Federica Mazzuca1, Andrea Botticelli1, Eva Mazzotti2, Marco La Torre3, Marina Borro4, Luca Marchetti5, Chiara Maddalena1, Giovanna Gentile4, Maurizio Simmaco4, Paolo Marchetti1. 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, School of Medicine and Psychology, University of Rome La Sapienza, Rome, Italy.
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.
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 cancerpatients treated with AI-based adjuvant therapy and the relationship with the CYP19A1 genotypes. MATERIALS AND METHODS: Forty-five postmenopausal breast cancerpatients (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.
Entities:
Keywords:
Adjuvant hormonal therapy; CYP19A1; aromatase inhibitor; breast cancer; rs4646; single nucleotide polymorphisms
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