Cognitive deficits after postoperative adjuvant chemotherapy for breast carcinoma

Cancer. 1999 Feb 1;85(3):640-50. doi: 10.1002/(sici)1097-0142(19990201)85:3<640::aid-cncr14>;2-g.


Background: A number of patients who have undergone adjuvant (CMF) chemotherapy for operative primary breast carcinoma have reported impaired cognitive function, sometimes even years after completion of therapy. The possible role of cytostatic treatment as a causative factor has scarcely been investigated. The objective of the current study was to examine the late effects on neuropsychologic functioning of CMF adjuvant chemotherapy given to patients with breast carcinoma.

Methods: Thirty-nine breast carcinoma patients who had been treated with adjuvant CMF (6 courses) followed (n = 20) by 3 years of tamoxifen 20 mg daily or not (n = 19) were examined with neuropsychologic tests and interviews. The control group consisted of 34 age-matched axillary lymph node negative breast carcinoma patients who received the same surgical and radiation therapy but no systemic adjuvant treatment. The CMF patients were examined a median of 1.9 years after the sixth CMF course, and the controls a median of 2.4 years after surgery of the primary tumor.

Results: Patients treated with CMF reported significantly more problems with concentration (31% vs. 6%, P = 0.007) and with memory (21% vs. 3%, P = 0.022) than the control patients. No relation was found between reported complaints and results on the neuropsychologic tests. Impairment in cognitive function was found in 28% of the patients treated with chemotherapy compared with 12% of the patients in the control group (odds ratio 6.4 [95% confidence interval 1.5-27.6] P = 0.013). Hormonal therapy had no influence on patients' self-reports of symptoms or cognitive function. Cognitive impairment following chemotherapy was noticed in a broad domain of functioning, including attention, mental flexibility, speed of information processing, visual memory, and motor function.

Conclusions: Breast carcinoma patients treated with adjuvant CMF chemotherapy have a significantly higher risk of late cognitive impairment than breast carcinoma patients not treated with chemotherapy (OR 6.4). This cognitive impairment is unaffected by anxiety, depression, fatigue, and time since treatment, and not related to the self-reported complaints of cognitive dysfunction.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Attention / drug effects
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / surgery
  • Chemotherapy, Adjuvant / adverse effects
  • Cognition Disorders / chemically induced*
  • Cognition Disorders / diagnosis
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Depression / chemically induced
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Humans
  • Methotrexate / administration & dosage
  • Methotrexate / adverse effects
  • Middle Aged
  • Neuropsychological Tests
  • Quality of Life
  • Socioeconomic Factors


  • Cyclophosphamide
  • Fluorouracil
  • Methotrexate

Supplementary concepts

  • CMF regimen