Aromatase inhibition: a potential target for the management of recurrent or metastatic endometrial cancer by letrozole: more questions than answers?

INTRODUCTION

Endometrial cancer generally presents as early and resectable disease, but about 20% of patients present with either incurable or recurrent/metastatic disease. Patients with good performance status will be treated with hormonal agents, including progestins and tamoxifen, followed by cytotoxic chemotherapy. The options are restricted to hormonal agents for those with multiple comorbidities and older age. Therefore, there is a need to identify novel hormonal agents and other targeted therapeutics with improved therapeutic window in this setting.

AREA COVERED: Clinical trials of letrozole in localized and metastatic settings are reviewed. In the localized setting, limited by the small sample size, preliminary and conflicting clinical activities were observed. Despite the selection of Type I endometrial cancer, which is more estrogen-dependent for its growth, modest clinical activity was observed in the metastatic setting. Thus far, no biomarkers for efficacy have been identified.

EXPERT OPINION: Further understanding of the relevance of aromatase and estrogen receptor and their interplay with other growth pathways will be necessary to guide further development of letrozole. It is premature to declare letrozole a therapeutic option in recurrent/metastatic endometrial cancer.