title: Impact of CYP2D6 polymorphisms in tamoxifen adjuvant breast cancer treatment.
abstract: The aim of this study is to evaluate the impact of CYP2D6 genotyping in predicting disease-free survival and toxicity in breast cancer patients treated with adjuvant tamoxifen. DNA from 91 patients was genotyped using the AmpliChip CYP450 GeneChip, Roche that facilitates the classification of individuals by testing 27 alleles. When patients were grouped into group 1 (*4/*4, *4/*41, *1/*5 and *2/*5) and group 2 (the remaining genotypes), a significant difference in disease-free survival (DFS) was observed between groups (P = 0.016). The mean DFS in group 1 was 95 months in contrast with 119 months in group 2. No significant relationship was found between the CYP2D6 genotype classification and severe, mild or no toxicity (P = 0.2). Nevertheless, severe, and mild toxicity was more frequent among poor metabolizer patients than in patients with a normal metabolizer pattern (18.8 and 43.8% vs. 10.7 and 36%, respectively). In breast cancer, patients treated with adjuvant tamoxifen, non-functional and severely impaired CYP2D6 variants are associated with a worse DFS and with a higher frequency of severe and mild toxicities. Larger studies of the CYP2D6 genotype-clinical outcomes association are needed to complement initial results.
authors.affiliation: Servicio de Oncología Médica, Hospital de la Santa Creu i Sant Pau, Universitat Autónoma de Barcelona, Barcelona, Spain.
authors.forename: T
authors.initials: T
authors.lastname: Ramón y Cajal
authors.forename: A
authors.initials: A
authors.lastname: Altés
authors.forename: L
authors.initials: L
authors.lastname: Paré
authors.forename: E
authors.initials: E
authors.lastname: del Rio
authors.forename: C
authors.initials: C
authors.lastname: Alonso
authors.forename: A
authors.initials: A
authors.lastname: Barnadas
authors.forename: M
authors.initials: M
authors.lastname: Baiget
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000208:ethnology; D017024:Chemotherapy, Adjuvant / Q000379:methods*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010597:Pharmacogenetics / Q000379:methods*; D012189:Retrospective Studies; D013629:Tamoxifen / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D013629:Tamoxifen; D019389:Cytochrome P-450 CYP2D6