Evaluation of neoadjuvant inhibition of aromatase activity and signal transduction in breast cancer.
OBJECTIVE
To evaluate the efficacy and safety of combing aromatase inhibitor (AI) and signal transduction inhibitor neoadjuvantly in postmenopausal patients with invasive hormone-sensitive breast cancer.


METHODS
Postmenopausal women with hormone-sensitive breast cancer were given three months of letrozole 2.5mg daily and imatinib 400mg twice daily preoperatively. End-points of this study included clinical and pathologic responses, toxicities, and change in [(18)F]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 Three patients were withdrawn after two months of treatment due to hematoma in tumor and toxicity.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 neoadjuvant 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.
Chow
Louis Wing-Cheong
LW
Hung Chao Hong Integrated Centre for Breast Diseases, University of Hong Kong Medical Centre, Pokfulam, Hong Kong. lwcchow@unimed.hk
Yip
Adrian Yun-San
AY
Loo
Wings Tjing-Yung
WT
Toi
Masakazu
M
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D047072:Aromatase Inhibitors; D001549:Benzamides; D001943:Breast Neoplasms / Q000188:drug therapy*; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D000077289:Letrozole; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy; D009570:Nitriles / Q000627:therapeutic use*; D010865:Pilot Projects; D010879:Piperazines / Q000627:therapeutic use*; D017698:Postmenopause; D011743:Pyrimidines / Q000627:therapeutic use*; D015398:Signal Transduction; D014230:Triazoles / Q000627:therapeutic use*
D047072:Aromatase Inhibitors; D001549:Benzamides; D009570:Nitriles; D010879:Piperazines; D011743:Pyrimidines; D014230:Triazoles; D000077289:Letrozole; D000068877:Imatinib Mesylate