Role of Cytochrome P450 Polymorphisms on Breast Cancer Treatment

Abstract

Pharmacogenetics is one of the key factors that is responsible for biological signaling variations that can lead to various diseases. Being led by genetic mutations, breast cancer is affected at higher level due to pharmacogenetic variations. Chemotherapeutic drug is mainly bio transformed in the liver by cytochrome P450 (CYP) enzyme. CY450 isoforms and polymorphisms direct inter individual and interethnic variability in pharmacokinetics and pharmacodynamics of drugs. This further leads to alteration in cancer prognosis. This paper discusses clinically used drugs in breast cancer treatment where interethnic differences in drug safety and efficacy are known to exist. Best known anticancer drug for estrogen receptor-positive breast cancer is Tamoxifen and its efficacy depends predominantly on genetic variants of CYP2D6. Other polymorphisms of CYP3A4, CYP3A5, and sulfotransferase1A1 (SULT1A1) also provide important information about mechanism of tamoxifen activity and resistance. Many chemotherapeutics like anthracyclines have also showed association with polymorphism of genes (CBR3, ABCB1, glutathione-related transporter genes, oxidative stress-related genes) and clinical outcomes. Many chemotherapeutic drug including taxanes, gemcitabine, capecitabine/5-fluorouracil, vinorelbine, methotrexate, and cyclophosphamide are being studies for the association of genetic variations with their bioactivity.