Cyclophosphamide-metabolizing enzyme polymorphisms and survival outcomes after adjuvant chemotherapy for node-positive breast cancer: a retrospective cohort study.

Introduction: Cyclophosphamide-based adjuvant chemotherapy is a mainstay of treatment for women with node-positive breast cancer, but is not universally effective in preventing recurrence. Pharmacogenetic variability in drug metabolism is one possible mechanism of treatment failure. We hypothesize that functional single nucleotide polymorphisms (SNPs) in drug metabolizing enzymes (DMEs) that activate (CYPs) or metabolize (GSTs) cyclophosphamide account for some of the observed variability in disease outcomes.

Interleukin-6 -174G-->C polymorphism is associated with improved outcome in high-risk breast cancer.

Axillary lymph node involvement in breast cancer is a marker of recurrence risk. Despite aggressive adjuvant therapy, recurrence in patients with four or more involved lymph nodes approaches 50% at 5 years from diagnosis. Markers that can distinguish those likely to relapse from those likely to be cured are needed to tailor therapy and provide accurate prognostic information to patients.