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|Ref Type||Journal Article|
|Authors||Chow LW, Yip AY, Loo WT, Toi M|
|Title||Evaluation of neoadjuvant inhibition of aromatase activity and signal transduction in breast cancer.|
|Date||2008 Apr 18|
|Abstract Text||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.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.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 Three patients were withdrawn after two months of treatment due to hematoma in tumor and toxicity.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.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.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|KIT positive||breast cancer||predicted - sensitive||Imatinib + Letrozole||Phase 0||Actionable||In a pilot trial, Gleevec (imatinib mesylate) and Femara (letrozole) combination treatment resulted in clinical partial response in 90% (9/10) and stable disease in 10% (1/10) of the evaluable patients with invasive hormone-sensitive breast cancer, 8 of the 13 enrolled patients had KIT-positive tumors (PMID: 18248884).||18248884|