Chemotherapy-related cognitive changes had significant associations with older age and lower baseline cognitive reserve, data from a case-control study of breast cancer patients showed.
Older patients with lower cognitive reserve who were treated with chemotherapy scored significantly lower on tests of processing speed than women treated only with tamoxifen (P=0.003) and a healthy control group (P<0.001), investigators reported in an article published online in the Journal of Clinical Oncology.
Chemotherapy also appeared to have a temporary adverse effect on verbal ability, which differed significantly from the tamoxifen-only and control groups at one month (P=0.01). Verbal ability improved, however, during two subsequent follow-up evaluations of patients who received chemotherapy.
The findings suggest that pretreatment factors, as well as various aspects of breast cancer and its therapy, have an impact on cognitive functioning, the researchers wrote.
"This study helps clarify two issues," Tim A. Ahles, PhD, of Memorial Sloan-Kettering Cancer Center in New York, told MedPage Today. "The results indicate that only a subgroup of patients have long-term cognitive changes. Factors associated with long-term changes have been an area of interest to us and others.
"The second issue is that 20% to 30% of breast cancer patients appear to have lower-than-expected cognitive performance at diagnosis. This is higher than in the general population. We were curious to see whether that also predicted post-treatment cognitive changes, and our assessment of cognitive reserve sort of captures that."
An exploratory analysis suggested that tamoxifen negatively affected certain aspects of cognitive function in patients who did not receive chemotherapy.
Cross-sectional and longitudinal studies have yielded evidence that breast cancer chemotherapy causes changes in cognitive function in a subgroup of patients. Similar studies have indicated that tamoxifen also contributes to cognitive decline, Ahles and colleagues wrote in the introduction to their findings.
Other data have shown lower-than-expected performance on neuropsychological tests in subgroups of breast cancer patients before treatment, suggesting that certain aspects of the cancer itself may affect cognitive function.
"Taken together, these findings suggest that there are multiple aspects of breast cancer and its treatment that may impact cognitive functioning in a subgroup of vulnerable individuals, which highlights the importance of identifying risk factors for cognitive decline," the authors wrote.
Age has a well-established influence on cognitive decline, leading to speculation that older adults may have increased vulnerability to cognitive adverse effects of chemotherapy. However, prior studies have not examined possible interactions between age and cancer treatment and resulting effects on cognitive functioning.
Cognitive reserve, which constitutes an individual's innate and developed cognitive capacity, may also play a role in a patient's vulnerability to the cognitive effects of chemotherapy. Ahles and colleagues examined associations among age, pretreatment cognitive reserve, and post-treatment cognitive function. They defined cognitive reserve by scores on the Wide Range Achievement Test (WRAT-3).
The study involved patients with newly diagnosed breast cancer of stages 0 to 3A. The study population included 60 patients who received adjuvant chemotherapy and 72 patients who received adjuvant tamoxifen but no chemotherapy. The control group consisted of 45 healthy women who met inclusion criteria except for a diagnosis of breast cancer.
All study participants completed a battery of tests that assessed verbal ability, verbal memory, visual memory, working memory, processing speed, sorting, distractibility, reaction time, and self-reported depression. Breast cancer patients completed the tests before treatment and at three intervals after completing therapy. Women in the control group were tested on four occasions that approximated the time intervals for the patients.
The analysis showed significant interaction among group, age, and baseline WRAT-3 reading score (P<0.001). Older patients with lower baseline WRAT-3 scores and exposure to chemotherapy scored significantly lower on processing speed, averaging 0.15 less per 10-year increase in age and one standard deviation lower WRAT-3 score than the no-chemotherapy group and 0.23 less than the control group.
The authors found a significant group-by-time interaction (P=0.01) and a significant age-by-WRAT 3 interaction for verbal ability but not a significant three-way interaction.
Age significantly affected performance on the verbal memory, visual memory, working memory, and sorting assessments, and baseline WRAT-3 reading significantly influenced distractibility.
To examine the impact of tamoxifen, the authors compared results of 39 patients treated with the drug, 20 patients who received no endocrine therapy, and the healthy controls. The analysis showed a significant impact of tamoxifen on processing speed (P=0.036) and verbal memory (P=0.05).
Patients treated with tamoxifen performed significantly worse than the controls on processing speed (P=0.016), verbal memory (P=0.018), and verbal ability (P=0.023). Patients who did not receive tamoxifen did not differ significantly from the controls in any of the analyses.
The authors declared they had no relevant disclosures.
Zalman S. Agus, MD Emeritus Professor
University of Pennsylvania School of Medicine and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner