title: CYP2D6*4 polymorphism: A new marker of response to hormonotherapy in male breast cancer?
abstract: BACKGROUND
  Tamoxifen remains the standard hormonotherapy for Male breast cancer patients (MBC). Previous studies, in women, tried to evaluate the impact of CYP2D6 polymorphisms in tamoxifen efficacy with conflicting results. Herein we analyze the relation between CYP2D6*4 polymorphism and survival in MBC patients.
  
  
  METHODS
  Fifty-three patients, proposed to tamoxifen in adjuvant setting, were enrolled. Clinical information was collected from records and histological revision with additional immunochemistry analysis was done to better characterize the tumors. Comprehensive CYP2D6*4 genotyping from blood or tumor tissue was performed and translated into two predicted metabolic activity groups.
  
  
  RESULTS
  Patients included in the two CYP2D6*4 groups did not differ concerning to age, histological characteristics, and primary treatments performed. Median age at diagnosis was 63 years-old and patients were submitted at least to mastectomy and adjuvant hormonotherapy. Recurrence was observed in 7 patients (13.2%) and 13 patients (25.5%) died with a 5-year disease-free survival of 86.2%. The poorer metabolizer group had a high risk for recurrence (p = 0.034) and this outcome effect remains in different subgroups: in tumors larger than 2 cm (p < 0.001), nodal status, N0 vs N+ (p = 0.04) and in advanced stage, stage III (p < 0.001). Poorer metabolizer patients had also a worse overall survival when tumors were larger than 2 cm (p = 0.03).
  
  
  CONCLUSIONS
  In our series, there was an association between CYP2D6*4 polymorphism and a probability of recurrence, with a consistent effect in risk groups defined by classic prognostic factors. Multicentric studies with larger samples are needed to validate these results.
authors.affiliation: Department of Medical Oncology, Portuguese Institute of Oncology of Porto, António Bernardino de Almeida Street, 4200-072 Porto, Portugal. Electronic address: p_abreu@sapo.pt.
authors.forename: M H
authors.initials: MH
authors.lastname: Abreu
authors.affiliation: Molecular Oncology Group, Portuguese Institute of Oncology of Porto, António Bernardino de Almeida Street, 4200-072 Porto, Portugal.
authors.forename: M
authors.initials: M
authors.lastname: Gomes
authors.affiliation: Department of Pathology, Portuguese Institute of Oncology of Porto, António Bernardino de Almeida Street, 4200-072 Porto, Portugal.
authors.forename: F
authors.initials: F
authors.lastname: Menezes
authors.affiliation: Department of Medical Oncology, Portuguese Institute of Oncology of Porto, António Bernardino de Almeida Street, 4200-072 Porto, Portugal.
authors.forename: N
authors.initials: N
authors.lastname: Afonso
authors.affiliation: dCISUC, Department of Informatics Engineering, Faculty of Sciences and Technology, University of Coimbra, Polo II, Pinhal de Marrocos, 3030-788 Coimbra, Portugal.
authors.forename: P H
authors.initials: PH
authors.lastname: Abreu
authors.affiliation: Molecular Oncology Group, Portuguese Institute of Oncology of Porto, António Bernardino de Almeida Street, 4200-072 Porto, Portugal.
authors.forename: R
authors.initials: R
authors.lastname: Medeiros
authors.affiliation: Department of Medical Oncology, Portuguese Institute of Oncology of Porto, António Bernardino de Almeida Street, 4200-072 Porto, Portugal.
authors.forename: D
authors.initials: D
authors.lastname: Pereira
authors.affiliation: Department of Pathology and Molecular Immunology, Biomedical Sciences Institute of Abel Salazar, University of Porto, Jorge Viterbo Ferreira Street, n.° 228, 4050-313 Porto, Portugal.
authors.forename: C
authors.initials: C
authors.lastname: Lopes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D018567:Breast Neoplasms, Male / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics / Q000378:metabolism*; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008297:Male; D008408:Mastectomy; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000235:genetics; D009367:Neoplasm Staging; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D016019:Survival Analysis; D013629:Tamoxifen / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D005819:Genetic Markers; D013629:Tamoxifen; D019389:Cytochrome P-450 CYP2D6
keywords: CYP2D6*4 polymorphism; Disease-free survival; Male breast cancer; Overall-survival; Tamoxifen