Cognitive deficits following breast cancer diagnosis and subsequent chemotherapy with cyclophosphamide, methotrexate, and fluorouracil (CMF) can be long-lasting, suggest the findings of a study in which women who underwent this regimen more than 20 years earlier performed, on average, worse than random population controls on neuropsychological tests. 

Adjuvant chemotherapy for breast cancer can have adverse effects on cognition shortly after administration, but the long-term effects are largely unknown. With the widespread use of chemotherapy for early-stage breast cancer and improved survival for these patients, the question of whether treatment affects cognition is increasingly relevant, pointed out study investigators Sanne B. Schagen, PhD, of the Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital in Amsterdam, the Netherlands, and fellow investigators in their report for Journal of Clinical Oncology (

Schagen and colleagues evaluated the cognitive performance of 196 women, aged 50 to 80 years, who had undergone six cycles of adjuvant CMF chemotherapy an average of 21 years earlier. (CMF, no longer the standard of care for breast cancer, was commonly used between 1976 and 1995.) Compared with 1,509 women who had never had cancer, the former chemotherapy patients performed significantly worse on cognitive tests of immediate and delayed verbal memory (the ability to recall words), processing speed, executive functioning, and psychomotor speed (coordination of thinking and hand movement, such as putting pegs in a board). These women also had significantly more memory complaints on two of three measures that could not be explained by cognitive test performance, but were weakly correlated with mood. Although the cancer survivors experienced fewer symptoms of depression than did the controls, both groups had scores indicative of clinical depression.

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“The pattern of cognitive problems is largely similar to that observed in patients shortly after cessation of chemotherapy,” noted the researchers.

Although Schagen and associates say their findings do not suggest that breast cancer survivors who underwent CMF chemotherapy need to be monitored more closely for cognitive difficulties, information about the possible long-term effects of their treatment might help guide referral to appropriate support services if these women do experience cognitive problems.