title: Are pharmacogenomic biomarkers an effective tool to predict taxane toxicity and outcome in breast cancer patients? Literature review.
abstract: OBJECTIVE
  Breast cancer is a heterogeneous disease, characterized by various molecular phenotypes that correlate with different prognosis and response to treatments. Taxanes 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 experience 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 clinical 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 possible association between the major pharmacogenomic variants and specific taxane-related toxicity and patient outcome. We found that the data of these studies are 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 experimental procedure. In the future, greater studies on genetic polymorphisms should be performed in order to identify differentiating signatures for patients with higher toxicity and with resistant or responsive outcome, before the administration of taxanes.
authors.affiliation: Experimental Medicine Department, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy. francesca.deiuliis@yahoo.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: De Iuliis
authors.affiliation: Experimental Medicine Department, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy. sagerardo@libero.it.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Salerno
authors.affiliation: Experimental Medicine Department, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy. ludovica.taglieri@yahoo.it.
authors.forename: Ludovica
authors.initials: L
authors.lastname: Taglieri
authors.affiliation: Experimental Medicine Department, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy. susanna.scarpa@uniroma1.it.
authors.forename: Susanna
authors.initials: S
authors.lastname: Scarpa
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D001952:Bridged-Ring Compounds / Q000009:adverse effects* / Q000627:therapeutic use; D065633:Cytochrome P-450 CYP1B1 / Q000235:genetics* / Q000378:metabolism; D019317:Evidence-Based Medicine; D005260:Female; D006801:Humans; D010597:Pharmacogenetics / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D043823:Taxoids / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents; D015415:Biomarkers; D001952:Bridged-Ring Compounds; D043823:Taxoids; C080625:taxane; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1
keywords: ABCB1; CYP1B1; Pharmacogenomics; Polymorphism; SNP; Taxane