Pharmacogenomics in breast cancer: current trends and future directions

Abstract

Pharmacogenomics is the study of genetic variations between individuals to predict the risk of toxic side effects and the probability that a patient will respond to single- or multidrug chemotherapy. Breast cancer remains one of the most common cancers among women worldwide and is second only to lung cancer in cancerrelated death. A better understanding of the mechanisms of initiation and progression of breast cancer is needed for early diagnosis and development of better therapeutic methodologies. Differences in cancer patients' responses to chemotherapy have often been attributed to pathogenesis and severity of the disease, drug interactions, patient's age, gender, nutritional status, organ functions and tumor biology. It is now well recognized that genetic variations in drug target genes, disease pathway genes and drug metabolizing enzymes can have greater influence on drug efficacy and toxicity. In addition, germline variants can be used to study breast cancer susceptibility, as well as the variable response to both drug and radiation therapy used in the treatment of breast cancer. This review discusses clinically relevant individual gene variations that influence breast cancer susceptibility and cancer therapy, as well as the microarray-based expression profiling studies that have great potential in cancer pharmacogenomics in terms of tumor classification, drug and biomarker discovery and drug efficacy testing.