Role of Fulvestrant in The Treatment of Metastatic Breast Cancer in Premenopausal Women

Hormone receptor-positive breast cancer is the most common presentation of breast cancer today. Endocrine therapy is the preferred treatment modality in hormone receptor-positive early stage and advanced breast cancer.

Fulvestrant is an estrogen receptor antagonist indicated for the treatment of postmenopausal women with estrogen receptor-positive, locally advanced or metastatic breast cancer for disease relapse on or after adjuvant antiestrogen therapy, or disease progression on therapy with an antiestrogen.

Fulvestrant is a selective estrogen receptor down-regulator that competitively binds to estrogen receptors, with a binding affinity approximately 100 times greater than that of tamoxifen. Once bound to the receptor, estrogen receptor dimerization and nuclear translocation are inhibited, resulting in accelerated receptor degradation. Besides the nuclear estrogen receptor, fulvestrant blocks cytoplasmatic as well as membrane-bound receptors. It is therefore suggested that fulvestrant inhibits the estrogen receptor/growth factor crosstalk responsible for estrogen receptor activation in the absence of estrogen.

In premenopausal women, the combination of gonadotropin-releasing hormone analogues and tamoxifen is a standard of care for premenopausal women with endocrine-responsive metastatic breast cancer. Upon disease progression, selected patients may be candidates for further endocrine treatment in combination with ongoing ovarian function suppression.

Several preclinical studies have demonstrated that fulvestrant was markedly more effective than tamoxifen in inhibiting the in vitro growth of human breast carcinoma cells and was also effective in tamoxifen-resistant breast carcinoma xenografts in vivo mouse models.