CORRELATION OF CYP2D6’S GENOTYPE AND PHENOTYPE WITH CLINICOPATHOLOGICAL CHARACTERIZATION AND IMPACT ON SURVIVAL IN BRAZILIAN BREAST CANCER POPULATION: A PROSPECTIVE STUDY.

Thais Abreu de ALMEIDA1, Jeanine Marie NARDIN1, Angela DASENBROCK1, Elisa GAIO1, Raquel SKRSYPCSAK1, Lucia de NORONHA2, Hiltrud BRAUCH3, José Claudio CASALI DA ROCHA1

Hospital Erasto Gaertner – Liga Paranaense de Combate ao CâncerObjectives:Breast cancer has a broad spectrum of clinicopathological and molecular presentations that can be influenced by genetics, epigenetics, and risk factors. It determines a huge variability of treatment outcomes, which support a tailor-made tumor analysis for better choice therapy. CYP enzymes (cytochrome P450s) metabolize carcinogens, drugs and hormones. P450(CYP)2D6 can be risk modifier factors since it is highly polymorphic and presents with variable functional activities. The main objective of this study was to prospectively evaluate the correlation of CYP2D6 genotype, phenotype, clinicopathological profile, and survival, in Brazilian breast cancer population.Methodology:Prospectively, 363 subjects with breast cancer were recruited, clinicopathological data were registered, and blood sample was collected at first visit. CYP2D6 genotyping was performed in 188 subjects for 9 alleles using MALDI-TOF and Taqman. For genotype interpretation, CYP2D6 activity score was applied to predict phenotypes: absent (PM), reduced (IM), normal (EM), and increased (UM) enzyme function. Genotypes did not deviate from Hardy-Weinberg equilibrium. Kaplan-Meier plot for overall survival were used for each comparison (log-rank test). All significance levels were set as <0.05.Results:After a median follow-up of 27 months, 363 subjects were recruited with 38% premenopausal, 43.8% stage IIA/IIB, 42.1% neoadjuvant chemotherapy, 71.1% estrogen receptor positive and 18.1% HER2 positive. From 188 patients, 50% were EM or UM. CYP2D6 phenotypes did not influenced prognostic factors: hormonal receptor status (p=0.122) and staging. Overall survival and disease-free survival was 96.9% and 96.3% at 12 months, respectively. No difference in overall survival was observed among phenotypes PM/IM and EM (HR 1.26, IC95% 0.27 a 5.86, p=0.764) either in disease-free survival (p=0.999).Conclusion:There was no association between CYP2D6 phenotypes and clinicopathological characteristics and them did not influenced overall and disease-free survival. Further follow-up data will analyze this cohort at 50 months and in a subset of estrogen receptor positive group.Breast cancer; Brazil; CYP2D6; Prospective Study