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

Abstract

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.

Sleep disturbance and neurocognitive outcomes in older patients with breast cancer: Interaction with genotype

“…This prior research points to a 2‐hit effect of an APOE ε4 carrier status and sleep disruption on neurofibrillary tangles and the incidence of AD in noncancer populations . APOE ε4 has also been reported in association with cognitive declines in cancer patient populations . Our findings support a sleep– APOE ε4 carrier status interaction effect on learning and memory in older breast cancer survivors and suggests potential parallels between cancer‐related cognitive decline and AD.…”

“…We included 345 women recruited between August 1, 2010, and December 31, 2015. The study is ongoing and has been described elsewhere . Briefly, women with a history of stroke, head injury, a major axis I psychiatric disorder, or a neurodegenerative disorder were ineligible.…”

“…APOE genotypes (rs429358 determining whether the subject was an ε4 carrier) were also obtained from DNA for all samples via independent single‐nucleotide polymorphism testing. Further details on the assays have been described previously …”

“…The study is ongoing and has been described elsewhere. 23 Briefly, women with a history of stroke, head injury, a major axis I psychiatric disorder, or a neurodegenerative disorder were ineligible. Those with a history of other cancers were excluded if they had received active treatment less than 5 years before enrollment or ever had chemotherapy or hormonal therapy.…”

Longitudinal Relationship Between Frailty and Cognition in Patients 50 Years and Older with Breast Cancer

“…In the second study, also by Mandelblatt and colleagues, breast cancer patients aged 60 and older were compared with matched controls without cancer, and assessment included perceived and objective cognitive measures at baseline and 12 and 24 months. Frailty was also assessed in this study at baseline using an adapted Searle's deficits accumulation index.…”