TY - JOUR
T1 - Pharmacogenomics of breast cancer therapy
T2 - An update
AU - Westbrook, Kelly
AU - Stearns, Vered
N1 - Funding Information:
Conflict of interest: VS received investigator-initiated research funding from Abraxis (Celgene), Merck, Novartis and Pfizer.
Funding Information:
Financial support: Supported in part by Susan G. Komen for the Cure , by P30 CA006973 , and by Grant #5T32CA009071-32, Molecular Targets for Cancer Detection and Treatment.
PY - 2013/7
Y1 - 2013/7
N2 - Clinical and histopathologic characteristics of breast cancer have long played an important role in treatment decision-making. Well-recognized prognostic factors include tumor size, node status, presence or absence of metastases, tumor grade, and hormone receptor expression. High tumor grade, presence of hormone receptors, and HER2-positivity are a few predictive markers of response to chemotherapy, endocrine manipulations, and anti-HER2 agents, respectively. However, there is much heterogeneity of outcomes in patients with similar clinical and pathologic features despite equivalent treatment regimens. Some of the differences in response to specific therapies can be attributed to somatic tumor characteristics, such as degree of estrogen receptor expression and HER2 status. In recent years, there has been great interest in evaluating the role that pharmacogenetics/pharmacogenomics, or variations in germline DNA, play in alteration of drug metabolism and activity, thus leading to disparate outcomes among patients with similar 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.
AB - Clinical and histopathologic characteristics of breast cancer have long played an important role in treatment decision-making. Well-recognized prognostic factors include tumor size, node status, presence or absence of metastases, tumor grade, and hormone receptor expression. High tumor grade, presence of hormone receptors, and HER2-positivity are a few predictive markers of response to chemotherapy, endocrine manipulations, and anti-HER2 agents, respectively. However, there is much heterogeneity of outcomes in patients with similar clinical and pathologic features despite equivalent treatment regimens. Some of the differences in response to specific therapies can be attributed to somatic tumor characteristics, such as degree of estrogen receptor expression and HER2 status. In recent years, there has been great interest in evaluating the role that pharmacogenetics/pharmacogenomics, or variations in germline DNA, play in alteration of drug metabolism and activity, thus leading to disparate outcomes among patients with similar 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.
KW - Aromatase inhibitor
KW - Breast cancer
KW - CYP2D6
KW - Chemotherapy
KW - Endocrine therapy
KW - Pharmacogenetics
KW - Single nucleotide polymorphism
KW - Tamoxifen
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U2 - 10.1016/j.pharmthera.2013.03.001
DO - 10.1016/j.pharmthera.2013.03.001
M3 - Review article
C2 - 23500718
AN - SCOPUS:84877927925
SN - 0163-7258
VL - 139
SP - 1
EP - 11
JO - Pharmacology and Therapeutics
JF - Pharmacology and Therapeutics
IS - 1
ER -