Abstract
BackgroundAdjuvant endocrine therapies are known to induce undesirable adverse effects such as vasomotor, vaginal and musculoskeletal symptoms among breast cancer patients. Drugs used in these therapies are often metabolised by cytochrome P450 (CYP) enzymes, in which their metabolising activities can be modified by single nucleotide polymorphisms (SNP) in CYP genes and CYP genotypes. This review aims to explore whether SNPs or genotypes of CYP are associated with the occurrence, frequency and severity of vasomotor, vaginal and musculoskeletal symptoms in breast cancer patients on adjuvant endocrine therapies.MethodsA literature review was conducted using five electronic databases, resulting in the inclusion of 14 eligible studies, and their findings were presented narratively. Selected items from the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist were used for critical appraisal of the reporting quality of the included studies.ResultsMost of the included studies showed that SNPs or genotypes of CYP that modify its metabolising activity have no effect on the occurrence, frequency or severity of vasomotor symptoms, including hot flashes. One study showed no correlation of these genetic variations in CYP with musculoskeletal symptoms, and no data were available on the association between such genetic variations and vaginal symptoms.ConclusionsOverall, genetic variations in CYP have no effect on the experience of hot flashes among breast cancer patients. We recommend exploration of the link between the active metabolites of chemotherapeutic drugs and the molecules shown to affect the occurrence or severity of hot flashes, and the establishment of the relationship between such genetic variations and patients’ experience of musculoskeletal and vaginal symptoms. Subgroup analyses based on patients’ duration of adjuvant endocrine therapies in such studies are recommended.
Highlights
Adjuvant endocrine therapies that involve the use of drugs such as tamoxifen and aromatase inhibitors (AIs), are often administered to breast cancer patients who have completed curative treatments [1]
Overall, genetic variations in cytochrome P450 (CYP) have no effect on the experience of hot flashes among breast cancer patients
Tamoxifen is primarily metabolised by an isoform of CYP named cytochrome P450 2D6 (CYP2D6), which eventually converts tamoxifen into the active metabolite endoxifen, other isoforms including CYP3A4, CYP3A5, CYP2C9, CYP2C19 and CYP2B6 are involved [11, 12]
Summary
Adjuvant endocrine therapies that involve the use of drugs such as tamoxifen and aromatase inhibitors (AIs), are often administered to breast cancer patients who have completed curative treatments [1]. Tamoxifen is primarily metabolised by an isoform of CYP named cytochrome P450 2D6 (CYP2D6), which eventually converts tamoxifen into the active metabolite endoxifen, other isoforms including CYP3A4, CYP3A5, CYP2C9, CYP2C19 and CYP2B6 are involved [11, 12] Another CYP isoform, CYP19A1 which codes for aromatase, an enzyme involved in oestrogen synthesis, was suggested to counteract the effects of AIs [13], which are drugs that increase the risk of vasomotor symptoms such as hot flashes. Adjuvant endocrine therapies are known to induce undesirable adverse effects such as vasomotor, vaginal and musculoskeletal symptoms among breast cancer patients Drugs used in these therapies are often metabolised by cytochrome P450 (CYP) enzymes, in which their metabolising activities can be modified by single nucleotide polymorphisms (SNP) in CYP genes and CYP genotypes. This review aims to explore whether SNPs or genotypes of CYP are associated with the occurrence, frequency and severity of vasomotor, vaginal and musculoskeletal symptoms in breast cancer patients on adjuvant endocrine therapies
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