Individual Differences in Well-Being in Older Breast Cancer Survivors

Older women who survive breast cancer may differ significantly in their long-term well-being. Using a risk and protective factors model, we studied predictors of well-being in 127 women age 70 and above with a history of at least one year\u27s survival of breast cancer. Mean post-cancer survivorship was 5.1 years. Using life satisfaction, depression and general health perceptions as outcome variables, we assessed whether demographic variables, cancer-related variables, health status and psychosocial resources predicted variability in well-being using correlational and hierarchical regression analyses. Higher age predicted increased depression but was not associated with life satisfaction or general health perceptions. Cancer-related variables, including duration of survival, and type of cancer treatment, were not significantly associated with survivors\u27 well-being. Poorer health status was associated with poorer well-being in all three dependent variables. After controlling for demographics, cancer-related variables, and health status, higher levels of psychosocial resources including optimism, mastery, spirituality and social support predicted better outcome in all three dependent variables. While many older women survive breast cancer without severe sequelae, there is considerable variability in their well-being after survivorship. Successful intervention with older breast cancer survivors might include greater attention not only to cancer-specific concerns, but also attention to geriatric syndromes and functional impairment, and enhancement of protective psychosocial resources

Trajectories of Quality of Life after Hematopoietic Cell Transplantation: Secondary Analysis of BMT CTN 0902 Data

Quality of life is increasingly recognized as an important secondary endpoint of hematopoietic cell transplantation (HCT). The current study examined the extent to which attrition results in biased estimates of patient quality of life. The study also examined whether patients differ in terms of trajectories of quality of life in the first six months post-transplant. A secondary data analysis was conducted of 701 participants who enrolled in the Blood and Marrow Transplantation Clinical Trials Network (BMT CTN) 0902 trial. Participants completed the SF-36, a measure of quality of life, prior to transplant and 100 and 180 days post-transplant. Results indicated that attrition resulted in slightly biased overestimates of quality of life but the amount of overestimation remained stable over time. Patients could be grouped into three distinct classes based on physical quality of life: 1) low and stable; 2) average and declining, then stable; and 3) average and stable. Four classes of patients emerged for mental quality of life: 1) low and stable; 2) average, improving, then stable; 3) higher than average (by almost 1 SD) and stable; and 4) average and stable. Taken together, these data provide a more comprehensive understanding of quality of life that can be used to educate HCT recipients and their caregivers

Genetic interactions affecting human gene expression identified by variance association mapping

Non-additive interaction between genetic variants, or epistasis, is a possible explanation for the gap between heritability of complex traits and the variation explained by identified genetic loci. Interactions give rise to genotype dependent variance, and therefore the identification of variance quantitative trait loci can be an intermediate step to discover both epistasis and gene by environment effects (GxE). Using RNA-sequence data from lymphoblastoid cell lines (LCLs) from the TwinsUK cohort, we identify a candidate set of 508 variance associated SNPs. Exploiting the twin design we show that GxE plays a role in ∼70% of these associations. Further investigation of these loci reveals 57 epistatic interactions that replicated in a smaller dataset, explaining on average 4.3% of phenotypic variance. In 24 cases, more variance is explained by the interaction than their additive contributions. Using molecular phenotypes in this way may provide a route to uncovering genetic interactions underlying more complex traits.DOI: http://dx.doi.org/10.7554/eLife.01381.001

CFH and ARMS2 genetic risk determines progression to neovascular age-related macular degeneration after antioxidant and zinc supplementation

We evaluated the influence of an antioxidant and zinc nutritional supplement [the Age-Related Eye Disease Study (AREDS) formulation] on delaying or preventing progression to neovascular AMD (NV) in persons with age-related macular degeneration (AMD). AREDS subjects (n = 802) with category 3 or 4 AMD at baseline who had been treated with placebo or the AREDS formulation were evaluated for differences in the risk of progression to NV as a function of complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) genotype groups. We used published genetic grouping: a two-SNP haplotype risk-calling algorithm to assess CFH, and either the single SNP rs10490924 or 372_815del443ins54 to mark ARMS2 risk. Progression risk was determined using the Cox proportional hazard model. Genetics–treatment interaction on NV risk was assessed using a multiiterative bootstrap validation analysis. We identified strong interaction of genetics with AREDS formulation treatment on the development of NV. Individuals with high CFH and no ARMS2 risk alleles and taking the AREDS formulation had increased progression to NV compared with placebo. Those with low CFH risk and high ARMS2 risk had decreased progression risk. Analysis of CFH and ARMS2 genotype groups from a validation dataset reinforces this conclusion. Bootstrapping analysis confirms the presence of a genetics–treatment interaction and suggests that individual treatment response to the AREDS formulation is largely determined by genetics. The AREDS formulation modifies the risk of progression to NV based on individual genetics. Its use should be based on patient-specific genotype

Cognitive function prior to systemic therapy and subsequent well‐being in older breast cancer survivors: Longitudinal findings from the Thinking and Living with Cancer Study

ObjectiveTo investigate the relationships between self‐reported and objectively measured cognitive function prior to systemic therapy and subsequent well‐being outcomes over 24 months in older breast cancer survivors.MethodsData were from 397 women aged 60 to 98 diagnosed with non‐metastatic breast cancer in the Thinking and Living with Cancer Study recruited from 2010‐2016. Cognitive function was measured at baseline (following surgery, prior to systemic therapy) using neuropsychological assessments of attention, processing speed, and executive function (APE), learning and memory (LM), and the self‐reported FACT‐Cog scale. Well‐being was measured using the FACT‐G functional, physical, social, and emotional well‐being domain scales at baseline and 12 and 24 months later, scaled from 0 (low) to 100 (high). Linear mixed‐effects models assessed the relationships between each of baseline APE, LM, and FACT‐Cog quartiles with well‐being scores over 24 months, adjusted for confounding variables.ResultsAt baseline, older survivors in the lowest APE, LM, and FACT‐Cog score quartiles experienced poorer global well‐being than those in the highest quartiles. At 24 months, older survivors tended to improve in well‐being, and there were no differences according to baseline APE or LM scores. At 24 months, mean global well‐being was 80.3 (95% CI: 76.2‐84.3) among those in the lowest vs 86.6 (95% CI: 83.1‐90.1) in the highest FACT‐cog quartile, a clinically meaningful difference of 6.3 points (95% CI: 1.5‐11.1).ConclusionsAmong older breast cancer survivors, self‐reported, but not objective cognitive impairments, were associated with lower global well‐being over the first 2 years of survivorship.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155908/1/pon5376.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155908/2/pon5376_am.pd

Autonomous Detection of Particles and Tracks in Optical Images

During its initial orbital phase in early 2019, the Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx) asteroid sample return mission detected small particles apparently emanating from the surface of the near-Earth asteroid (101955) Bennu in optical navigation images. Identification and characterization of the physical and dynamical properties of these objects became a mission priority in terms of both spacecraft safety and scientific investigation. Traditional techniques for particle identification and tracking typically rely on manual inspection and are often time-consuming. The large number of particles associated with the Bennu events and the mission criticality rendered manual inspection techniques infeasible for long-term operational support. In this work, we present techniques for autonomously detecting potential particles in monocular images and providing initial correspondences between observations in sequential images, as implemented for the OSIRIS-REx mission.Comment: 23 pages, 10 figure

Prediction of cognitive decline in older breast cancer survivors: the Thinking and Living with Cancer study

PURPOSE: Cancer survivors commonly report cognitive declines after cancer therapy. Due to the complex etiology of cancer-related cognitive decline (CRCD), predicting who will be at risk of CRCD remains a clinical challenge. We developed a model to predict breast cancer survivors who would experience CRCD after systematic treatment. METHODS: We used the Thinking and Living with Cancer study, a large ongoing multisite prospective study of older breast cancer survivors with complete assessments pre-systemic therapy, 12 months and 24 months after initiation of systemic therapy. Cognition was measured using neuropsychological testing of attention, processing speed, and executive function (APE). CRCD was defined as a 0.25 SD (of observed changes from baseline to 12 months in matched controls) decline or greater in APE score from baseline to 12 months (transient) or persistent as a decline 0.25 SD or greater sustained to 24 months. We used machine learning approaches to predict CRCD using baseline demographics, tumor characteristics and treatment, genotypes, comorbidity, and self-reported physical, psychosocial, and cognitive function. RESULTS: Thirty-two percent of survivors had transient cognitive decline, and 41% of these women experienced persistent decline. Prediction of CRCD was good: yielding an area under the curve of 0.75 and 0.79 for transient and persistent decline, respectively. Variables most informative in predicting CRCD included apolipoprotein E4 positivity, tumor HER2 positivity, obesity, cardiovascular comorbidities, more prescription medications, and higher baseline APE score. CONCLUSIONS: Our proof-of-concept tool demonstrates our prediction models are potentially useful to predict risk of CRCD. Future research is needed to validate this approach for predicting CRCD in routine practice settings

Symptom burden among older breast cancer survivors: The Thinking and Living With Cancer (TLC) study

Background: Little is known about longitudinal symptom burden and its consequences for well-being, and if lifestyle moderates burden in older survivors. Methods: We report on 36-month data from survivors 60+ with newly diagnosed non-metastatic breast cancer and non-cancer controls recruited August 2010-June 2016. Symptom burden was a sum of self-reported symptoms/diseases: pain (yes/no), fatigue (FACT-fatigue), cognitive (FACT-cog), sleep problems (yes/no), depression (CES-D), anxiety (STAI), and cardiac problems and neuropathy (yes/no). Well-being was measured using the FACT-G, scaled from 0–100. Lifestyle included smoking, alcohol use, BMI, physical activity, and leisure activities. Mixed models assessed relationships between treatment group (chemotherapy +/− hormonal, hormonal only, control) and symptom burden, lifestyle, and covariates. Separate models tested the effects of fluctuations in symptom burden and lifestyle on function. Results: All groups reported high baseline symptoms, and levels remained high over time; survivor-control differences were most notable for cognitive and sleep problems, anxiety, and neuropathy. The adjusted burden score was highest among chemotherapy-exposed survivors, followed by hormonal therapy vs. controls (p<.001). Burden score was related to physical, emotional, and functional well-being (e.g., survivors with lower vs. higher burden scores had 12.4-point higher physical well-being score). The composite lifestyle score was not related to symptom burden or well-being, but physical activity was significantly associated with each outcome (<.005). Conclusions: Cancer and its treatments are associated with a higher level of actionable symptoms and greater loss of well-being over time in older breast cancer survivors than comparable non-cancer populations, suggesting the need for surveillance and opportunities for intervention

Pre-treatment psychoneurological symptoms and their association with longitudinal cognitive function and quality of life in older breast cancer survivors

Context Symptoms affect quality of life (QOL), functional status, and cognitive function in cancer survivors, but older survivors are understudied. Objectives To identify prototypical pre-systemic therapy psychoneurological symptom clusters among older breast cancer survivors, and determine whether these symptom clusters predicted cognition and QOL over time. Methods Women with newly diagnosed non-metastatic breast cancer (n=319) and matched non-cancer controls (n=347) aged 60+ completed questionnaires and neuropsychological tests before systemic therapy and 12- and 24-months later. Latent class analysis identified clusters of survivors based upon their pre-therapy depression, anxiety, fatigue, sleep disturbance, and pain. Linear mixed-effects models examined changes in objective cognition, perceived cognition, and functional status (instrumental activities of daily living (IADL) disability, functional well-being, and breast cancer-specific QOL) by group, controlling for covariates. Results Nearly one-fifth of older survivors were classified as having a high pre-therapy symptoms (n=51; 16%); the remainder had a low symptoms (n=268; 84%); both groups improved over time on all outcomes. However, compared to the low symptom group and controls, survivors with high symptoms had lower baseline objective cognition and lower perceived cognition at baseline and 24-months, lower functional well-being at baseline and 12-months, greater IADL disability at baseline, and lower breast cancer-specific QOL at all time points (all p<0.05). Conclusion Nearly one-fifth of older breast cancer survivors had high psychoneurological symptoms at diagnosis, which, predict clinically meaningful decrements in perceived cognition and function in the first 24 months post-diagnosis. Pre-treatment psychoneurological symptom clusters could identify survivors for monitoring or intervention

Cancer-Related Cognitive Outcomes Among Older Breast Cancer Survivors in the Thinking and Living With Cancer Study

Purpose To determine treatment and aging-related effects on longitudinal cognitive function in older breast cancer survivors. Methods Newly diagnosed nonmetastatic breast cancer survivors (n = 344) and matched controls without cancer (n = 347) 60 years of age and older without dementia or neurologic disease were recruited between August 2010 and December 2015. Data collection occurred during presystemic treatment/control enrollment and at 12 and 24 months through biospecimens; surveys; self-reported Functional Assessment of Cancer Therapy-Cognitive Function; and neuropsychological tests that measured attention, processing speed, and executive function (APE) and learning and memory (LM). Linear mixed-effects models tested two-way interactions of treatment group (control, chemotherapy with or without hormonal therapy, and hormonal therapy) and time and explored three-way interactions of ApoE (ε4+ v not) by group by time; covariates included baseline age, frailty, race, and cognitive reserve. Results Survivors and controls were 60 to 98 years of age, were well educated, and had similar baseline cognitive scores. Treatment was related to longitudinal cognition scores, with survivors who received chemotherapy having increasingly worse APE scores (P = .05) and those initiating hormonal therapy having lower LM scores at 12 months (P = .03) than other groups. These group-by-time differences varied by ApoE genotype, where only ε4+ survivors receiving hormone therapy had short-term decreases in adjusted LM scores (three-way interaction P = .03). For APE, the three-way interaction was not significant (P = .14), but scores were significantly lower for ε4+ survivors exposed to chemotherapy (−0.40; 95% CI, −0.79 to −0.01) at 24 months than ε4+ controls (0.01; 95% CI, 0.16 to 0.18; P < .05). Increasing age was associated with lower baseline scores on all cognitive measures (P < .001); frailty was associated with baseline APE and self-reported decline (P < .001). Conclusion Breast cancer systemic treatment and aging-related phenotypes and genotypes are associated with longitudinal decreases in cognitive function scores in older survivors. These data could inform treatment decision making and survivorship care planning