St. James University Hospital, Beckett Street, Leeds LS9 7TF, UK.
Gynecol Oncol. 2013 Dec;131(3):613-8. doi: 10.1016/j.ygyno.2013.09.023. Epub 2013 Sep 27.
Excessive oestrogenic stimulation is a well-known risk factor for the development and progression of endometrial cancer. Aromatase is the key enzyme which catalyses the conversion of androgens to oestrogens in postmenopausal women. Inhibition of aromatase may therefore be a useful strategy in the management of endometrial cancer. A pilot study was designed to assess the feasibility of a neoadjuvant model and understand the biological effects of anastrozole, an aromatase inhibitor, in the treatment of endometrial cancer.
Patients with endometrial cancer who consented to participate in the study were randomised to receive anastrozole or placebo for a minimum of 14 days prior to definitive surgery. Endometrial samples were obtained before and after treatment. Immunohistochemistry was performed to ascertain the expression of oestrogen receptor alpha (ERα), progesterone receptor (PR), androgen receptor (AR), ki-67 and Bcl2 before and after treatment in glands and stroma of the endometrium.
A total of 16 patients were randomised to the anastrozole arm and 8 to the placebo arm (2:1 randomisation). A significant decrease in the glandular expression of ERα and AR was observed in the anastrozole arm. There was no significant change in the expression of PR or Bcl2. Expression of ki-67, a proliferation marker, also decreased significantly following treatment with anastrozole.
Treatment with anastrozole caused a significant decrease in proliferation as demonstrated by decreased ki-67 expression. A large randomised controlled trial is warranted to fully assess the role of anastrozole in the neoadjuvant treatment of endometrial cancer.
雌激素过度刺激是子宫内膜癌发生和进展的已知危险因素。芳香酶是绝经后妇女将雄激素转化为雌激素的关键酶。因此,抑制芳香酶可能是治疗子宫内膜癌的一种有用策略。设计了一项初步研究,以评估新辅助模型的可行性,并了解芳香酶抑制剂阿那曲唑在治疗子宫内膜癌中的生物学作用。
同意参与研究的子宫内膜癌患者被随机分为阿那曲唑或安慰剂组,在明确手术前至少接受 14 天的治疗。在治疗前后获得子宫内膜样本。进行免疫组织化学染色,以确定治疗前后子宫内膜腺体和基质中雌激素受体α(ERα)、孕激素受体(PR)、雄激素受体(AR)、ki-67 和 Bcl2 的表达。
共有 16 名患者被随机分配到阿那曲唑组,8 名患者被分配到安慰剂组(2:1 随机分组)。在阿那曲唑组中观察到 ERα 和 AR 表达在腺体中的显著降低。PR 或 Bcl2 的表达没有显著变化。增殖标志物 ki-67 的表达在接受阿那曲唑治疗后也显著下降。
阿那曲唑治疗导致增殖显著减少,这表现为 ki-67 表达减少。需要进行大规模的随机对照试验来充分评估阿那曲唑在子宫内膜癌新辅助治疗中的作用。