Neoadjuvant treatment of endometrial cancer using anastrozole: a randomised pilot study.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
St. James University Hospital, Beckett Street, Leeds LS9 7TF, UK. Electronic address: amudha.thangavelu@nuh.nhs.uk.
Amudha
A
Thangavelu
Matthew J
MJ
Hewitt
Naomi D
ND
Quinton
Sean R
SR
Duffy
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077384:Anastrozole; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D047072:Aromatase Inhibitors / Q000627:therapeutic use; D048708:Cell Growth Processes / Q000187:drug effects; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D047628:Estrogen Receptor alpha / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009570:Nitriles / Q000627:therapeutic use*; D010865:Pilot Projects; D010919:Placebos; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000096:biosynthesis; D014230:Triazoles / Q000627:therapeutic use*
D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D019394:Ki-67 Antigen; D009570:Nitriles; D010919:Placebos; D019253:Proto-Oncogene Proteins c-bcl-2; D011980:Receptors, Progesterone; D014230:Triazoles; D000077384:Anastrozole
Anastrozole; Aromatase inhibitors; Endometrial neoplasms; Endometrium