Dataset Information

Apolipoprotein E genotype and cognitive function in postmenopausal women with early-stage breast cancer.

ABSTRACT: To examine the role of apolipoprotein E (APOE) genotype in the cognitive function of postmenopausal women with early-stage breast cancer prior to initiation of adjuvant therapy and over time with treatment.Longitudinal, genetic association study.Urban university cancer center.Three cohorts of postmenopausal women: 37 women with breast cancer receiving chemotherapy and anastrozole, 41 women with breast cancer receiving anastrozole alone, and 50 healthy women.Cognitive function was evaluated three times during a 12-month period using a comprehensive neuropsychological test battery. Participants were genotyped and classified based on the presence or absence of at least one APOE e4 allele. Multiple linear regression was used to determine if APOE genotype accounted for observed variability in cognitive function data.APOE genotype, breast cancer treatment, and cognitive function.Performance or changes in performance on tasks of executive function, attention, verbal learning and memory, and visual learning and memory were found to be influenced by APOE genotype and/or interactions between APOE genotype and study cohort.The results indicate that cognitive function in postmenopausal women with breast cancer is modified by APOE genotype and the combination of APOE genotype and treatment.APOE genotype, along with other biomarkers, may be used in the future to assist nurses in identifying women with breast cancer most at risk for cognitive decline.

SUBMITTER: Koleck TA

PROVIDER: S-EPMC4406250 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Apolipoprotein E genotype and cognitive function in postmenopausal women with early-stage breast cancer.

Koleck Theresa A TA Bender Catherine M CM Sereika Susan M SM Ahrendt Gretchen G Jankowitz Rachel C RC McGuire Kandace P KP Ryan Christopher M CM Conley Yvette P YP

Oncology nursing forum 20141101 6

<h4>Purpose/objectives</h4>To examine the role of apolipoprotein E (APOE) genotype in the cognitive function of postmenopausal women with early-stage breast cancer prior to initiation of adjuvant therapy and over time with treatment.<h4>Design</h4>Longitudinal, genetic association study.<h4>Setting</h4>Urban university cancer center.<h4>Sample</h4>Three cohorts of postmenopausal women: 37 women with breast cancer receiving chemotherapy and anastrozole, 41 women with breast cancer receiving anast ...[more]

PMID: 25355028

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Project description:BackgroundEarly discontinuation of aromatase inhibitors (AIs) is common and leads to poor outcomes but is challenging to predict. In the Exemestane and Letrozole Pharmacogenetics trial, a high rate of early discontinuation due to intolerance was observed. We hypothesized that early changes in patient-reported outcomes (PROs) predict AI discontinuation and that biochemical factors are associated with changes in PROs.Patients and methodsPostmenopausal women with early-stage breast cancer enrolled in a prospective randomized trial of exemestane versus letrozole completed questionnaires at baseline and serially over 24 months to assess overall quality of life (EuroQOL Visual Analog Scale [VAS]); mood; and multiple symptoms, including a musculoskeletal symptom cluster. A joint mixed-effects/survival model was used to estimate the effect of the change in PROs on AI discontinuation. Associations between biochemical factors and change in PROs were examined.ResultsA total of 490 patients were analyzed. Worsening of EuroQOL VAS and the musculoskeletal cluster were associated with the highest risk for early discontinuation (hazard ratio [HR], 2.77 [95% confidence interval (CI), 2.72-2.81; p = .015]; HR, 4.39 [95% CI, 2.40-8.02; p < .0001], respectively). Pharmacokinetics and estrogen metabolism were not consistently associated with change in PRO measures. No clinically significant differences in any PRO between AIs were observed.ConclusionChanges in PROs early during AI therapy were associated with treatment discontinuation. Identification of these changes could be used to target interventions in patients at high risk for early discontinuation.Implications for practiceEarly changes in patient-reported outcomes (PROs) can predict nonpersistence to aromatase inhibitor therapy. If used in clinical practice, PROs might identify women at highest risk for early discontinuation and allow for interventions to improve tolerance before significant toxicities develop. Further research is needed to improve capturing PROs in routine clinical practice.

Project description:PurposeAromatase inhibitors (AIs) prolong survival for postmenopausal women with hormone receptor-positive breast cancer (HR + BC) but also burden patients with symptoms, a major reason for suboptimal AI adherence. This study characterizes inter-relationships among symptom measures; describes neuropsychological symptom burden trajectories; and identifies trajectory group membership predictors for postmenopausal women prescribed anastrozole for HR + BC.MethodsThis study utilized prospectively collected data from a cohort study. Relationships among various self-reported symptom measures were examined followed by a factor analysis to reduce data redundancy before trajectory analysis. Four neuropsychological scales/subscales were rescaled (range 0-100) and averaged into a neuropsychological symptom burden (NSB) score, where higher scores indicated greater symptom burden. Group-based trajectory modeling characterized NSB trajectories. Trajectory group membership predictors were identified using multinomial logistic regression.ResultsWomen (N = 360) averaged 61 years old, were mostly White, and diagnosed with stage I HR + BC. Several measures were correlated temporally but four neuropsychological measures had strong correlations and dimensional loadings. These four measures, combined for the composite NSB, averaged (mean ± standard deviation) 17.4 ± 12.9, 18.0 ± 12.7, 19.5 ± 12.8, and 19.8 ± 13.0 at pre-anastrozole, 6, 12, and 18 months post-initiation, respectively. However, the analysis revealed five NSB trajectories-low-stable, low-increasing, moderate-stable, high-stable, and high-increasing. Younger age and baseline medication categories (pre-anastrozole), including anti-depressants, analgesics, anti-anxiety, and no calcium/vitamin D, predicted the higher NSB trajectories.ConclusionThis study found relationships among neuropsychological symptom measures and distinct trajectories of self-reported NSB with pre-anastrozole predictors. Identifying symptom trajectories and their predictors at pre-anastrozole may inform supportive care strategies via symptom management interventions to optimize adherence for women with HR + BC.

Project description:ObjectiveIn a sample of 368 postmenopausal women, we (1) determined within-cohort and between-cohort relationships between adjuvant systemic therapy for breast cancer and self-reported cognitive function during the first 18 months of therapy and (2) evaluated the influence of co-occurring symptoms, neuropsychological function, and other covariates on relationships.MethodsWe evaluated self-reported cognitive function, using the Patient Assessment of Own Functioning Inventory (PAOFI), and potential covariates (e.g., co-occurring symptom scores and neuropsychological function z-scores) in 158 women receiving aromatase inhibitor (AI) therapy alone, 104 women receiving chemotherapy followed by AI therapy, and 106 non-cancer controls. Patients were assessed before systemic therapy and then every 6 months, for a total of four assessments over 18 months. Controls were assessed at matched time points. Mixed-effects modeling was used to determine longitudinal relationships.ResultsControlling for covariates, patients enrolled before chemotherapy reported poorer global cognitive function (p < 0.001), memory (p < 0.001), language and communication (p < 0.001), and sensorimotor function (p = 0.002) after chemotherapy. These patients reported poorer higher-level cognitive and intellectual functions from before chemotherapy to 12 months after initiation of AI therapy (p < 0.001). Higher levels of depressive symptoms (p < 0.001), anxiety (p < 0.001), and fatigue (p = 0.040) at enrollment were predictors of poorer cognitive function over time. PAOFI total score was a predictor of executive function (p = 0.048) and visual working memory (p = 0.005) z-scores, controlling for covariates.ConclusionsFindings provide further evidence of poorer self-reported cognitive function after chemotherapy and of relationships between co-occurring symptoms and cognitive changes. AI therapy alone does not have an impact on self-reported cognitive function. Copyright © 2015 John Wiley & Sons, Ltd.

Project description:The impact of chemotherapy on cognition among elderly patients has received little attention, although such patients are more prone to presenting with age-related cognitive deficits and/or cognitive decline during chemotherapy. The present study assessed the cognitive function in older adults treated for early-stage breast cancer (EBC).The participants were newly diagnosed EBC patients aged ?65 years without previous systemic treatment or neurological or psychiatric disease and matched healthy controls. They underwent two assessments: before starting adjuvant therapy and after the end of chemotherapy (including doxorubicin ± docetaxel [CT+ group], n = 58) or radiotherapy for patients who did not receive chemotherapy (CT- group, n = 61), and at the same interval for the healthy controls (n = 62). Neuropsychological and geriatric assessments were performed. Neuropsychological data were analyzed using the Reliable Change Index.Forty-nine percent of the patients (mean age, 70 ± 4 years) had objective cognitive decline after adjuvant treatment that mainly concerned working memory. Among these patients, 64% developed a cognitive impairment after adjuvant treatment. Comorbidity was not associated with cognitive decline. No significant difference in objective cognitive decline was found between the two groups of patients; however, the CT+ group had more subjective cognitive complaints after treatment (p = .008). The oldest patients (aged 70-81 years) tended to have more objective decline with docetaxel (p = .05).This is the largest published study assessing cognitive function in older adults with EBC that included a group of patients treated with modern chemotherapy regimens. Approximately half the patients had objective cognitive decline after adjuvant treatment. The oldest patients were more likely to have cognitive decline with chemotherapy, particularly with docetaxel.This is the largest published study assessing cognitive function in older adults with early-stage breast cancer that included a group of patients treated with modern chemotherapy regimens. Approximately half the patients had objective cognitive decline after adjuvant treatment. The oldest patients were more likely to have cognitive decline with chemotherapy, particularly with docetaxel. Cognitive deficits could affect patients' quality of life and their compliance to treatment. Assessing cognitive dysfunctions in the elderly cancer population is a challenge in clinical practice, but it could influence the choice of the most appropriate therapy, including the use of oral drugs.

Project description:IntroductionAdjuvant endocrine therapy induces bone loss and increases fracture risk in women with hormone-receptor positive, early-stage breast cancer (EBC). We aimed to update a previous position statement on the management of aromatase inhibitors (AIs) induced bone loss and now included premenopausal women.MethodsWe conducted a systematic literature search of the medical databases from January 2017 to May 2020 and assessed 144 new studies.ResultsExtended use of AIs beyond 5 years leads to persistent bone loss in breast cancer extended adjuvant trials and meta-analyses. In addition to bone mineral density (BMD), vertebral fracture assessment (VFA) and trabecular bone score (TBS) were shown to independently predict fracture risk in real life prospective studies. FRAX® tool does not seem to be reliable for assessing fracture risk in CTIBL. In premenopausal women, there is strong evidence that intravenous zoledronate prevents bone loss but weak conflicting evidence on reducing disease recurrence from independent randomised controlled trials (RCTs). In postmenopausal women, the strongest evidence for fracture prevention is for denosumab based on a well-powered RCT while there is strong evidence for bisphosphonates (BPs) to prevent and reduce CTIBL but no convincing data on fractures. Adjuvant denosumab has failed to show anticancer benefits in a large, well-designed RCT.Discussion and conclusionsExtended use of AIs and persistent bone loss from recent data reinforce the need to evaluate fracture risk in EBC women initiated on AIs. Fracture risk should be assessed with clinical risk factors and BMD along with VFA, but FRAX is not adapted to CTIBL. Anti-resorptive therapy should be considered in those with a BMD T-score < -2.0 SD or with ≥ 2 clinical risk factors including a BMD T-score < -1.0 SD. In premenopausal women, intravenous zoledronate is the only drug reported to prevent bone loss and may have additional anticancer benefits. In postmenopausal women, either denosumab or BPs can be prescribed for fracture prevention with pertinent attention to the rebound phenomenon after stopping denosumab. Adjuvant BPs, in contrast to denosumab, have shown high level evidence for reducing breast cancer recurrence in high-risk post-MP women which should be taken into account when choosing between these two.

Project description:ObjectiveTo examine the interaction between APOE genotypes and both treated and untreated hypertension on cognitive function in an updated analysis of Nurses' Health Study (NHS) data.DesignAt baseline (1995-2001) and 3 biennial follow-up assessments over ~6 years, cognitive function was assessed.Setting and participants8300 NHS participants aged 70+ years underwent a cognitive battery, which comprised 6 tests including the Telephone Interview for Cognitive Status (TICS) and tests of verbal memory, category fluency, and working memory.MeasuresWe estimated the mean differences in average cognitive scores across up to 4 assessments using multiple linear regression. We also tested for interaction between APOE e4 allele carrier status and hypertension overall, as well as for apparently untreated and treated hypertension.ResultsWe confirmed that, compared with those with APOE e3/3 genotype, APOE e4 allele carriers scored lower by 0.55 units on the average TICS score (95%CI:-0.67,-0.43). We also observed a significantly worse average TICS score among women with untreated hypertension compared with women without hypertension (difference = -0.23, 95%CI:-0.37,-0.09), while no significant difference was observed for women with treated hypertension. Significant interaction was detected between the APOE e4 allele and untreated hypertension (p-int = 0.02 for the TICS; p-int = 0.045 for global score), but not with treated hypertension. Specifically, compared with normotensive women with the APOE e3/3 genotype, APOE e4 allele carriers with treated hypertension scored lower by 0.50 units (95%CI:-0.69,-0.31); however, the APOE e4 allele carriers with untreated hypertension scored lower by 1.02 units on the TICS score (95%CI:-1.29, -0.76). This interaction of APOE e4 and untreated hypertension was also consistently observed for the global score.ConclusionsWomen with hypertension and at least one APOE e4 allele had worse average cognitive function compared with women without hypertension with the e3/3 genotype; this difference was amplified among APOE e4 allele carriers with untreated hypertension.

Dataset Information

Apolipoprotein E genotype and cognitive function in postmenopausal women with early-stage breast cancer.

Publications

Apolipoprotein E genotype and cognitive function in postmenopausal women with early-stage breast cancer.

Similar Datasets

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