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. 2018 Oct 3;36(32):JCO1800140.
doi: 10.1200/JCO.18.00140. Online ahead of print.

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

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Free PMC article

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

Jeanne S Mandelblatt et al. J Clin Oncol. .
Free PMC article

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.

Figures

Fig 1.
Fig 1.
(A) Sample for evaluation of cognition in older breast cancer survivors and (B) matched controls without cancer. Participants were excluded if they failed the cognitive screen (at baseline). The percentage who consented and refused was calculated among those alive and eligible to continue the study at each time point. Eligibility for continuing in the study was the same as enrollment eligibility and included development of a neurologic disease (eg, stroke, Parkinson’s disease) and a diagnosis of cancer. Survivors who were diagnosed with breast cancer recurrence were excluded from assessment for the 6 months before diagnosis of recurrence. Participants may have refused an interview at one time point but then completed later interviews. Most participants completed two or three assessments (64% completed three, 21% completed two, and 15% completed baseline only). No significant differences existed in age, frailty, apolipoprotein E ε4 status, or self-reported cognition by number of completed assessments. Those completing baseline only tended to have slightly lower baseline attention, processing speed, and executive function and learning and memory scores than those completing two or more assessments and to be a survivor versus a control, which potentially underestimated declines in mean post-treatment 12- and 24-month scores. SD, standard deviation.
Fig 2.
Fig 2.
Adjusted mean cognitive scores over time for older breast cancer survivors and controls without cancer. Adjusted mean cognitive domain scores on the basis of least squares means from linear mixed-effects models show scores at baseline, 12 months, and 24 months for three treatment groups, including survivors who received chemotherapy with or without hormonal therapy, survivors who received only hormonal therapy, and controls. The models included as fixed effects time; group; apolipoprotein E genotype; all two- and three-way interactions for group, apolipoprotein E, and time; baseline age; frailty; standardized Wide Range Achievement Test 4 score; race; and recruitment site. Adjusted mean scores are shown by treatment group and time for the (A) attention, processing speed, and executive function (APE) domain (P = .05 for group-by-time interaction) and (B) learning and memory (LM) domain (P = .03 for group-by-time interaction) for the genotypes combined. (C) Self-reported cognition scores on the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog), with higher scores indicating better cognitive function. Declines of 5% to 7%, or 7 to 10 points, on this 148-point scale are considered clinically meaningful. Tables 2 and 3 include the 95% CIs for each mean score at each time point and for each outcome.
Fig 3.
Fig 3.
Adjusted mean cognitive scores over time for older breast cancer survivors and controls without cancer by apolipoprotein E (ApoE) status. Adjusted mean cognitive domain scores on the basis of least squares means from linear mixed-effects models show scores at baseline, 12 months, and 24 months for three treatment groups, including survivors who received chemotherapy with or without hormonal therapy, survivors who received only hormonal therapy, and controls. The models included as fixed effects time; group; ApoE genotype; all two- and three-way interactions for group, ApoE, and time; baseline age; frailty; standardized Wide Range Achievement Test 4 score; race; and recruitment site. (A) Results for the attention, processing speed, and executive function (APE) domain for group-by-time-by-ApoE ε4 positivity, where adjusted means are plotted for participants who are ApoE ε4+ and ApoE ε4− (P = .14 for three-way interaction). (B) Results for the learning and memory (LM) domain for group-by-time-by-ApoE ε4 positivity, where adjusted means are plotted for participants who are ApoE ε4+ and ApoE ε4− (P = .03 for three-way interaction). (C) Results for self-reported cognition on the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) scale for group-by-time-by-ApoE ε4 positivity, where adjusted means are plotted for participants who are ApoE ε4+ and ApoE ε4− (P not significant for three-way interaction). Declines of 5% to 7%, or 7 to 10 points, on this 148-point scale are considered clinically meaningful. Tables 2 and 3 include the 95% CIs for each mean score at each time point for each outcome.

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