Histopathologic and clinical features of breasts cancers possess lengthy played a

Histopathologic and clinical features of breasts cancers possess lengthy played a significant part in treatment decision-making. similar medical and pathologic features despite comparable treatment regimens. A number of the difference in response to particular therapies could be related to somatic tumor features such as amount of estrogen receptor manifestation and HER2 position. Lately there’s been great fascination with evaluating the part that pharmacogenetics/pharmacogenomics or variants in germline DNA play in alteration of medication rate of metabolism and activity therefore leading to disparate outcomes among patients with similar BP897 tumor characteristics. The utility of these variations in treatment decision-making remains debated. Here we review the data available to date on genomic variants that may influence response to drugs commonly used to treat breast cancer. While none of the variants reported to date have demonstrated clinical utility ongoing prospective studies and increasing understanding of pharmacogenetics will allow us to better predict risk of toxicity or likelihood of response to specific treatments and to provide a more personalized therapy. Introduction Breast cancer continues to be the leading malignancy diagnosed in women in Western societies. It is estimated that 226 870 women will be diagnosed with and 39 510 women will die of breast cancer in the United States in 2012 (National Cancer Institute 2012 Treatment for breast cancer BP897 is constantly evolving as new technologies agents and strategies are discovered. Advances in the early detection and adjuvant treatment of breast cancer have already led to a significant reduction in disease-related relapse and death (Berry et al. 2005 Early Breast Cancer Trialists’ Collaborative 2012 However there is significant variation in drug response and survival outcomes in individuals treated with equivalent regimens including hormonal agents cytotoxic agents and novel targeted therapies. Traditionally clinical and histopathologic factors alone have been used to guide choice of therapy. These factors include tumor stage tumor size nodal status and intra-tumoral characteristics such as grade expression of estrogen and progesterone receptors and HER2 status. These factors may be prognostic indicating the aggressiveness of a tumor and likelihood of relapse without systemic therapy predictive of response to specific treatments or both. In recent years advances in technology such as the sequencing of the human genome development of high-throughput DNA analysis and popularization of the idea of “personalized medicine” have led to a significant interest in how differences in genetic makeup may be used to predict treatment safety and efficacy. In the last decade there has been an increase in the number of studies investigating the role of pharmacogenetics in the treatment of breast and other cancers. The term pharmacogenetics (here used synonymously with pharmacogenomics) refers to the study of the influence of a patient’s genetic makeup on their response to drug therapy including toxicity and efficacy. Technologic advances have allowed the rapid assessment of gene expression and function. This includes assessment of both tumor (somatic) and BP897 host (germline) genetic variation. Tissue microarrays for example permit the evaluation of expression patterns of thousands of tumor genes which have proven critical in providing prognostic and predictive information regarding specific biologic subsets of cancer. Genetic variations may be in the form of DNA alterations including nucleotide repeats insertions deletions or substitutions. The alteration of one nucleotide a single nucleotide polymorphism (SNP) can lead to absence or altered enzyme activity and thus to a significant impact on the disposition of and/or response to a drug. These alterations may affect drug toxicity and efficacy in a variety of ways. Changes in the coding region of DNA may result in amino acid substitutions in the translated protein and changes in the noncoding regions of DNA can alter different aspects of protein Akt2 function compared to a wild type protein. The goal of BP897 pharmacogenomic studies is to identify genetic alterations such as BP897 SNPs that considerably affect the function or expression of proteins involved in the pharmacokinetics or pharmacodynamics of therapeutic drugs. The ultimate goal of selecting a particular drug for a patient based on their genetic makeup is to improve efficacy and safety. To date.