ISSN 1308-8734 | E-ISSN 1308-8742
Original Article
CYP19A1 Genetic Polymorphisms rs4646 and Osteoporosis in Patients Treated with Aromatase Inhibitor-Based Adjuvant Therapy
1 Department of Clinical Oncology, Sant’Andrea Hospital, School of Medicine and Psychology, University of Rome La Sapienza, Rome, Italy  
2 Department of Emergency Medicine, Acıbadem University School of Medicine, İstanbul, Turkey  
3 Department of General Surgery, Sant’Andrea Hospital, School of Medicine and Psychology, University of Rome La Sapienza, Rome, Italy  
4 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  
5 Department of Clinical Oncology, Policlinico Umberto I, Faculty of Medicine and Psychology, University of Rome La Sapienza, Rome, Italy  
Eurasian J Med 2016; 48: 10-14
DOI: 10.5152/eurasianjmed.2015.008
Key Words: Adjuvant hormonal therapy, rs4646, aromatase inhibitor, breast cancer, CYP19A1, single nucleotide polymorphisms
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.

 

Materials and 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.

 

Conclusion: 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.

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