Greater Risk of Pretreatment Cognitive Impairment in Older Breast Cancer Patients With More Advanced Disease and Greater Comorbidity


Key Points

  • There were no differences between cancer patients and controls in pretreatment neuropsychological function or cognitive impairment.
  • Among patients, greater impairment was observed among those with higher disease stage, greater comorbidity, and diabetes or cardiovascular disease.

In a study reported in the Journal of Clinical Oncology, Mandelblatt and colleagues attempted to determine whether cognitive impairment is present in older patients with breast cancer prior to systemic therapy. They found that although there were no global differences in cognitive function between patients and controls, subgroups of patients had impaired function in association with greater comorbidity and tumor burden.

Study Details

Participants were patients (n = 164) from four U.S. study sites with newly diagnosed nonmetastatic breast cancer and matched friend or community controls (n = 182) aged ≥ 60 years without prior systemic treatment, dementia, or neurologic disease. Participants completed a 55-minute battery of 17 neuropsychological tests with the domains of: attention, working memory, and processing speed; language; executive functioning; learning and memory; and visual-spatial functioning.

Test scores were standardized using control means and standard deviations and grouped into five domain z scores. Cognitive impairment was defined as any domain z score 2 standard deviations below or ≥ 2 z scores 1.5 standard deviations below the control mean. Multivariate analyses adjusted for age, race, education, and site, and comparisons between patients controlled for surgery.

Similar Neuropsychological Functioning

Patients had significantly higher levels of anxiety, depression, and fatigue and lower quality of life vs controls (all P < .005), but there were no differences in cognition between patients and controls. There were no differences between patients and controls in unadjusted or adjusted means of neuropsychological test domain scores. However, patients with stage II to III cancers had lower executive function compared with those with stage 0 to I disease after adjustment (P < .05).

Effect of Comorbidity

There were no differences in unadjusted rates of cognitive impairment between patients and controls (14% vs 15%, P = .81). However, patients with high comorbidity levels had a higher rate of impairment than patients with low comorbidity levels (25.7% vs4.4%), whereas controls had similar rates of impairment in high vs low comorbidity groups (17.5% vs 12.8%; P < .001 for overall comparison).

There was no association of surgery, anxiety, depression, fatigue, health habits and physical activity, or current physical or emotional function with impairment in either group. The adjusted odds of impairment were not related to patient or control status, but were significantly higher in patients who were older (adjusted odds ratio [OR] = 1.10 per 1 year increase), of nonwhite race (OR = 3.38), and with lower educational levels (OR = 0.81 per 1 year increase; all P < .001). There was an interaction between comorbidity and patient or control status, with ≥ 2 vs < 2 comorbidities being associated with a significantly higher risk of cognitive impairment among patients (adjusted OR = 8.77, P = .003) but not among controls (OR = 0.98, P = .97).

Exploratory analysis showed that there were no differences between patients and controls in proportion with diabetes (10.4% vs 7.7%; P = .39) or cardiovascular disease (52.4% vs 47.3%, P = .34). However, the cognitive impairment rate was significantly higher in patients with vs without diabetes (41% vs 11%, P = .003) and with vs without cardiovascular disease (22% vs 5%, P = .002), whereas there was no association between these conditions and impairment in controls.

The investigators concluded, “There were no overall differences between patients with breast cancer and controls before systemic treatment, but there may be pretreatment cognitive impairment within subgroups of patient cases with greater tumor or comorbidity burden.”

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

The study was supported by grants from the National Institutes of Health and National Cancer Institute. For full disclosures of the study authors, visit

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®.