Anti-proliferative and molecular effects of neoadjuvant (pre-operative) gefitinib alone or in combination with anastrozole in epidermal growth factor receptor (EGFR) positive, estrogen receptor alpha (ERα) positive patients with primary breast cancer

552 Background: We conducted a study to determine the effects of EGFR inhibition with or without aromatase inhibition, on the growth of primary breast cancer. Estrogen and epidermal growth factor phosphorylate ERα via MAPK. This trial used inhibition of EGFR alone vs ER + EGFR inhibition in ER+/ EGFR+ breast cancer to determine the role for EGFR in modulating both the Ser118 phosphorylated (p) state of ERα and downstream events (cell proliferation (Ki67) / tumour size). Methods: 53 untreated postmenopausal patients with ER+/EGFR+ primary breast cancer were randomised to 4 wks neoadjuvant therapy with gefitinib (Iressa) alone (Group A) or gefitinib + anastrozole (Group B) in a controlled double-blind trial. Biopsies were collected before & after 4 wks treatment. Expression of Ki-67, pEGFR (Y845), MAPK, AKT and pERα (S118) was assessed by immunohistochemistry in paired samples. Tumour size and pharmacokinetics were also evaluated. Results: Ki67 was reduced by 77.3 and 93.2% in Groups A and B respectively, i...