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Browsing by Author "Cohen, Harvey J."
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Item Applying a Life Course Biological Age Framework to Improving the Care of Individuals with Adult Cancers: Review and Research Recommendations(American Medical Association, 2021) Mandelblatt, Jeanne S.; Ahles, Tim A.; Lippman, Marc E.; Isaacs, Claudine; Adams-Campbell, Lucile; Saykin, Andrew J.; Cohen, Harvey J.; Carroll, Judith; Radiology and Imaging Sciences, School of MedicineImportance: The practice of oncology will increasingly involve the care of a growing population of individuals with midlife and late-life cancers. Managing cancer in these individuals is complex, based on differences in biological age at diagnosis. Biological age is a measure of accumulated life course damage to biological systems, loss of reserve, and vulnerability to functional deterioration and death. Biological age is important because it affects the ability to manage the rigors of cancer therapy, survivors' function, and cancer progression. However, biological age is not always clinically apparent. This review presents a conceptual framework of life course biological aging, summarizes candidate measures, and describes a research agenda to facilitate clinical translation to oncology practice. Observations: Midlife and late-life cancers are chronic diseases that may arise from cumulative patterns of biological aging occurring over the life course. Before diagnosis, each new patient was on a distinct course of biological aging related to past exposures, life experiences, genetics, and noncancer chronic disease. Cancer and its treatments may also be associated with biological aging. Several measures of biological age, including p16INK4a, epigenetic age, telomere length, and inflammatory and body composition markers, have been used in oncology research. One or more of these measures may be useful in cancer care, either alone or in combination with clinical history and geriatric assessments. However, further research will be needed before biological age assessment can be recommended in routine practice, including determination of situations in which knowledge about biological age would change treatment, ascertaining whether treatment effects on biological aging are short-lived or persistent, and testing interventions to modify biological age, decrease treatment toxic effects, and maintain functional abilities. Conclusions and relevance: Understanding differences in biological aging could ultimately allow clinicians to better personalize treatment and supportive care, develop tailored survivorship care plans, and prescribe preventive or ameliorative therapies and behaviors informed by aging mechanisms.Item Associations between lifestyle factors and quality of life among older long-term breast, prostate, and colorectal cancer survivors(Wiley, 2009) Mosher, Catherine E.; Sloane, Richard; Morey, Miriam C.; Snyder, Denise Clutter; Cohen, Harvey J.; Miller, Paige E.; Demark-Wahnefried, WendyBACKGROUND: Older cancer survivors are at increased risk for secondary cancers, cardiovascular disease, obesity, and functional decline and, thus, may benefit from health-related interventions. However, to the authors' knowledge, little is known regarding the health behaviors of older cancer survivors and the associations of those behaviors with quality-of-life outcomes, especially during the long-term post-treatment period. METHODS: In total, 753 older (aged ≥65 years) long-term survivors (≥5 years postdiagnosis) of breast, prostate, and colorectal cancer completed 2 baseline telephone interviews to assess their eligibility for a diet and exercise intervention trial. The interviews assessed exercise, diet, weight status, and quality of life. RESULTS: Older cancer survivors reported a median of 10 minutes of moderate-to-vigorous exercise per week, and only 7% had Healthy Eating Index scores >80 (indicative of healthful eating habits relative to national guidelines). Despite their suboptimal health behaviors, survivors reported mental and physical quality of life that exceeded age-related norms. Greater exercise and better diet quality were associated with better physical quality-of-life outcomes (eg, better vitality and physical functioning; P < .05), whereas greater body mass index was associated with reduced physical quality of life (P < .001). CONCLUSIONS: The current results indicated a high prevalence of suboptimal health behaviors among older, long-term survivors of breast, prostate, and colorectal cancer who were interested in lifestyle modification. In addition, the findings pointed to the potential negative impact of obesity and the positive impact of physical activity and a healthy diet on physical quality of life in this population. Cancer 2009.Item Associations between longitudinal changes in sleep disturbance and depressive and anxiety symptoms during the COVID-19 virus pandemic among older women with and without breast cancer in the thinking and living with breast cancer study(Wiley, 2022) Bethea, Traci N.; Zhai, Wanting; Zhou, Xingtao; Ahles, Tim A.; Ahn, Jaeil; Cohen, Harvey J.; Dilawari, Asma A.; Graham, Deena M.A.; Jim, Heather S.L.; McDonald, Brenna C.; Nakamura, Zev M.; Patel, Sunita K.; Rentscher, Kelly E.; Root, James; Saykin, Andrew J.; Small, Brent J.; Van Dyk, Kathleen M.; Mandelblatt, Jeanne S.; Carroll, Judith E.; Radiology and Imaging Sciences, School of MedicinePurpose: Several studies have reported sleep disturbances during the COVID-19 virus pandemic. Little data exist about the impact of the pandemic on sleep and mental health among older women with breast cancer. We sought to examine whether women with and without breast cancer who experienced new sleep problems during the pandemic had worsening depression and anxiety. Methods: Breast cancer survivors aged ≥60 years with a history of nonmetastatic breast cancer (n = 242) and frequency-matched noncancer controls (n = 158) active in a longitudinal cohort study completed a COVID-19 virus pandemic survey from May to September 2020 (response rate 83%). Incident sleep disturbance was measured using the restless sleep item from the Center for Epidemiological Studies-Depression Scale (CES-D). CES-D score (minus the sleep item) captured depressive symptoms; the State-Anxiety subscale of the State Trait Anxiety Inventory measured anxiety symptoms. Multivariable linear regression models examined how the development of sleep disturbance affected changes in depressive or anxiety symptoms from the most recent prepandemic survey to the pandemic survey, controlling for covariates. Results: The prevalence of sleep disturbance during the pandemic was 22.3%, with incident sleep disturbance in 10% and 13.5% of survivors and controls, respectively. Depressive and anxiety symptoms significantly increased during the pandemic among women with incident sleep disturbance (vs. no disturbance) (β = 8.16, p < 0.01 and β = 6.14, p < 0.01, respectively), but there were no survivor-control differences in the effect. Conclusion: Development of sleep disturbances during the COVID-19 virus pandemic may negatively affect older women's mental health, but breast cancer survivors diagnosed with the nonmetastatic disease had similar experiences as women without cancer.Item Elevated C-Reactive Protein and Subsequent Patient-Reported Cognitive Problems in Older Breast Cancer Survivors: The Thinking and Living With Cancer Study(American Society of Clinical Oncology, 2023) Carroll, Judith E.; Nakamura, Zev M.; Small, Brent J.; Zhou, Xingtao; Cohen, Harvey J.; Ahles, Tim A.; Ahn, Jaeil; Bethea, Traci N.; Extermann, Martine; Graham, Deena; Isaacs, Claudine; Jim, Heather S. L.; Jacobsen, Paul B.; McDonald, Brenna C.; Patel, Sunita K.; Rentscher, Kelly; Root, James; Saykin, Andrew J.; Tometich, Danielle B.; Van Dyk, Kathleen; Zhai, Wanting; Breen, Elizabeth C.; Mandelblatt, Jeanne S.; Radiology and Imaging Sciences, School of MedicinePurpose: To examine longitudinal relationships between levels of C-reactive protein (CRP) and cognition in older breast cancer survivors and noncancer controls. Methods: English-speaking women age ≥ 60 years, newly diagnosed with primary breast cancer (stage 0-III), and frequency-matched controls were enrolled from September 2010 to March 2020; women with dementia, neurologic disorders, and other cancers were excluded. Assessments occurred presystemic therapy/enrollment and at annual visits up to 60 months. Cognition was measured using the Functional Assessment of Cancer Therapy-Cognitive Function and neuropsychological testing. Mixed linear effect models tested for survivor-control differences in natural log (ln)-transformed CRP at each visit. Random effect-lagged fluctuation models tested directional effects of ln-CRP on subsequent cognition. All models controlled for age, race, study site, cognitive reserve, obesity, and comorbidities; secondary analyses evaluated if depression or anxiety affected results. Results: There were 400 survivors and 329 controls with CRP specimens and follow-up data (average age of 67.7 years; range, 60-90 years). The majority of survivors had stage I (60.9%), estrogen receptor-positive (87.6%) tumors. Survivors had significantly higher adjusted mean ln-CRP than controls at baseline and 12-, 24-, and 60-month visits (all P < .05). Higher adjusted ln-CRP predicted lower participant-reported cognition on subsequent visits among survivors, but not controls (P interaction = .008); effects were unchanged by depression or anxiety. Overall, survivors had adjusted Functional Assessment of Cancer Therapy-Cognitive Function scores that were 9.5 and 14.2 points lower than controls at CRP levels of 3.0 and 10.0 mg/L. Survivors had poorer neuropsychological test performance (v controls), with significant interactions with CRP only for the Trails B test. Conclusion: Longitudinal relationships between CRP and cognition in older breast cancer survivors suggest that chronic inflammation may play a role in development of cognitive problems. CRP testing could be clinically useful in survivorship care.Item Impact of taxane-based chemotherapy among older women with breast cancer on cognition and quality of life: a longitudinal pooled analysis(Springer, 2022) Small, Brent J.; Lange, Marie; Zhai, Wanting; Ahn, Jaeil; Ahles, Tim A.; Carroll, Judith E.; Cohen, Harvey J.; Graham, Deena; Extermann, Martine; Heutte, Natacha; Jim, Heather S. L.; McDonald, Brenna C.; Patel, Sunita K.; Root, James C.; Saykin, Andrew J.; Van Dyk, Kathleen; Zhou, Xingtao; Mandelblatt, Jeanne; Joly, Florence; Thinking Living with Cancer C. O. G.-Age Studies; Radiology and Imaging Sciences, School of MedicinePurpose: Older cancer patients are susceptible to long-term effects of chemotherapy, including cancer-related cognitive decline and impairments to quality of life. Taxane-based chemotherapies are associated with physical declines among older women and may negatively impact cognitive performance. We sought to examine whether changes in objective and subjective measures of cognitive performance and well-being differ among older breast cancer survivors as a function of taxane-based chemotherapy treatment regimens. Methods: Individual-level data were pooled and harmonized from two large prospective studies of older (greater than 60 years) breast cancer survivors. Assessments were conducted prior to systemic therapy and up to 36 months after. Cognitive performance was assessed with objective (working memory, processing speed, and executive functions) and subjective tests and physical, emotional, and functional well-being were also assessed. Results: One hundred and sixty-seven (M age = 67.3 years) women with 116 receiving chemotherapy with taxanes and 51 without taxanes contributed data. Declines in subjective cognition for both groups were significant between pre-treatment and 12-month follow-up. Significant improvements were seen on a measure of objective cognition (working memory) from 12 to 36 months. Measures of well-being improved from prior to systemic therapy to 12 months. Longitudinal changes across all measures did not vary as a function of receipt of taxane-based treatment. Conclusion: Older women who received treatment with taxanes did not have greater declines in cognitive performance or well-being than women receiving other chemotherapy regimens. Despite older cancer survivors being at greater risk for negative outcomes, treatment with taxane-based chemotherapies does not appear to exacerbate these health consequences.Item Loneliness and mental health during the COVID‐19 pandemic in older breast cancer survivors and noncancer controls(Wiley, 2021-10-01) Rentscher, Kelly E.; Zhou, Xingtao; Small, Brent J.; Cohen, Harvey J.; Dilawari, Asma A.; Patel, Sunita K.; Bethea, Traci N.; Van Dyk, Kathleen M.; Nakamura, Zev M.; Ahn, Jaeil; Zhai, Wanting; Ahles, Tim A.; Jim, Heather S.L.; McDonald, Brenna C.; Saykin, Andrew J.; Root, James C.; Graham, Deena M.A.; Carroll, Judith E.; Mandelblatt, Jeanne S.; Radiology and Imaging Sciences, School of MedicineBackground: The coronavirus disease 2019 (COVID-19) pandemic has had wide-ranging health effects and increased isolation. Older with cancer patients might be especially vulnerable to loneliness and poor mental health during the pandemic. Methods: The authors included active participants enrolled in the longitudinal Thinking and Living With Cancer study of nonmetastatic breast cancer survivors aged 60 to 89 years (n = 262) and matched controls (n = 165) from 5 US regions. Participants completed questionnaires at parent study enrollment and then annually, including a web-based or telephone COVID-19 survey, between May 27 and September 11, 2020. Mixed-effects models were used to examine changes in loneliness (a single item on the Center for Epidemiologic Studies-Depression [CES-D] scale) from before to during the pandemic in survivors versus controls and to test survivor-control differences in the associations between changes in loneliness and changes in mental health, including depression (CES-D, excluding the loneliness item), anxiety (the State-Trait Anxiety Inventory), and perceived stress (the Perceived Stress Scale). Models were adjusted for age, race, county COVID-19 death rates, and time between assessments. Results: Loneliness increased from before to during the pandemic (0.211; P = .001), with no survivor-control differences. Increased loneliness was associated with worsening depression (3.958; P < .001) and anxiety (3.242; P < .001) symptoms and higher stress (1.172; P < .001) during the pandemic, also with no survivor-control differences. Conclusions: Cancer survivors reported changes in loneliness and mental health similar to those reported by women without cancer. However, both groups reported increased loneliness from before to during the pandemic that was related to worsening mental health, suggesting that screening for loneliness during medical care interactions will be important for identifying all older women at risk for adverse mental health effects of the pandemic.Item Plasma levels of interleukin-6 mediate neurocognitive performance in older breast cancer survivors: The Thinking and Living With Cancer study(Wiley, 2023) Mandelblatt, Jeanne S.; Small, Brent J.; Zhou, Xingtao; Nakamura, Zev M.; Cohen, Harvey J.; Ahles, Tim A.; Ahn, Jaeil; Bethea, Traci N.; Extermann, Martine; Graham, Deena; Isaacs, Claudine; Jim, Heather S. L.; Jacobsen, Paul B.; McDonald, Brenna C.; Patel, Sunita K.; Rentscher, Kelly E.; Root, James C.; Saykin, Andrew J.; Tometich, Danielle B.; Van Dyk, Kathleen; Zhai, Wanting; Breen, Elizabeth C.; Carroll, Judith E.; Radiology and Imaging Sciences, School of MedicineBackground: Immune activation/inflammation markers (immune markers) were tested to explain differences in neurocognition among older breast cancer survivors versus noncancer controls. Methods: Women >60 years old with primary breast cancer (stages 0-III) (n = 400) were assessed before systemic therapy with frequency-matched controls (n = 329) and followed annually to 60 months; blood was collected during annual assessments from 2016 to 2020. Neurocognition was measured by tests of attention, processing speed, and executive function (APE). Plasma levels of interleukin-6 (IL-6), IL-8, IL-10, tumor necrosis factor α (TNF-α), and interferon γ were determined using multiplex testing. Mixed linear models were used to compare results of immune marker levels by survivor/control group by time and by controlling for age, racial/ethnic group, cognitive reserve, and study site. Covariate-adjusted multilevel mediation analyses tested whether survivor/control group effects on cognition were explained by immune markers; secondary analyses examined the impact of additional covariates (e.g., comorbidity and obesity) on mediation effects. Results: Participants were aged 60-90 years (mean, 67.7 years). Most survivors had stage I (60.9%) estrogen receptor-positive tumors (87.6%). Survivors had significantly higher IL-6 levels than controls before systemic therapy and at 12, 24, and 60 months (p ≤ .001-.014) but there were no differences for other markers. Survivors had lower adjusted APE scores than controls (p < .05). Levels of IL-6, IL-10, and TNF-α were related to APE, with IL-6 explaining part of the relationship between survivor/control group and APE (p = .01). The magnitude of this mediation effect decreased but remained significant (p = .047) after the consideration of additional covariates. Conclusions: Older breast cancer survivors had worse long-term neurocognitive performance than controls, and this relationship was explained in part by elevated IL-6.Item Symptom burden among older breast cancer survivors: The Thinking and Living With Cancer (TLC) study(Wiley, 2020-03-15) Mandelblatt, Jeanne S.; Zhai, Wanting; Ahn, Jaeil; Small, Brent J.; Ahles, Tim A.; Carroll, Judith E.; Denduluri, Neelima; Dilawari, Asma; Extermann, Martine; Graham, Deena; Hurria, Arti; Isaacs, Claudine; Jacobsen, Paul B.; Jim, Heather S. L.; Luta, George; McDonald, Brenna C.; Patel, Sunita K.; Root, James C.; Saykin, Andrew J.; Tometich, Danielle B.; Zhou, Xingtao; Cohen, Harvey J.; Radiology and Imaging Sciences, School of MedicineBackground: 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.