Cognitive Outcomes Among Older Survivors of Breast Cancer

Key Points

  • Chemotherapy and hormonal therapy were associated with lower cognitive function scores at 12 months among survivors.
  • APE scores at 24 months were lower among ApoE ε4+ survivors who had received chemotherapy vs ε4+ controls.

In a study (Thinking and Living with Cancer) reported in the Journal of Clinical Oncology, Mandelblatt et al found that poorer cognitive function in older survivors of breast cancer was associated with chemotherapy, hormone therapy, and ApoE genotype. The ApoE ε4 allele has been associated with inflammation and increased risk of Alzheimer disease.

Study Details

The study included 347 newly diagnosed nonmetastatic breast cancer survivors (n = 344) and matched controls (n = 347) aged ≥ 60 years without dementia or neurologic disease recruited from several U.S. centers between August 2010 and December 2015. Participants were assessed with neuropsychological tests measuring attention, processing speed, and executive function (APE) and learning and memory (LM) at baseline and at 12 and 24 months after treatment. Linear mixed-effects models were used to analyze two-way interactions of treatment group (control, chemotherapy with or without hormonal therapy, and hormonal therapy) and time and three-way interactions of ApoE (ε4+ vs not) by group by time; covariates included baseline age, frailty, race, and cognitive reserve. Mean age was 68 years in both groups. The ε4 genotype was present in 20% of patients and 25% of controls.

Cognitive Function Outcomes

Treatment was associated with longitudinal differences in cognitive function among survivors, with those receiving chemotherapy having with lower APE scores (P = .05) and those receiving hormonal therapy having lower LM scores at 12 months (P = .03) compared with other groups. In analysis of 3-way interaction, these group-by-time differences varied according to ApoE genotype, with ε4+ survivors receiving hormone therapy having short-term decreases in adjusted LM scores (three-way interaction P = .03). The three-way interaction was not significant for APE scores (P = .14). However, ε4+ survivors who had received chemotherapy had lower APE scores at 24 months vs ε4+ controls (P < .05).

Increasing age was associated with lower baseline scores on all cognitive measures (P < .001). Baseline frailty was associated with lower baseline APE scores and self-reported decline in cognitive function on the Functional Assessment of Cancer Therapy-Cognitive Function (P < .001).

The investigators concluded, “Breast cancer systemic treatment and aging-related phenotypes [eg, frailty] 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.”  

The study was supported by National Cancer Institute grants and a grant from National Institute on Aging.

Jeanne S. Mandelblatt, MD, MPH, of Georgetown Lombardi Comprehensive Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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