial to confirm that hormone therapy reduces colon cancer risk. 

The Million Women Study reported that current use of hormone therapy increased breast cancer risk and breast cancer mortality. Increased incidence was observed for estrogen only, estrogen plus progestogen, and for tibolone. 

Combined hormone therapy may increase the risk of ovarian cancer, but more study is needed to confirm these findings. 

With estrogen-based therapy, there should be yearly breast exams, monthly breast self-examinations, and periodic mammograms. Women on hormonal therapy should undergo annual monitoring, including pelvic examination, blood pressure checks, and routine endometrial cancer surveillance. 

TABLE 65-1 Comparative Costs of Hormonal Therapy for Advanced Prostate Cancer ... 

Johnell O, Cauley JA, Kulkarni PM, Wong M, Stock JL (2004) Raloxifene reduces risk of vertebral fractures and breast cancer in postmenopausal women regardless of prior hormone therapy. J Fam Pract 53 789-796... 

Purdie D, Cauley J, Disch D et al. (2004) Effect of raloxifene on incidence of invasive breast cancer in postmenopausal women having a history of prior hormone therapy use results of the CORE trial Abstract. European Society of Medical Oncology (ESMO), Vienna... 

According to results from clinical trials, the agonistic effects of tamoxifen detected in animals were also observed in the human uterus as it produces a trophic effect and an increase in the incidence of endometrial pathology, which is related to endometrial thickening (> 4 mm). Its use seems to be associated with an increase in endometrial cancer, which is related to the length of treatment and the accumulated dose of tamoxifen. Nevertheless, these tumors do not seem to be more aggressive or to have a worse prognosis than those found in women who do not follow this treatment or who receive hormone therapy. 

Jenkins V, Shilling V, Fallowfield L, Howell A, Hutton S (2004) Does hormone therapy for the treatment of breast cancer have a detrimental effect on memory and cognition A pil study. Psychooncology 13 61-66... 

Hormone therapy has proven highly effective in controlling the menopausal syndrome, especially severe hot flushes (MacLennan et al. 2004), even at doses significantly lower than those used until now (Speroff et al. 2000 Utian et al. 2001). Women s Health Initiative studies found that hormone replacement therapy, when administered as a primary prevention intervention for CVD in older women, increases the risk of heart disease and breast cancer. Even if a protective effect on fracture and colon cancer was observed, the risk-benefit ratio led to a recommendation of this treatment only for the short-term relief of menopausal symptoms (Rossouw et al. 2002 Anderson et al. 2004). The role of early administration of ovarian hormones to young postmenopausal women in the prevention of cardiovascular disease or late dementia remains... 

Jordan VC, Furr BJA (eds) (2002) Hormone therapy in breast and prostate cancer. 

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