Fulvestrant: Neue Therapieoption beim hormonsensiblen, fortgeschrittenen Mammakarzinom

Abstract

Endocrine therapy with agents that reduce estrogen levels or block the estrogen receptor remains an important motility in breast cancer management. Recently, a number of alternative endocrine treatments have been developed, including several selective estrogen receptor modulators (SERMs), aromatase inhibitors (AI) and most recently the estrogen receptor downregulator Fulvestrant. Fulvestrant is a new type of endocrine treatment, an estrogen receptor (ER) antagonist with no agonist effects. Fulvestrant down-regulates cellular levels of the ER, resulting in decreased expression of the progesterone receptor. Preclinical and early clinical data suggest a novel mode of action which may result in a different clinical profile from that of Tamoxifen and related compounds. In post-menopausal patients with hormone sensitive, advanced breast cancer the efficacy of Fulvestrant has been proven in phase III trials. These second line trials showed a comparable efficacy of Fulvestrant to that of the third generation aromatase inhibitor Anastrozol. A recently published first line comparison between Tamoxifen and Fulvestrant in hormone sensitive, metastatic breast cancer indicated that Fulvestrant only offered an advantage in ER and PR positive tumours. Fulvestrant has shown efficacy when used after progression after Tamoxifen or aromatase inhibitors have been administered in post-menopausal women with metastatic breast cancer. It is also known that subsequent endocrine treatments after progression with prior Fulvestrant administration demonstrated no cross resistance between Fulvestrant and other endocrine therapies. In summary, Fulvestrant represents an additional anti-estrogen for the treatment of post-menopausal women with advanced breast cancer. The place of Fulvestrant within the sequential endocrine cascade in metastatic breast cancer needs to be evaluated in future studies.