Arzoxifene: the evidence for its development in the management of breast cancer

INTRODUCTION: Endocrine therapy is an important and integral part of breast cancer management. Selective estrogen receptor modulators (SERMs), such as tamoxifen, remain a vital component in the endocrine therapy armamentarium. However the “ideal SERM”, which has antagonist effects on the breast and endometrium but beneficial agonistic effects on bone and lipid profile, remains to be found. AIM: The aim of this review is to examine the evidence for arzoxifene as the “ideal SERM.” EVIDENCE REVIEW: Arzoxifene showed initial promise as the “ideal SERM” in preclinical, phase I, and phase II clinical studies. It appeared to have powerful antiestrogenic effects on breast cancer and endometrium, with equally strong favorable estrogenic effects on bone and lipid profile, minimal side effects, and good oral bioavailability. However, phase III trial data found it to be inferior to tamoxifen, bringing an apparent end to its investigation as a breast cancer treatment. CLINICAL POTENTIAL: Despite early promise as the “ideal SERM”, results from a phase III trial have relegated arzoxifene to research in breast cancer prevention and osteoporosis treatment.