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.

Background Little is known about longitudinal symptom burden, its consequences for well‐being, and whether lifestyle moderates the burden in older survivors. Methods The authors report on 36‐month data from survivors aged ≥60 years with newly diagnosed, nonmetastatic breast cancer and noncancer controls recruited from August 2010 through June 2016. Symptom burden was measured as the sum of self‐reported symptoms/diseases as follows: pain (yes or no), fatigue (on the Functional Assessment of Cancer Therapy [FACT]‐Fatigue scale), cognitive (on the FACT‐Cognitive scale), sleep problems (yes or no), depression (on the Center for Epidemiologic Studies Depression scale), anxiety (on the State‐Trait Anxiety Inventory), and cardiac problems and neuropathy (yes or no). Well‐being was measured using the FACT‐General scale, with scores from 0 to 100. Lifestyle included smoking, alcohol use, body mass index, physical activity, and leisure activities. Mixed models assessed relations between treatment group (chemotherapy with or without hormone therapy, hormone therapy only, and controls) 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; differences between survivors and controls were most notable for cognitive and sleep problems, anxiety, and neuropathy. The adjusted burden score was highest among chemotherapy‐exposed survivors, followed by hormone therapy‐exposed survivors versus controls (P < .001). The burden score was related to physical, emotional, and functional well‐being (eg, survivors with lower vs higher burden scores had 12.4‐point higher physical well‐being scores). The composite lifestyle score was not related to symptom burden or well‐being, but physical activity was significantly associated with each outcome (P < .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 in comparable noncancer populations, suggesting the need for surveillance and opportunities for intervention.

Context. Symptoms affect quality of life (QOL), functional status, and cognitive function in cancer survivors, but older survivors are understudied.Objectives. The objectives of this study were to identify prototypical presystemic 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 nonmetastatic breast cancer (n ¼ 319) and matched noncancer controls (n ¼ 347) aged 60þ years completed questionnaires and neuropsychological tests before systemic therapy and 12 and 24 months later. Latent class analysis identified clusters of survivors based on their pretherapy 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 disability, functional well-being, and breast cancerespecific QOL) by group, controlling for covariates.Results. Nearly one-fifth of older survivors were classified as having high pretherapy symptoms (n ¼ 51; 16%); the remainder had low symptoms (n ¼ 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 Instrumental Activities of Daily Living disability at baseline, and lower breast cancerespecific 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 predicted clinically meaningful decrements in perceived cognition and function in the first 24 months after diagnosis. Pretreatment psychoneurological symptom clusters could identify survivors for monitoring or intervention.

Background Sleep disturbance and genetic profile are risks for cognitive decline in noncancer populations, yet their role in cancer‐related cognitive problems remains understudied. This study examined whether sleep disturbance was associated with worse neurocognitive outcomes in breast cancer survivors and whether sleep effects on cognition varied by genotype. Methods Newly diagnosed female patients (n = 319) who were 60 years old or older and had stage 0 to III breast cancer were recruited from August 2010 to December 2015. Assessments were performed before systemic therapy and 12 and 24 months later. Neuropsychological testing measured attention, processing speed, executive function, learning, and memory; self‐perceived cognitive functioning was also assessed. Sleep disturbance was defined by self‐report of routine poor or restless sleep. Genotyping included APOE, BDNF, and COMT polymorphisms. Random effects fluctuation models tested associations of between‐person and within‐person differences in sleep, genotype, and sleep‐genotype interactions and cognition and controlled for age, reading level, race, site, and treatment. Results One‐third of the patients reported sleep disturbances at each time point. There was a sleep‐APOE ε4 interaction (P = .001) in which patients with the APOE ε4 allele and sleep disturbances had significantly lower learning and memory scores than those who were APOE ε4‐negative and without sleep disturbances. There was also a sleep disturbance–COMT genotype interaction (P = .02) in which COMT Val carriers with sleep disturbances had lower perceived cognition than noncarriers. Conclusions Sleep disturbance was common and was associated with worse cognitive performance in older breast cancer survivors, especially those with a genetic risk for cognitive decline. Survivorship care should include sleep assessments and interventions to address sleep problems.