Variations in COMT and NTRK2 Influence Symptom Burden in Women Undergoing Breast Cancer Treatment.
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ABSTRACT:
SUBMITTER: Young EE
PROVIDER: S-EPMC5873314 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Breast cancer treatments can change women's hormonal milieu and alter their symptom experience. Little is known about associations between menopausal status and menopausal symptoms in women with breast cancer before surgery. OBJECTIVE:The purpose of this study was to evaluate for differences in occurrence, severity, and distress of symptoms between premenopausal and postmenopausal women before breast cancer surgery. METHODS:A total of 312 women with breast cancer completed the Menopausal Symptoms Scale, a self-report measure that evaluated the occurrence, severity, and distress of 46 common symptoms associated with menopause. Regression analyses were used to evaluate for between-group differences in these symptoms. RESULTS:Of the 312 patients enrolled, 37.4% (n = 116) were premenopausal, and 62.6% (n = 196) were postmenopausal. In the multivariate analysis that adjusted for 7 covariates, premenopausal patients reported higher occurrence rates for urinary frequency (P = .006) and reported lower occurrence rates for joint pain/stiffness (P = .011), difficulty falling asleep (P = .025), and vaginal dryness (P = .002). A significant interaction was found between age and menopausal status for hot flashes (P = .002), wake during the night (P = .025), and headache (P = .040). CONCLUSION:Regardless of menopausal status, women reported high occurrence rates for several menopausal symptoms. Associations between some symptom occurrence rates and menopausal status depended on the patients' age. IMPLICATIONS FOR PRACTICE:As part of a preoperative symptom assessment, clinicians need to consider a woman's menopausal status and salient demographic and clinical characteristics. The identification of women with a higher symptom burden will assist with more effective management.
| S-EPMC5866155 | biostudies-literature
Project description:Introduction Lifestyle-associated factors like physical activity (PA) play an important role in cancer prevention and oncology treatment outcomes. The aim of the study is to investigate the level of kinesiophobia (fear of movement) in breast cancer (BC) patients undergoing surgical treatment depending on socio-demographic variables, lifestyle before cancer diagnosis, stage and type of BC and comorbidities. Methods We interviewed 285 women (132 patients from Greater Poland Cancer Center – age: 55.7 ± 12.4; BMI: 26.7 ± 4.7 and 153 healthy women from control group – age: 49.0 ± 15.7; BMI: 25.7 ± 4.0) using Polish adaptation of the Tampa Scale of Kinesiophobia (TSK). Results Research results show that women with BC suffer from kinesiophobia (>37 points) signi!cantly. Approximately 3/4 of the surveyed women with BC did not know the World Health Organization (WHO) recommendations regarding the weekly dose of PA for healthy people and for people with cancer. Before cancer diagnosis more than a half of women (60%) performed PA in accordance with WHO recommendations. 7% less women performed PA during oncology treatment. Almost a half of patients are not physically active during cancer treatment and 1/5 of the respondents declared that they do not know yet if they will be physically active after oncology treatment. The level of kinesiophobia in BC women with comorbidities was the same as in the group of BC women without comorbidities. However, the highest levels of fear of movement have been observed among women with BC suffering also from osteoporosis, obesity and diabetes. In general, higher levels of kinesiophobia were reported among women in less advanced stages of the disease. There were no differences in the level of kinesiophobia depending on the type of BC (hormonally dependent luminal cancers vs. other types). The level of kinesiophobia did not differ between women who were physically active before BC diagnosis and women who were not. In terms of socio- demographic variables, we found one direct association between the level of kinesiophobia (pain) with age – the greater age, the higher level of pain kinesiophobia. Discussion Research on fear of movement in female oncology requires further research (including also chemotherapy, radiotherapy, immunotherapy and hormonal therapy) and in order to effectively eliminate hypokinetic attitudes at every stage of cancer treatment.
| S-EPMC9932589 | biostudies-literature
Project description:Catechol-O-methyltransferase (COMT) metabolizes catecholamines in different tissues. Polymorphisms in COMT gene can attenuate COMT activity and increase sensitivity to pain. Human studies exploring the effect of COMT polymorphisms on pain sensitivity have mostly included small, heterogeneous samples and have ignored several important single nucleotide polymorphisms (SNPs). This study examines the effect of COMT polymorphisms on experimental and postoperative pain phenotypes in a large ethnically homogeneous female patient cohort.Intensity of cold (+2-4°C) and heat (+48°C) pain and tolerance to cold pain were assessed in 1,000 patients scheduled for breast cancer surgery. Acute postoperative pain and oxycodone requirements were recorded. Twenty-two COMT SNPs were genotyped and their association with six pain phenotypes analyzed with linear regression.There was no association between any of the tested pain phenotypes and SNP rs4680. The strongest association signals were seen between rs165774 and heat pain intensity as well as rs887200 and cold pain intensity. In both cases, minor allele carriers reported less pain. Neither of these results remained significant after strict multiple testing corrections. When analyzed further, the effect of rs887200 was, however, shown to be significant and consistent throughout the cold pressure test. No evidence of association between the SNPs and postoperative oxycodone consumption was found.SNPs rs887200 and rs165774 located in the untranslated regions of the gene had the strongest effects on pain sensitivity. Their effect on pain is described here for the first time. These results should be confirmed in further studies and the potential functional mechanisms of the variants studied.
| S-EPMC4869072 | biostudies-literature
Project description:OBJECTIVES:To examine the association between phthalate exposure and two measures of uterine fibroid burden: diameter of largest fibroid and uterine volume. DESIGN:Pilot, cross-sectional study. SETTING:Academic medical center. PATIENT(S):Fifty-seven premenopausal women undergoing either hysterectomy or myomectomy for fibroids. INTERVENTION(S):None. MAIN OUTCOME MEASURE(S):The diameter of the largest fibroid and uterine dimensions were abstracted from medical records. Spot urine samples were analyzed for 14 phthalate biomarkers using mass spectrometry. We estimated associations between fibroid outcomes and individual phthalate metabolites, sum of di(2-ethylhexyl) phthalate metabolites (?DEHP), and a weighted sum of anti-androgenic phthalate metabolites (?AA Phthalates) using linear regression, adjusting for age, race/ethnicity, and body mass index. Fibroid outcomes were also examined dichotomously (divided at the median) using logistic regression. RESULTS:Most women were of black ethnicity, overweight or obese, and college educated. In multivariable models, higher levels of mono-hydroxyisobutyl phthalate, monocarboxyoctyl phthalate, monocarboxynonyl phthalate, mono(2-ethylhexyl) phthalate, mono(2-ethyl-5-hydroxyhexyl phthalate) (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), ?DEHP, and ?AA Phthalates were positively associated with uterine volume. Associations were most pronounced for individual DEHP metabolites (MEHHP, MEOHP, MECPP), ?DEHP, and ?AA Phthalates. For example, a doubling in ?DEHP and ?AA Phthalates was associated with 33.2% (95% confidence interval 6.6-66.5) and 26.8% (95% confidence interval 2.2-57.4) increase in uterine volume, respectively. There were few associations between phthalate biomarkers and fibroid size. CONCLUSIONS:Exposure to some phthalate biomarkers was positively associated with uterine volume, which further supports the hypothesis that phthalate exposures may be associated with fibroid outcomes. Additional studies are needed to confirm these relationships.
| S-EPMC6321778 | biostudies-literature
Project description:Catechol-O-methyl transferase (COMT) is an important estrogen-metabolizing enzyme, and common genetic variants in this gene could affect breast cancer risk. We conducted a large population-based case control study in Massachusetts, New Hampshire, and Wisconsin to examine six strategically selected COMT haplotype-tagging (ht) single nucleotide polymorphism (SNPs), including the val158met polymorphism (rs4680), in relation to breast cancer risk. Analyses were based on 1,655 Caucasian women with invasive breast cancer and 1,470 Caucasian controls. None of the six individual SNPs were associated with breast cancer risk. The global test for haplotype associations was nonsignificant (p-value=0.097), although two uncommon haplotypes present in 6% of the study population showed statistically significant inverse associations with risk. These results suggest that genetic variation in COMT has no significant association with breast cancer risk among Caucasian women.
| S-EPMC3086748 | biostudies-literature
Project description:BackgroundThe diagnosis of breast cancer and its subsequent treatment has significant impact on the woman's physical functioning, mental health and her well-being, and thereby causes substantial disruption to quality of life (QOL). Factors like patient education, spousal support and employment status, financial stability etc., have been found to influence QOL in the breast cancer patient. The present study attempts to identify the determinants of QOL in a cohort of Indian breast cancer patients.Patients and methodsFunctional Assessment of Cancer Therapy-Breast (FACT-B) Version 4 Malayalam was used to assess quality of life in 502 breast cancer patients undergoing treatment with curative intent. The data on social, demographic, disease, treatment, and follow-up were collected from case records. Data was analysed using Analysis of Variance (ANOVA) and multinomial logistic regression.ResultsThe mean age of the patients was 47.7 years with 44.6% of the women being pre-menopausal. The FACT-B mean score was 90.6 (Standard Deviation [SD] = 18.4). The mean scores of the subscales were - Physical well-being 19.6 (SD = 4.7), Social well-being 19.9 (SD = 5.3), Emotional well-being 14 (SD = 4.9), Functional well-being 13.0 (SD = 5.7), and the Breast subscale 23.8 (SD = 4.4). Younger women (< 45 years), women having unmarried children, nodal and/or metastatic disease, and those currently undergoing active treatment showed significantly poorer QOL scores in the univariate analysis. However multivariate analysis indicated that the religion, stage, pain, spouse education, nodal status, and distance travelled to reach the treatment centre as indicative of patient QOL.ConclusionQOL derangements are common in breast cancer patients necessitating the provisions for patient access to psychosocial services. However, because of the huge patient load, a screening process to identify those meriting intervention over the general population would be a viable solution.
| S-EPMC1261539 | biostudies-literature
Project description:RationaleIn symptomatic patients with COPD, the decision whether to initiate maintenance treatment with a single agent or a combination of long-acting bronchodilators remains unclear.ObjectiveTo investigate whether baseline symptomatic status influences response to tiotropium/olodaterol treatment.Materials and methodsPost hoc analysis of the randomized OTEMTO® studies (NCT01964352; NCT02006732), in which patients with moderate-to-severe COPD received placebo, tiotropium 5 µg, tiotropium/olodaterol 2.5/5 µg, or tiotropium/olodaterol 5/5 µg once daily for 12 weeks via the Respimat® inhaler (Boehringer Ingelheim, Ingelheim am Rhein, Germany). Impact of baseline symptomatic status (modified Medical Research Council [mMRC] score) on response to treatment with tiotropium/olodaterol 5/5 µg, tiotropium 5 µg, or placebo at Week 12 was assessed by St George's Respiratory Questionnaire (SGRQ) total score and response rate, transition dyspnea index (TDI) focal score and response rate, and trough forced expiratory volume in 1 second response.ResultsTiotropium/olodaterol improved SGRQ total scores and response rates compared with placebo and tiotropium for patients with baseline mMRC scores 0-1 and ≥2. For tiotropium/olodaterol vs tiotropium, greater improvements were observed for patients with mMRC ≥2 (SGRQ score adjusted mean treatment difference -3.44 [95% CI: -5.43, -1.46]; P=0.0007; SGRQ response rate ORs 2.09 [95% CI: 1.41, 3.10]; P=0.0002). Dyspnea, measured by TDI score, was consistently improved with tiotropium/olodaterol vs placebo for patients with mMRC scores 0-1 and ≥2 (adjusted mean treatment difference 1.63 [95% CI: 1.06, 2.20]; P<0.0001 and 1.60 [95% CI: 1.09, 2.10]; P<0.0001, respectively). In patients with mMRC scores 0-1 and ≥2, tiotropium/olodaterol consistently improved TDI response rate and lung function vs placebo and tiotropium.ConclusionsPatients with COPD with more severe baseline dyspnea appear to derive greater health status benefit with tiotropium/olodaterol compared with tiotropium alone.
| S-EPMC6324615 | biostudies-literature
Project description:PurposeHarms of prostate cancer treatment on urinary health related quality of life have been thoroughly studied. In this study we evaluated not only the harms but also the potential benefits of prostate cancer treatment in relieving the pretreatment urinary symptom burden.Materials and methodsIn American (1,021) and Spanish (539) multicenter prospective cohorts of men with localized prostate cancer we evaluated the effects of radical prostatectomy, external radiotherapy or brachytherapy in relieving pretreatment urinary symptoms and in inducing urinary symptoms de novo, measured by changes in urinary medication use and patient reported urinary bother.ResultsUrinary symptom burden improved in 23% and worsened in 28% of subjects after prostate cancer treatment in the American cohort. Urinary medication use rates before treatment and 2 years after treatment were 15% and 6% with radical prostatectomy, 22% and 26% with external radiotherapy, and 19% and 46% with brachytherapy, respectively. Pretreatment urinary medication use (OR 1.4, 95% CI 1.0-2.0, p = 0.04) and pretreatment moderate lower urinary tract symptoms (OR 2.8, 95% CI 2.2-3.6) predicted prostate cancer treatment associated relief of baseline urinary symptom burden. Subjects with pretreatment lower urinary tract symptoms who underwent radical prostatectomy experienced the greatest relief of pretreatment symptoms (OR 4.3, 95% CI 3.0-6.1), despite the development of deleterious de novo urinary incontinence in some men. The magnitude of pretreatment urinary symptom burden and beneficial effect of cancer treatment on those symptoms were verified in the Spanish cohort.ConclusionsMen with pretreatment lower urinary tract symptoms may experience benefit rather than harm in overall urinary outcome from primary prostate cancer treatment. Practitioners should consider the full spectrum of urinary symptom burden evident before prostate cancer treatment in treatment decisions.
| S-EPMC5501938 | biostudies-literature
Project description:Understanding the symptom burden trajectory for metastatic breast cancer patients can enable the provision of appropriate supportive care for symptom management. The aim of this study was to describe the longitudinal trajectories of symptom burden for metastatic breast cancer patients at the population-level. A cohort of 995 metastatic breast cancer patients with 16,146 Edmonton Symptom Assessment System (ESAS) assessments was constructed using linked population-level health administrative databases. The patient-reported ESAS total symptom distress score (TSDS) was studied over time using group-based trajectory modeling, and covariate influences on trajectory patterns were examined. Cohort patients experienced symptom burden that could be divided into six distinct trajectories. Patients experiencing a higher baseline TSDS were likely to be classified into trajectory groups with high, uncontrolled TSDS within the study follow-up period (χ2 (1, N = 995) = 136.25, p < 0.001). Compared to patients classified in the group trajectory with the highest relative TSDS (Group 6), patients classified in the lowest relative TSDS trajectory group (Group 1) were more likely to not have comorbidities (97.34% (for Groups 1-3) vs. 91.82% (for Group 6); p < 0.05), more likely to receive chemotherapy (86.52% vs. 80.50%; p < 0.05), and less likely to receive palliative care (52.81% vs. 79.25%; p < 0.0001). Receiving radiotherapy was a significant predictor of how symptom burden was experienced in all identified groups. Overall, metastatic breast cancer patients follow heterogeneous symptom burden trajectories over time, with some experiencing a higher, uncontrolled symptom burden. Understanding trajectories can assist in establishing risk-stratified care pathways for patients.
| S-EPMC7985757 | biostudies-literature
Project description:Depression and inflammation may independently promote breast cancer (BCa) disease progression and poorer clinical outcomes. Depression has been associated with increased levels of inflammatory markers in medically healthy individuals and patients with cancer. However, inconsistencies in study time frames complicate interpretation of results within specific cancer types. This study examined relationships between depressive symptoms and inflammation in women with early-stage BCa before beginning adjuvant treatment.Women with Stage 0-III BCa were recruited approximately 4 to 8 weeks after surgery. Depressive symptoms were assessed using the Hamilton Rating Scale for Depression, and blood samples were collected to quantify circulating levels of interleukin (IL)-1?, IL-6, and tumor necrosis factor ? (TNF-?) by enzyme-linked immunosorbent assay. Analyses of covariance were used to test for group differences (elevated versus low depressive symptoms) in levels of cytokines. Multiple regression analyses were used to examine relationships between continuous severity of depressive symptoms and levels of cytokines adjusting for relevant biobehavioral covariates.Thirty-six (40%) of 89 patients showed elevated levels of depressive symptoms and, in adjusted models, had marginally higher levels of IL-1? (mean [M] = 14.49 [95% confidence interval {CI} = 6.11-32.65] versus M = 4.68 [95% CI = 1.96-9.86] and IL-6 [M = 88.74 {95% CI = 33.28-233.96} versus M = 61.52 {95% CI = 27.44-136.40}]) significantly higher levels of TNF-? (M = 17.07 [95% CI = 8.27-34.32] versus M = 6.94 [95% CI = 3.58-12.80]) than did women with low depressive symptoms. Across the spectrum of depressive symptoms, greater magnitude of depressive symptoms was related to greater levels of IL-1? (? = 0.06, p = .006, R = 0.25) and TNF-? (? = 0.06, p = .003, R = 0.27).Postsurgery and preadjuvant treatment for early-stage BCa, depressive symptoms covary with elevated levels of multiple proinflammatory cytokines. Findings have implications for psychosocial and biological interventions concurrently focusing on depression and inflammation.NCT01422551.
| S-EPMC4696897 | biostudies-literature