Acute and late onset cognitive dysfunction associated with chemotherapy in women with breast cancer.
BACKGROUND
Growing evidence supports cognitive dysfunction associated with standard dose chemotherapy in breast cancer survivors. We determined the incidence, nature, and chronicity of cognitive dysfunction in a prospective longitudinal randomized phase 3 treatment trial for patients with T1-3, N0-1, M0 breast cancer receiving 5-fluorouracil, doxorubicin, and cyclophosphamide with or without paclitaxel.


METHODS
Forty-two patients underwent a neuropsychological evaluation including measures of cognition, mood, and quality of life. Patients were scheduled to be assessed before chemotherapy, during and shortly after chemotherapy, and 1 year after completion of chemotherapy.


RESULTS
Before chemotherapy, 21% (9 of 42) evidenced cognitive dysfunction. In the acute interval, 65% (24 of 37) demonstrated cognitive decline. At the long-term evaluation, 61% (17 of 28) evidenced cognitive decline after cessation of treatment. Within this group of patients, 71% (12 of 17) evidenced continuous decline from the acute interval, and, notably, 29% (5 of 17) evidenced new delayed cognitive decline. Cognitive decline was most common in the domains of learning and memory, executive function, and processing speed. Cognitive decline was not associated with mood or other measured clinical or demographic characteristics, but late decline may be associated with baseline level of performance.


CONCLUSIONS
Standard dose systemic chemotherapy is associated with decline in cognitive function during and shortly after completion of chemotherapy. In addition, delayed cognitive dysfunction occurred in a large proportion of patients. These findings are consistent with a developing body of translational animal research demonstrating both acute and delayed structural brain changes as well as functional changes associated with common chemotherapeutic agents such as 5-fluorouracil.
Wefel
Jeffrey S
JS
The University of Texas M. D. Anderson Cancer Center, Section of Neuropsychology, Department of Neuro-Oncology, Houston, Texas 77230-1402, USA. jwefel@mdanderson.org
Saleeba
Angele K
AK
Buzdar
Aman U
AU
Meyers
Christina A
CA
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000523:psychology; D003072:Cognition Disorders / Q000139:chemically induced*; D005260:Female; D006801:Humans; D008568:Memory; D008875:Middle Aged; D009483:Neuropsychological Tests; D011788:Quality of Life; D013997:Time Factors