Limitations in Adjuvant Breast Cancer Therapy: The Predictive Potential of Pharmacogenetics and Pharmacogenomics

Abstract

Adjuvant therapy improves survival in breast cancer patients. However, both antihormonal agents and cytostatic chemotherapy meet with variable success. We have searched the literature for biological causes of variability in drug response. Evidence suggests that additional markers may be introduced because of their potentially predictive value in adjuvant therapy: i) overexpression of epidermal growth factor receptor is likely inversely correlated to the sensitivity to estrogen antagonists; ii) presence of the GAB2 adaptor protein and of the ABCC3 and mdr-1 efflux pumps modulates taxane sensitivity in HER2-positive breast cancer; and iii) CYP2D6 genotyping should be a routine measure to avoid failure of tamox-ifen treatment. In contrast, there is little in the way of genetic evidence for differences in the pharmacokinetics of other antihormonal or cytostatic drugs. Nevertheless, genotypes may affect efficacy and toxicity of cytostatic drugs (e.g. doxorubicin), but this evidence has to be confirmed by prospective trials.