New findings suggest that self-reported cognitive complaints from breast cancer patients who have received chemotherapy and radiation therapy are associated with neuropsychological test performance, according to a study published in the Journal of the National Cancer Institute (2013:105;791-801).
“People have said they're just depressed and that's why they're having these difficulties,'” said the study's lead author, Patricia A. Ganz, MD, Professor of Health Policy and Management at the Fielding School of Public Health and Professor of Medicine at the David Geffen School of Medicine, both at UCLA, and Director of the Division of Cancer Control Research at UCLA's Jonsson Comprehensive Cancer Center. “Our study shows, though, that independent of depression there are changes in the neuropsychological tests that map onto the self-reported complaints.”
The team's previous research showed that cognitive problems in breast cancer patients may be associated with the level of activity of circulating tumor necrosis factor—a biological explanation for why women do experience cognitive problems post-treatment (OT, 8/10/11 issue). But, this new research is one of the first studies to link subtle abnormalities in those changes with standard neuropsychological test scores, and more specifically in a population of patients who have not yet undergone hormone therapy.
“This paper says we need to believe patients when they're telling us they're having problems,” she said.
In a sample of 189 patients with breast cancer who had received chemotherapy and/or radiation treatment, the researchers found that patients' self-reported memory and executive function complaints, which occurred in about one in five of the patients, were associated with poorer, domain-specific neuropsychological test performances. Patients were enrolled within three months after completing initial treatment, but before the start of endocrine therapy (if planned).
Using the Patient's Assessment of Own Functioning Inventory—which assesses four major domains of cognitive functioning, including memory, higher level learning (planning and organization abilities), language and communication, and motor-sensory perception—the authors first compared self-reported cognitive complaint scores of the patients with breast cancer with those of a healthy population.
Twenty-three percent of the breast cancer survivors had increased memory complaints and 19 percent had increased higher level cognition complaints (executive functioning). Subsequent analyses focused on these two domains to determine what factors were associated with these complaints.
In multivariate models, chemotherapy and radiation together were associated with increased complaints in both domains, Ganz explained. For the self-reported memory problems, poorer performances on neuropsychological tests of verbal memory were significantly associated with self-reported memory complaints and higher depressive symptoms.
For the higher-level cognition domain, greater complaints were associated with better visual memory performance on neuropsychological tests as well as higher depressive symptoms (measured by the Beck Depression Inventory-II). But, Ganz noted, the depressive symptoms scores were in the normal range, and actually reflected self-reported complaints of sleep disturbance, loss of interest in sex, and fatigue—constitutional symptoms, common after adjuvant therapy.
“We're showing here—using standard neuropsychological tests—that there's evidence of abnormality in those who are complaining,” she said.
Other findings, Ganz noted:
* There was no significant relationship between cognitive complaints and recent onset of amenorrhea; and
* For executive functioning, there was an association between complaints and past hormonal therapy, suggesting that this might have influenced the better visual memory performance in these women.
Asked for a comment for this article, Tim Ahles, PhD, a behavioral psychologist who founded and currently leads Memorial Sloan-Kettering Cancer Center's Neurocognitive Research Laboratory, said that the study by Ganz et al focuses on the impact of cognitive problems on a person's ability to function, and shows a clearer correlation than previous research has.
“And, the identification of a self-report instrument that could guide further evaluation and/or referral should be helpful to clinicians to address these issues,” he added, noting that neuropsychological testing is neither feasible nor practical in all community-based practices and care settings.
Forthcoming findings from the research will allow the team to understand how cognitive changes are related to the genetic factors, biomarkers, and outcomes of survivors of breast cancer, he said. “It has become clear that there are multiple aspects of breast cancer treatment—including endocrine therapy—that can affect cognitive functioning. Therefore, this longitudinal data will provide important information about the impact of endocrine therapy and will allow the investigators to examine the potential interactive effects of a history of previous treatments—e.g., chemotherapy, radiation therapy, and others.”
In this paper, cognitive problems in women were analyzed after chemotherapy and radiation, but before the start of endocrine therapy, Ganz explained. All treatment exposures are likely contributing to the complaints, but the goal of this research is to better understand why and understand patients' patterns of recovery.
“Knowing that somebody is more likely to be susceptible to cognitive problems would allow us to target interventions—and we might start interventions earlier to help patients recover—rather than waiting for them to have difficulties,” Ganz said. Studies are currently underway to test pharmaceutical therapies, computer-based memory interventions, and rehab interventions, to help treat patients' cognitive complaints, she said. “But first, understanding the mechanisms is important.”
Another recent paper by Ganz based on other findings from this cohort of patients showed that inflammation is a likely contributor to cognitive problems by identifying an association between pro-inflammatory cytokine levels in the blood and brain metabolism (Brain, Behavior, and Immunity 2013;30:S99-S108). And, another paper suggests that inflammatory processes also contribute to cancer-related fatigue (?JCO 2013;31:1656-1661).
Ganz said that additional data collected from this study after the patients had received endocrine therapy is now being analyzed to better understand the effect of adding that treatment: “We expect that a large number of these patients are going to get better, but we want to understand which patients are at risk for having persistent difficulties.”