title: The influence of genetic polymorphisms on the efficacy and side effects of anastrozole in postmenopausal breast cancer patients.
abstract: Breast cancer is a common cause of cancer mortality among women. Several genetic factors have been implicated in its development. Current treatment guidelines for estrogen receptor-positive breast cancer recommend that anastrozole [or any of the other two aromatase inhibitors (letrozole and exemestane)] is used as an alternative to tamoxifen or following several years of tamoxifen treatment. Nevertheless, this approach is still associated with many challenges, ranging from the recurrence of breast cancer to considerable interindividual variability in the tolerability of anastrozole, which may cause adverse effects, such as musculoskeletal symptoms, and lead to the withdrawal of many patients from treatment. Variabilities in the genes encoding the drug target (aromatase) or its metabolizing enzymes (CYP3A and UGT1A) contribute toward the interindividual variability in anastrozole's pharmacokinetics and/or pharmacodynamics. This paper reviews the role of genetic polymorphisms of CYP19A1, CYP3A4, and UGT1A4 in the responses of female hormone receptor-positive postmenopausal breast cancer patients to anastrozole. Many reviews in the literature have suggested that the study of functional polymorphisms and investigation of relevant genetic markers may provide valuable information in predicting responses to anastrozole in terms of its therapeutic and adverse effects. Nevertheless, more studies are required before the knowledge of its pharmacogenomics can be applied to the individualization of treatment to ensure that patients receive the maximum benefits. Therefore, future analyses, including but not limited to genome-wide association studies, are encouraged to address some of the gray areas in the pharmacogenomics of anastrozole therapy in postmenopausal breast cancer cases; this will help in providing guidance for future pharmacogenomics protocols when anastrozole is utilized in patients' management.
authors.affiliation: aHuman Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia bDepartment of Physiology, College of Health Sciences, Usmanu Dan Fodiyo University, Sokoto, Nigeria.
authors.forename: Murtala B
authors.initials: MB
authors.lastname: Abubakar
authors.forename: Keat
authors.initials: K
authors.lastname: Wei
authors.forename: Siew Hua
authors.initials: SH
authors.lastname: Gan
mesh_terms: D000077384:Anastrozole; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000493:pharmacokinetics*; D001141:Aromatase / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D005260:Female; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D009570:Nitriles / Q000009:adverse effects / Q000493:pharmacokinetics*; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause; D057285:Precision Medicine; D014230:Triazoles / Q000009:adverse effects / Q000493:pharmacokinetics*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D009570:Nitriles; D014230:Triazoles; C019787:bilirubin glucuronoside glucuronosyltransferase; D000077384:Anastrozole; D001141:Aromatase; C561410:CYP19A1 protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D014453:Glucuronosyltransferase