Hormonal therapy breast cancer response

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). 

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. 

Cytotoxic chemotherapy is eventually required in most patients with metastatic breast cancer. Patients with hormone-receptor-negative tumors require chemotherapy as initial therapy of symptomatic metastases. Patients who respond initially to hormonal manipulations eventually cease to respond and go on to require chemotherapy. The median duration of response is 5 to 12 months, but some patients will have an excellent response to an initial course of chemotherapy and may live 5 to 10 years or longer without evidence of disease. In general, median survival of patients after treatment with commonly used drug combinations for metastatic breast cancer is 14 to 33 months. The median time to response has ranged from 2 to 3 months in most studies, but this period depends in large part on the site of measurable disease. The median time to appearance of response is between 3 and 6 weeks in patients whose disease is primarily in the skin and lymph nodes, 6 to 9 weeks in patients with metastatic lung involvement, 15 weeks in patients with hepatic involvement, and nearly 18 weeks in patients with bone involvement. Thus it is often the case that an immediate response to therapy is not... 

Metastatic cancer- May be used secondarily in women with advancing inoperable metastatic (skeletal) breast cancer who are 1 to 5 years postmenopausal. Primary goals of therapy include ablation of the ovaries. This treatment has been used in premenopausal women with breast cancer who have benefited from oophorectomy and have a hormone-responsive tumor. 

The successful response of breast cancers to tamoxifen or progestin treatment depends on the presence of high-affinity receptors for estrogen, progesterone, or both. Fewer than 10% of mammary tumors that lack detectable ER levels will respond to hormonal therapies. Determination of hormone receptor levels in tumor samples is highly recommended before selecting a therapy. 

Most steroid-sensitive cancers express specific cell surface receptors. Prednisone-sensitive lymphomas, estrogen-sensitive breast cancers, and prostatic cancers express specific receptors for corticosteroids, estrogens, and androgens, respectively. It is now possible to assay tumor specimens for steroid receptor content and to identify which individual patients are likely to benefit from hormonal therapy. Measurement of the estrogen receptor (ER) and progesterone receptor (PR) proteins in breast cancer tissue is now standard clinical practice. ER or PR positivity predicts response to hormonal therapy, whereas patients whose tumors are ER-negative generally fail to respond to such treatment. 

A variety of studies have shown that 10% to 20% of the population of developed countries have marginal or inadequate stams, as assessed by erythrocyte transaminase activation coefficient (Section 9.5.36) or plasma pyridoxal phosphate (Section 9.5.1 Bender, 1989b). This may be sufficient to enhance the responsiveness of target tissues to steroid hormones (Section 9.3.3), and may be important in the induction and subsequent development of hormone-dependent cancer of the breast and prostate. Vitamin Be supplementation may be a useful adjunct to other therapy in these common cancers certainly, there is evidence that poor vitamin Be nutritional stams is associated with a poor prognosis in women with breast cancer. 

Systemic chemotherapy is usually not indicated in non-colorectal liver metastases due to lack of response. The systemic administration of cytostatics (also in combination) possesses the status of palliative therapy. However, in metastatic neuroendocrine tumours, a combination of octreotide -i- IFN had a positive effect on the survival time. Systemic chemotherapy produced remission rates of up to 60%. (320) In metastatic breast cancer, systemic chemotherapy is indicated, usually in combination with hormonal and immune therapy. (316, 342) In metastatic gastric carcinoma, palliative chemotherapy can achieve a remission rate of up to 40%, with a slight extension of survival time. 

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]. 

Amplification of HER-2/neu is found in breast, ovarian, and gastrointestinal tumors. In breast cancer, it appears to be as useful a prognostic indicator of overall survival as tumor size or ER and PR expression, but not as good as the number of lymph nodes involved in metastases. Elevated serum HER-2/neu antigen levels have been shown to correlate witli decreased response to hormone therapy of breast cancer. Of the three oncogenes—HER-2/ e , ras, and c-myc— HER-2/neu has the strongest prognostic value in breast cancer. 

HER-2/new in patients with ER-positive cancers showed significantly worse clinical benefit from hormonal therapies. Furthermore, the study showed a trend toward improved outcome with aromatase inhibitors for patients with elevated serum HER-2/ e , Serum levels of HER-2/ne are also useful in monitoring breast cancer patients because the HER-2/ttew levels decrease in response to treatment. Her-ceptin treatment is now administered only to those breast cancer patients who have HER-2/ e amplification. 

Lipton A, Ali SM, Leitzel K, et al. Elevated serum Her-2/neu level predicts decreased response to hormone therapy in metastatic breast cancer. J Cfin Oncol 2002 20 1467-72. 

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