Fulvestrant in the management of postmenopausal women with advanced, endocrine-responsive breast cancer

Fulvestrant is a pure estrogen antagonist that binds, blocks and downgrades the estrogen receptor (ER). Its unique mechanism of action is its antitumor activity after progression on prior endocrine therapy. Fulvestrant has shown activity in ER-dependent cells that are ligand independent. Fulvestrant has been approved at 250 mg/month for postmenopausal women with hormone-sensitive advanced breast cancer after progression or recurrence on antiestrogen therapy. The fulvestrant 500 mg regimen has just received approval by the EMA and the US FDA, supported by dose-dependent ER downregulation and the recent results of the clinical trial CONFIRM. Fulvestrant in combination with systemic lowering of estrogen has shown no improvement over fulvestrant alone. Combination therapy with inhibitors of growth factor signaling may have greater efficacy and is under exploration. To enhance the benefit of fulvestrant and improve outcomes for individuals with ER-positive breast cancer, greater understanding of resistance mechanisms is required. A key issue is identification of patients with ER-positive disease who retain sensitivity to antiestrogen therapy after progression on tamoxifen and/or aromatase inhibitors.