A B S T R A C T PurposeTo determine if older patients with breast cancer have cognitive impairment before systemic therapy. Patients and MethodsParticipants were patients with newly diagnosed nonmetastatic breast cancer and matched friend or community controls age Ͼ 60 years without prior systemic treatment, dementia, or neurologic disease. Participants completed surveys and a 55-minute battery of 17 neuropsychological tests. Biospecimens were obtained for APOE genotyping, and clinical data were abstracted. Neuropsychological test scores were standardized using control means and standard deviations (SDs) and grouped into five domain z scores. Cognitive impairment was defined as any domain z score two SDs below or Ն two z scores 1.5 SDs below the control mean. Multivariable analyses evaluated pretreatment differences considering age, race, education, and site; comparisons between patient cases also controlled for surgery. ResultsThe 164 patient cases and 182 controls had similar neuropsychological domain scores. However, among patient cases, those with stage II to III cancers had lower executive function compared with those with stage 0 to I disease, after adjustment (P ϭ .05). The odds of impairment were significantly higher among older, nonwhite, less educated women and those with greater comorbidity, after adjustment. Patient case or control status, anxiety, depression, fatigue, and surgery were not associated with impairment. However, there was an interaction between comorbidity and patient case or control status; comorbidity was strongly associated with impairment among patient cases (adjusted odds ratio, 8.77; 95% CI, 2.06 to 37.4; P ϭ .003) but not among controls (P ϭ .97). Only diabetes and cardiovascular disease were associated with impairment among patient cases. ConclusionThere 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.