Abstract
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. 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. 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. 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.
Highlights
Third-generation aromatase inhibitors are potent suppressors of aromatase activity and represent the standard care for adjuvant therapy in postmenopausal patients with hormonal receptors-positive breast cancer [1, 2].Aromatase is the enzyme that catalyses the peripheral conversion of androstenedione and testosterone to oestrone (E1) and estradiol (E2)
The only parameter able to predict Treatment discontinuation (TD) was the appearance of severe arthralgia/myalgia (Odds Ratio, OR=23.75; p=0.009), when adjusted for age and aromatase inhibitors (AI) treatment
Our results suggest that CYP19A1 polymorphic variants may influence susceptibility to develop AI-related side effects
Summary
Third-generation aromatase inhibitors (letrozole, anastrozole and exemestane) are potent suppressors of aromatase activity and represent the standard care for adjuvant therapy in postmenopausal patients with hormonal receptors-positive breast cancer [1, 2].Aromatase is the enzyme that catalyses the peripheral conversion of androstenedione and testosterone to oestrone (E1) and estradiol (E2). In women with ovarian failure, this process may represent the main source of oestrogen production. The inhibition of this pathway causes a profound oestrogen deficiency and low levels of oestrogen may affect many organs, including the brain, the skeleton and the skin as well as the cardiovascular and genitourinary systems [3]. Aromatase inhibitors’ adverse effects are similar to menopause-related symptoms. They cause the interruption of adjuvant treatment in 20-30% of the cases. Oestrogens have a regulatory effect on bone metabolism by stimulating bone growth and inhibiting bone resorption, so their depletion leads to bone loss that causes a progressive osteopenic and/or osteoporotic status and a higher risk of fractures [3]
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