Use of Aromatase Inhibitors in Advanced Endometrial Cancer

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This article reviews the current evidence for the role of aromatase inhibitors (AIs) in the treatment of advanced stage or recurrent endometrial cancer.
This article reviews the current evidence for the role of aromatase inhibitors (AIs) in the treatment of advanced stage or recurrent endometrial cancer.

Abstract

Objectives: Women with advanced or recurrent endometrial cancers have a limited panel of options for treatment. Given the fact the majority of endometrial cancers are estrogen dependent, AIs have been hypothesized as an option for treatment. This article reviews the current evidence for the role of aromatase inhibitors (AIs) in the treatment of advanced stage or recurrent endometrial cancer.

Methods: We performed a systematic literature review of the use of AIs in advanced or recurrent endometrial cancers.

Results: A number of phase 2 trials and case reports have shown minimal activity of single agent AIs, with equivocal evidence for response based on ER status. One recent study shows promise in the combination of AIs with mTOR inhibitors.

Conclusions: AIs show little promise as single agent treatment for advanced or recurrent endometrial cancer, but in combination with other novel therapies such as targeted therapies, they have potential to offer good response rates.

Introduction

Endometrial carcinoma (EC) is the most prevalent type of gynecological malignancy in women in the United States, with an estimated 60,000 new cases to be diagnosed in 2016.1 ECs are classified into 2 types. Type I EC is estrogen-dependent with endometrioid histology, carries a better prognosis, and represents over 80% of these cancers. In comparison, type II EC is non-estrogen-dependent, presenting with higher risk histologic patterns with a 5-year survival of 53% to 62%.2

Estrogen is a hormone that contributes to the proliferation of the uterine endometrium, which may lead to endometrial hyperplasia and subsequently, neoplasia. Aromatase is a cytochrome P450 enzyme that converts androgens to estrogens and is present in the ovaries, placenta, and many peripheral tissues, including adipose. In postmenopausal women, the action of aromatase produces the majority of circulating estrogen.3 Studies have shown that endometrial tumor stroma express greater amounts of aromatase compared to normal endometrium, hypothesized to function through a paracrine mechanism.4 AIs act to block the action of the enzyme, and have been show to suppress up to 95% to 98% of all circulating estrogens.5

Advanced and recurrent endometrial cancers have a poor prognosis regardless of type, and there is little consensus on the treatment of these cancers. The mainstay of treatment involves surgery or chemotherapy and radiation. Hormonal therapies targeting estrogen production have been used in patients with advanced or recurrent type I disease as an alternative for those who cannot tolerate the risks of other treatment modalities.6 Given the action of aromatase as the primary source of estrogen in postmenopausal women, it is theorized that its inhibition would be effective in the treatment of EC. This review explores the current evidence on the use of AIs in advanced or recurrent EC.

Sources and Study Collection

A systematic review using the National Library of Medicine (PubMed) Database was performed to identify articles. Articles were published in the English language between 1990 and 2016. Key words used in the search included “aromatase inhibitor”, “endometrial cancer”, and “recurrent”, and their combinations. Studies included prospective and retrospective trials and reports on single cases. Abstracts of all potentially-relevant studies were reviewed by the authors for inclusion.

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