title: CYP19A1 Genetic Polymorphisms rs4646 and Osteoporosis in Patients Treated with Aromatase Inhibitor-Based Adjuvant Therapy.
abstract: OBJECTIVE
  Third-generation aromatase inhibitors (AI) are potent suppressors of aromatase activity. The aim of this study was to measure the incidence of adverse effects in breast cancer patients treated with AI-based adjuvant therapy and the relationship with the CYP19A1 genotypes.
  
  
  METHODS
  Forty-five postmenopausal breast cancer patients (46-85 yrs) in AI adjuvant treatment were genotyped for the rs4646 polymorphisms of CYP19A1 gene and three variations were identified. Toxicities were registered at each follow-up medical examination, and classified in accord with the Common Terminology Criteria for Adverse Events.
  
  
  RESULTS
  Twenty-four (53.3%) patients presented the GG genotype; 19 (42.2%) the GT, and 2 (4.4%) the TT. The AI treatment was Anastrazole for 35 patients (77.8%) and Letrozole for the others (n=10; 22.2%). Osteoporosis was significantly associated with the GG genotype (p=0.001). Treatment discontinuation (TD) was observed in 6 cases (13.3%). The only parameter able to predict TD was the appearance of severe arthralgia/myalgia (Odds Ratio, OR=23.75; p=0.009), when adjusted for age and AI treatment.
  
  
  CONCLUSIONS
  Our results suggest that CYP19A1 polymorphic variants may influence susceptibility to develop AI-related side effects. Further prospective studies are needed to confirm the role of the aromatase gene (CYP19A1) polymorphisms in predicting adverse effects to AI-based therapy.
authors.affiliation: Department of Clinical Oncology, Sant'Andrea Hospital, School of Medicine and Psychology, University of Rome La Sapienza, Rome, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Mazzuca
authors.affiliation: Department of Clinical Oncology, Sant'Andrea Hospital, School of Medicine and Psychology, University of Rome La Sapienza, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Botticelli
authors.affiliation: Department of Emergency Medicine, Acıbadem University School of Medicine, İstanbul, Turkey.
authors.forename: Eva
authors.initials: E
authors.lastname: Mazzotti
authors.affiliation: Department of General Surgery, Sant'Andrea Hospital, School of Medicine and Psychology, University of Rome La Sapienza, Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: La Torre
authors.affiliation: Department of Advanced Molecular Diagnosis Unit (DiMA), Sant'Andrea Hospital Department of Medical-Surgical Sciences and Translational Medicine, Faculty of Medicine and Psychology, University of Rome La Sapienza, Rome, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Borro
authors.affiliation: Department of Clinical Oncology, Policlinico Umberto I, School of Medicine and Psychology, University of Rome La Sapienza, Rome, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Marchetti
authors.affiliation: Department of Clinical Oncology, Sant'Andrea Hospital, School of Medicine and Psychology, University of Rome La Sapienza, Rome, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Maddalena
authors.affiliation: Department of Advanced Molecular Diagnosis Unit (DiMA), Sant'Andrea Hospital Department of Medical-Surgical Sciences and Translational Medicine, Faculty of Medicine and Psychology, University of Rome La Sapienza, Rome, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Gentile
authors.affiliation: Department of Advanced Molecular Diagnosis Unit (DiMA), Sant'Andrea Hospital Department of Medical-Surgical Sciences and Translational Medicine, Faculty of Medicine and Psychology, University of Rome La Sapienza, Rome, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Simmaco
authors.affiliation: Department of Clinical Oncology, Sant'Andrea Hospital, School of Medicine and Psychology, University of Rome La Sapienza, Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Marchetti
keywords: Adjuvant hormonal therapy; CYP19A1; aromatase inhibitor; breast cancer; rs4646; single nucleotide polymorphisms