Introduction

Endocrine therapy plays a crucial role in the systemic treatment of hormone receptor-positive breast cancer. The selective estrogen receptor (ER) modulator tamoxifen is widely used as a treatment for ER positive breast cancer and for risk reduction. However, tamoxifen possesses both antagonistic and agonist effects on the ER (1,2). Fulvestrant, a pure ER antagonist, was initially developed to overcome the agonist-based limitations of tamoxifen and to treat tamox-ifen-resistant tumors. Further, fulvestrant may modulate the interaction between the ER and growth factor signaling pathways by downregulating ER expression. This action may be important in developing an optimal strategy for using endocrine therapy—in sequence, in combination, or paired with other biologically targeted agents. This chapter reviews the pharmacological properties of fulvestrant, evaluates the preclinical and clinical data, and describes the role of fulvestrant today in the context of other available hormonal and biologic therapies.

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