Evaluation of neoadjuvant inhibition of aromatase activity and signal transduction in breast cancer

Purpose: To evaluate the efficacy and safety of combing aromatase inhibitor (At) and signal transduction inhibitor neoadjuvantly in postmenopausal patients with invasive hormone-sensitive breast cancer. Patients and methods: Postmenopausal women with hormone-sensitive breast cancer were given three months of letrozole 2.5 mg daily and imatinib 400 mg twice daily preoperatively. End-points of this study included clinical and pathologic responses, toxicities, and change in [F-18]fluorodeoxyglucose (FDG) uptake in tumor. Expression of c-Kit was also evaluated in breast cancer tissue by immunostaining. Results: Thirteen patients, aged 52-78, were accrued. Five patients (38.5%) experienced grade 3 toxicity including neutropenia, skin rash, dermatitis, hypokalemia, shortness of breath, acute coronary syndrome, and acute chronic gastritis. Three patients were withdrawn after two months of treatment due to hematoma in tumor and toxicity. Of the ten evaluable patients, nine patients (90%) achieved clinical partial response and one patient (10%) had stable disease. One patient (10%) achieved pathologic complete response. Average relative changes of FDG uptake was -69.5% among responders. Eight out of 13 tissue samples were tested for c-Kit expression and the expression was detected in all. Conclusions: In this pilot study, the dramatic response to this ncoadjuvant combination treatment warrants further clinical trials. Further investigation on the involvement of c-Kit pathway in the treatment response is also suggested. However, dosage reduction of imatinib may be required to avoid its potential toxicity. (C) 2007 Elsevier Ireland Ltd. All rights reserved.