Variability of DNA Repair and Oxidative Stress Genes Associated with Worst Pain in Breast Cancer Survivors on Aromatase Inhibitors
Ontology highlight
ABSTRACT:
SUBMITTER: Wagner M
PROVIDER: S-EPMC10671149 | biostudies-literature | 2023 Oct
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The role of the general internist in the care of breast cancer survivors is increasing as the number of women living with breast cancer continues to rise. Most breast cancers occurring in women older than 50 years are estrogen receptor- and/or progesterone receptor-positive, and adjuvant endocrine therapy plays an important role in the treatment plan. Aromatase inhibitors are becoming the preferred endocrine therapy, and general internists caring for breast cancer survivors need to be familiar with their use and adverse effect profile. This article reviews the use of aromatase inhibitors, the frequency of common adverse effects, and strategies for their management.
| S-EPMC2878260 | biostudies-literature
Project description:PURPOSE:Aromatase inhibitors (AIs) are a potentially life-saving treatment for breast cancer survivors, yet poor adherence to treatment is a prevalent problem. A common adverse effect of AI treatment is arthralgia, which is identified by survivors as a major reason for treatment discontinuation. Women who experience arthralgia on AIs often report feeling they have aged rapidly while on the treatment. In the present study, we examined whether arthralgia-associated ageing perceptions predicted non-adherence. PATIENTS AND METHODS:We conducted a prospective cohort study among women with stage I-III breast cancer, who were on an AI and completed the Penn Arthralgia Aging Scale within 2 years of AI initiation. Adherence data were abstracted from medical charts by trained raters. Cox proportional hazard analysis was used to determine the relationship between ageing perceptions and time to non-adherence. All analyses included adjustments for joint pain severity. RESULTS:Among 509 participants, 144 (28.3%) were non-adherent. As hypothesised, women with high levels of ageing perceptions were at greater risk of non-adherence than women with low levels of ageing perceptions (adjusted hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.10-2.67; p = .02). High levels of depressive symptoms were also uniquely associated with increased risk of non-adherence (adjusted HR, 1.63; 95% CI, 1.03-2.59; p = .04). CONCLUSION:Perceptions of ageing related to arthralgia and depressive symptoms predicted non-adherence to AIs. These findings suggest that interventions that address negative beliefs about ageing due to AI-related arthralgia and depressive mood can potentially improve rates of adherence to AIs.
| S-EPMC5803454 | biostudies-other
Project description:The use of aromatase inhibitors (AIs) is associated with higher rates of cardiovascular events and lower endothelial function in breast cancer survivors. Psychosocial stress is associated with higher levels of inflammatory and aging markers, and lower endothelial function in otherwise healthy subjects. These associations among breast cancer survivors on AIs are not well defined. A cross-sectional study of 30 breast cancer survivors on AIs was performed to assess the associations between self-reported scores of psychosocial measures of depression, anxiety, and stress assessed by validated questionnaires with markers of inflammation (CRP; IL-6; IL-18), aging (p16INK4a), and endothelial function (ICAM-1, EndoPAT ratio). Significant positive correlations were observed between psychosocial measures and inflammatory markers including CRP, IL-6, and ICAM-1. However, no psychosocial scores were related to endothelial function or gene expression of the aging biomarker p16INK4a. Overall, survivors had endothelial dysfunction with reduced EndoPAT ratios. Psychosocial stress is associated with greater inflammation in breast cancer survivors on AIs, corroborating previous studies in cancer-free populations. The lack of association between psychosocial stress and either endothelial function or aging biomarkers could be due to the already low endothelial function and accelerated aging in our cohort of breast cancer survivors on AIs, though our small sample size limits conclusions. Further work in a larger and more diverse cohort of patients is needed to further understand the relationships among inflammation, aging and endothelial function in breast cancer survivors.
| S-EPMC9886974 | biostudies-literature
Project description:BackgroundAromatase inhibitor (AI)-induced joint pain is a common toxicity of AI treatment. Although many studies have been conducted to examine the occurrence and severity of AI-induced joint pain in breast cancer survivors, none of the studies focused on the Chinese population with breast cancer. Given that the differences in cultural background and the genetic structure between Asians and Caucasians may contribute to different phenotypes of joint pain, this cross-sectional study was therefore conducted to examine the prevalence of AI-induced joint pain among Chinese breast cancer survivors receiving AI treatment and the correlates of pain.MethodsThis cross-sectional study was conducted in a tertiary hospital in China. Breast cancer survivors undergoing AI treatment were recruited to complete the following questionnaires: a self-designed baseline data form, the Nordic Musculoskeletal Questionnaire (NMQ), the Brief Pain Inventory (BPI), the 36-Item Short Form Health Survey (SF-36), and the Functional Assessment of Cancer Therapy-Breast (FACT-B). Based on the assessment results of NMQ (if the participant indicated pain in specific body parts), participants were then invited to complete other questionnaires to specifically assess the joint symptoms, including the Oxford Knee Score (OKS), the Oxford Hip Score (OHS), the Michigan Hand Outcomes Questionnaire (MHQ), and the Manchester Foot Pain Disability Questionnaire (MFPDQ). Descriptive analysis was used to analyse participants' baseline data and the prevalence of pain. Stepwise multiple regression was used to identify the correlates of pain.ResultsFour hundred and ten participants were analysed. According to the NMQ, 71.7% of the participants experienced joint symptoms in at least one joint, and the most frequently mentioned joint was knee (39.0%). The diagram in BPI indicated that 28.0% of the participants had the worst pain around knees. In patients with knee pain, the mean OKS score was 40.46 ± 6.19. The sub-scores of BPI for pain intensity and pain interference were 1.30 ± 1.63 and 1.24 ± 1.79, respectively. Patients' poorer physical well-being/functioning, previous use of AI treatment, presence of osteoarthritis, and receiving of physiotherapy were identified as four common correlates of greater severity of pain and pain interference (p < 0.05).ConclusionsChinese breast cancer survivors can experience joint pain at various locations, particularly knees. In addition to increasing the use of interventions for pain alleviation, a comprehensive assessment of survivors' conditions such as physical functioning, history of AI treatment, and presence of osteoarthritis should be emphasized to identify survivors who need more attention and tailored interventions.
| S-EPMC9633515 | biostudies-literature
Project description:ObjectiveThis study examined the effect of 12 months of aerobic and resistance exercise versus usual care on changes in body composition in postmenopausal breast cancer survivors taking aromatase inhibitors (AIs).MethodsThe Hormones and Physical Exercise study enrolled 121 breast cancer survivors and randomized them to either supervised twice-weekly resistance exercise training and 150 min/wk of aerobic exercise (N = 61) or a usual care (N = 60) group. Dual-energy X-ray absorptiometry scans were conducted at baseline, 6 months, and 12 months to assess changes in body mass index, percent body fat, lean body mass, and bone mineral density.ResultsAt 12 months, the exercise group relative to the usual care group had a significant increase in lean body mass (0.32 vs. -0.88 kg, P = 0.03), a decrease in percent body fat (-1.4% vs. 0.48%, P = 0.03), and a decrease in body mass index (-0.73 vs. 0.17 kg/m2 , P = 0.03). Change in bone mineral density was not significantly different between groups at 12 months (0.001 vs. -0.006 g/cm2 , P = 0.37).ConclusionsA combined resistance and aerobic exercise intervention improved body composition in breast cancer survivors taking AIs. Exercise interventions may help to mitigate the negative side effects of AIs and improve health outcomes in breast cancer survivors.
| S-EPMC5450163 | biostudies-literature
Project description:The use of dietary supplements is common in the general population and even more prevalent among cancer survivors. The World Cancer Research Fund/American Institute for Cancer Research specifies that dietary supplements should not be used for cancer prevention. Several dietary supplements have potential pharmacokinetic and pharmacodynamic interactions that may change their clinical efficacy or potentiate adverse effects of the adjuvant endocrine therapy prescribed for breast cancer treatment. This analysis examined the prevalence of self-reported dietary supplement use and the potential interactions with tamoxifen and aromatase inhibitors (AIs) among breast cancer survivors enrolled in three randomized controlled trials of lifestyle interventions conducted between 2010 and 2017. The potential interactions with tamoxifen and AIs were identified using the Natural Medicine Database. Among 475 breast cancer survivors (2.9 (mean) or 2.5 (standard deviation) years from diagnosis), 393 (83%) reported using dietary supplements. A total of 108 different types of dietary supplements were reported and 36 potential adverse interactions with tamoxifen or AIs were identified. Among the 353 women taking tamoxifen or AIs, 38% were taking dietary supplements with a potential risk of interactions. We observed a high prevalence of dietary supplement use among breast cancer survivors and the potential for adverse interactions between the prescribed endocrine therapy and dietary supplements was common.
| S-EPMC8621720 | biostudies-literature
Project description:PurposeThe purpose of this exploratory candidate gene association study was to examine relationships between polymorphisms in oxidative stress and DNA repair genes and pre-adjuvant therapy cognitive function (CF) in postmenopausal women diagnosed with early stage-breast cancer.MethodsUsing a neuropsychological test battery, CF was assessed in 138 women diagnosed with breast cancer prior to initiation of adjuvant therapy and 81 age- and education-matched controls and summarized across eight composites. Participants were genotyped for 39 functional or tagging single nucleotide polymorphisms (SNPs) of select oxidative stress (CAT, GPX1, SEPP1, SOD1, and SOD2) and DNA repair (ERCC2, ERCC3, ERCC5, and PARP1) genes. Multiple linear regression was used to determine if the presence or absence of one or more minor alleles account for variability in CF composite scores. Based on regression findings from the analysis of individual SNPs, weighted multi-gene, multi-polymorphism genetic risk scores (GRSs) were calculated to evaluate the collective effect of possession of multiple protective and/or risk alleles.ResultsEach CF composite was significantly (p < 0.05) associated with one or more oxidative stress and DNA repair gene polymorphisms evaluated either by SNP main effects and/or SNP-by-prescribed breast cancer treatment group interactions. Each computed GRS was found to be significantly (p < 0.001) related to its corresponding CF composite. All associations were positive suggesting that as overall genetic protection increases, CF composite score increases (indicating better performance).ConclusionsThese findings suggest that genetic variation in the oxidative stress and DNA repair pathways may play an important role in pre-adjuvant therapy CF in breast cancer survivors.
| S-EPMC4826652 | biostudies-literature
Project description:Primarily, the role of the aromatase inhibitors has been investigated in postmenopausal women with breast cancer, although it is also now being assessed in premenopausal patients following ovarian ablation/suppression. Aromatase inhibitors markedly suppress endogenous oestrogens without directly interacting with oestrogen receptors, and thus have a different mechanism of action to the antioestrogen, tamoxifen. The inhibitors may be divided into subgroups according to their structure (steroidal and nonsteroidal), and there appears to be a lack of cross-resistance between the classes of aromatase inhibitors enabling them to be used sequentially and potentially to prolong endocrine hormone therapy. In addition, with increased efficacy and favourable safety and tolerability profiles, the aromatase inhibitors are starting to challenge tamoxifen as first choice endocrine treatment in a number of settings. Potential differences in side-effect profiles may appear between the steroidal and nonsteroidal aromatase inhibitors when used in long-term settings. Thus, it has been suggested that the steroidal agents have favourable end organ effects; for example, the steroidal inhibitor, exemestane, has minimal negative effects on bone and lipid metabolism in animal and clinical studies. This paper provides an overview of the current and future roles of aromatase inhibitors for breast cancer treatment.
| S-EPMC2361691 | biostudies-other
Project description:BackgroundMusculoskeletal pain (MSKP) is the most reported symptom during treatment with aromatase inhibitors (AIs) for breast cancer. The mechanisms underlying MSKP are multidimensional and not well understood. The goals of this biological pathway analysis were to (1) gain an understanding of the genetic variation and biological mechanisms underlying MSKP with AI therapy and (2) identify plausible biological pathways and candidate genes for future investigation.MethodGenes associated with MSKP during AI therapy or genes involved in drug metabolism of and response to AIs were identified from the literature. Studies published through February 2019 were queried in PubMed®. The genes identified from the literature were entered into QIAGEN's Ingenuity® Pathway Analysis (IPA) software to generate canonical pathways, upstream regulators, and networks through a core analysis.ResultsThe 17 genes identified were ABCB1, ABCG1, CYP17A1, CYP19A1, CYP27B1, CYP2A6, CYP3A4, CYP3A5, ESR1, OATP1B1, OPG, RANKL, SLCO3A1, TCL1A, UGT2A1, UGT2B17, and VDR. These genes are involved in encoding bone-remodeling regulators, drug-metabolizing enzymes (cytochrome P450 family, UDP-glucuronosyltransferases family), or drug transporters (ATP-binding cassette transporters, organic anion transporters). Multiple plausible biological pathways (e.g., nicotine degradation, melatonin degradation) and candidate genes (e.g., NFKB, HSP90, AKT, ERK1/2, FOXA2) are proposed for future investigation based on the IPA results.ConclusionMultiple genes and molecular-level etiologies may contribute to MSKP with AI therapy in women with breast cancer. Our innovative combination of gene identification from the literature plus biological pathway analysis allowed for the emergence of novel candidate genes and biological pathways for future investigations.
| S-EPMC7273800 | biostudies-literature
Project description:Purposethis study was conducted to assess the impact of AIs on body mass index and high sensitivity as prognostic predictors to be incorporated into point of care technology (POCT) testing in postmenopausal breast cancer women after a 24 month follow up in Africa. An observational cohort study was conducted; including 126 female BC patients with stages ranging from 0-III initially subjected to AIs and subsequently followed up for 24 months. Multiple imputation model was conducted to predict missing data.ResultsRandom effects model was used to monitor the changes over the time. The study revealed stronger statistically association between BMI and homocysteine (p = 0.021, 95%CI: 0.0083 to 0.1029). Weight and total body fat were strongly associated after 24 months follow up. Hs-CRP was associated with BMI (p = 0.0001), and hs-CRP was associated with other biomedical markers such as calcium (p = 0.021, 95% CI: 0.01 to 0.10), phosphate (p = 0.039, 95%CI: 0.01 to 0.10), and ferritin (p = 0.002, 95%CI: 0.02 to 0.08) and calcium. The patients subjected to AIs are likely to develop cardiovascular adverse events. POCT of care strategy which include clinical, biomedical and genetic predictor's measurement is required to improve BC survivorship.
| S-EPMC10012500 | biostudies-literature