Gene Expression Profiles in Predicting Chemotherapy Response in Breast Cancer
We hypothesize that changes in tumor gene expression profiles vary in response to different sequences and types of chemotherapy, and that gene expression changes will correlate with tumor response. We are also looking to correlate drug pharmacokinetics and treatment toxicity with genotype of drug metabolizing enzymes and tranporters.Patients with metastatic breast cancer and who have measurable primary breast tumor will be randomized to one of two alternating sequences of adriamycin and docetaxel. Serial tumor biopsies and plasma samples will be obtained for gene expression and proteomic studies to identify biomarkers that will predict for chemotherapy response.
|Study Design:||Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Gene Expression Profiles of Breast Cancer Treated With Sequential Adriamycin and Docetaxel in Relation to Tumor Responses|
- 1. Evaluate the impact of adriamycin and docetaxel on tumor gene expression profiles.
- 2. Correlate overall tumor response with tumor gene expression profiles.
- To correlate adriamycin and docetaxel pharmacokinetics with:
- 1. Genetic polymorphisms of MDR-1, Cyp3A and GSTs.
- 2. Drug toxicity and tumor response.
|Study Start Date:||April 2002|
Significant inter-individual variation exists in tumor response and chemotherapy toxicity because of unique tumor and patient factors. Individual drugs with distinct mechanisms of action may induce specific genomic and proteomic changes that may be used as predictor for response. We plan to study serial genomic and proteomic profiles in primary breast tumor treated with one of two sequences of alternating adriamycin (A) and docetaxel (T), A>T>A>T>A>T, or T>A>T>A>T>A, at 75mg/m2 3 weekly for each drug. Pharmacokinetic analysis of both drugs will be performed; amplified tumor RNA will be hybridized on Affymetrix® HG-U133+2 array; tumor proteins will be fractionated and profiled with ProteinChip® Array SELDI MS (Ciphergen). Tumor gene expression and proteomic changes will be correlated with treatment response to identify biomarkers that may predict chemotherapy sensitivity.