engleski

Other possibilities of hormone therapy in the therapy of breast cancer: fulvestrant and LHRH agonists.

Endocrine therapy has an important and even dominant role in the treatment of patients with hormone-sensitive breast carcinoma. The aim of endocrine therapy is to counteract estrogen’ s trophic effects (predominantly proliferative) on breast cancer cells. These estrogen effects are predominantly mediated through specific nuclear estrogen receptors (ER). The determination of the ER and progesterone receptor (PR) status of breast cancer should be the obligatory and/or routine task in clinics since a positive ER status indicates a probable positive response to the endocrine therapy. Moreover, a positive receptor status correlates with favorable prognostic features, such as a lower rate of tumor cell proliferation and histological evidence of tumor differentiation. Tumors that express both ER and PR have the greatest benefit from hormonal therapy, but those containing only ER or PR still have significant responses. Hormonal therapy in these types of breast carcinoma is likely to be effective, the side effects are of minimal toxicity and thus breast cancer patients have a satisfactory quality of life. In recent years a number of advances have been made in both metastatic and adjuvant therapy (Pritchard KI. Clin Cancer Res 2003). The aim of this topic is to present the role of and the results obtained with the new ER down-regulator fulvestrant (Faslodex) and with the luteinizing hormone releasing hormone (LHRH) analogues in the premenopausal patients in the management of breast cancer. Fulvestrant is a new ER antagonist that, unlike tamoxifen, is devoid of agonistic activities. Its binding to the ER induces a rapid loss of ER protein from breast carcinoma cells. Also, when compared with tamoxifen, fulvestrant consistently reduces tumor PR content. In clinical studies fulvestrant has been most commonly studied as an i.m. injection of 250 mg once monthly. Phase II trial showed that fulvestrant was effective in women who had breast carcinoma that progressed after tamoxifen therapy, (lack of cross-resistance to tamoxifen) and that there were no major safety of toxicity issues in the use of this drug. Subsequently, it was tested in two Phase III clinical trials (0020 and 0021), where it was compared with anastrozole in a total of 851 postmenopausal women with advanced breast cancer (ABC) that had relapsed or progressed after endocrine therapy. The combined data from these two studies has shown that fulvestrant was at least as effective as anastrozole in the second-line treatment of patients with ABC and was also well tolerated. Furthermore, a publication with the Phase III trial has recently appeared (Howell A. J Clin Oncol 2004.) in which fulvestrant was compared with tamoxifen in first-line treatment of ABC in 587 postmenopausal women. Fulvestrant showed similar activity as tamoxifen. In the context of results obtained with tamoxifen and aromatase inhibitors (AI) and due to the lack of cross-resistance fulvestrant has a role in an endocrine cascade treatment of breast cancer. LHRH agonists in premenopausal women cause reversible ovarian castration by suppressing LH production. Their use in patients with endocrine responsive breast tumors (predominantly goserelin, with tamoxifen or with AI) is clinically beneficial (Sainsbury R. Surg Oncol 2003). In postmenopausal women where ovarian estrogen biosynthesis naturally ceases other anti-estrogen treatments (tamoxifen, AI, fulvestrant) are indicated in suppressing the action of nonovarian-produced estrogens.

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