Are pharmacogenomic biomarkers an effective tool to predict taxane toxicity and outcome in breast cancer patients? Literature review

Purpose Breast cancer is a heterogeneous disease, char- acterized by various molecular phenotypes that correlate with different prognosis and response to treatments. Taxa- nes are some of the most active chemotherapeutic agents for breast cancer; however, their utilization is limited, due to hematologic and cumulative neurotoxicity on treated patients. To understand why only some patients experi- ence severe adverse effects and why patients respond and develop resistance with different rates to taxane therapy, the metabolic pathways of these drugs should be completely unraveled. The variant forms of several genes, related to taxane pharmacokinetics, can be indicative markers of clin- ical parameters, such as toxicity or outcome. Methods The search of the data has been conducted through PubMed database, presenting clinical data, clinical trials and basic research restricted to English language until June 2015. Results We studied the literature in order to find any pos- sible association between the major pharmacogenomic variants and specific taxane-related toxicity and patient outcome. We found that the data of these studies are * Susanna Scarpa susanna.scarpa@uniroma1.it Francesca De Iuliis francesca.deiuliis@yahoo.it Gerardo Salerno sagerardo@libero.it Ludovica Taglieri ludovica.taglieri@yahoo.it 1 Experimental Medicine Department, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy sometimes discordant, due to both the small number of enrolled patients and the heterogeneity of the examined population. Conclusions Among all analyzed genes, only CYP1B1 and ABCB1 resulted the strongest candidates to become biomarkers of clinical response to taxane therapy in breast cancer, although their utilization still remains an experi- mental procedure. In the future, greater studies on genetic polymorphisms should be performed in order to identify differentiating signatures for patients with higher toxic- ity and with resistant or responsive outcome, before the administration of taxanes.