Drug-Metabolizing Enzyme Polymorphisms Predict Clinical Outcome in a Node-Positive Breast Cancer Cohort

Purpose Adjuvant chemotherapy cures only a subset of women with nonmetastatic breast cancer. Genotypes in drug-metabolizing enzymes, including functional polymorphisms in cytochrome P450 (CYP) and glutathione S-transferases (GST), may predict treatment-related outcomes. Patients and Methods We examined CYP3A4*1B, CYP3A5*3, and deletions in GST μ (GSTM1) and θ (GSTT1), as well as a priori–defined combinations of polymorphisms in these genes. Using a cohort of 90 node-positive breast cancer patients who received anthracycline-based adjuvant chemotherapy followed by high-dose multiagent chemotherapy with stem-cell rescue, we estimated the effect of genotype and other known prognostic factors on disease-free survival (DFS) and overall survival (OS). Results Patients who carried homozygous CYP3A4*1B and CYP3A5*3 variants and did not carry homozygous deletions in both GSTM1 and GSTT1 (denoted low-drug genotype group) had a 4.9-fold poorer DFS (P = .021) and a four-fold poorer OS (P = .031) compared with individ...