Cognitive Complaints After Breast Cancer Treatments
Cognitive Complaints After Breast Cancer Treatments
Background Cognitive complaints are reported frequently after breast cancer treatments. Their association with neuropsychological (NP) test performance is not well-established.
Methods Early-stage, posttreatment breast cancer patients were enrolled in a prospective, longitudinal, cohort study prior to starting endocrine therapy. Evaluation included an NP test battery and self-report questionnaires assessing symptoms, including cognitive complaints. Multivariable regression models assessed associations among cognitive complaints, mood, treatment exposures, and NP test performance.
Results One hundred eighty-nine breast cancer patients, aged 21–65 years, completed the evaluation; 23.3% endorsed higher memory complaints and 19.0% reported higher executive function complaints (>1 SD above the mean for healthy control sample). Regression modeling demonstrated a statistically significant association of higher memory complaints with combined chemotherapy and radiation treatments (P = .01), poorer NP verbal memory performance (P = .02), and higher depressive symptoms (P < .001), controlling for age and IQ. For executive functioning complaints, multivariable modeling controlling for age, IQ, and other confounds demonstrated statistically significant associations with better NP visual memory performance (P = .03) and higher depressive symptoms (P < .001), whereas combined chemotherapy and radiation treatment (P = .05) approached statistical significance.
Conclusions About one in five post–adjuvant treatment breast cancer patients had elevated memory and/or executive function complaints that were statistically significantly associated with domain-specific NP test performances and depressive symptoms; combined chemotherapy and radiation treatment was also statistically significantly associated with memory complaints. These results and other emerging studies suggest that subjective cognitive complaints in part reflect objective NP performance, although their etiology and biology appear to be multifactorial, motivating further transdisciplinary research.
Cognitive impairment is a feared complication of cancer treatment (1–4) and has been extensively studied in breast cancer patients. Subjective cognitive complaints have been a driving force behind research in this area since the late 1990s. A recent meta-analysis conducted by Jim et al. concluded that in the posttreatment period with standard dose chemotherapy, statistically significant small deficits in neuropsychological (NP) domains of verbal and visuospatial ability could be detected. In most early studies, subjective complaints were more often associated with symptoms of depression and anxiety, calling into question whether patient-reported complaints reflected neurophysiological changes.
Brain imaging studies have begun to provide more information about the biology of cognitive function after cancer treatment exposures. A recent prospective, controlled study (pre- and postchemotherapy) of NP testing and magnetic resonance imaging (MRI) found changes in gray matter associated with chemotherapy treatment, suggesting a physiological basis for cognitive disturbance. Two additional imaging studies demonstrated that chemotherapy-exposed breast cancer patients reported cognitive complaints (memory and executive function) that aligned with relevant NP test domains, as well as with associated anatomic brain regions. These emerging data suggest that cognitive complaints may reflect underlying changes in cerebral functioning. The lack of association between NP test performance and subjective cognitive complaints in prior studies with breast cancer patients could reflect the lack of specificity and sensitivity of the self-report tools, or could be due to reliance on global measures rather than domain-specific assessments.
To this end, we examined the relationship between subjective cognitive complaints and NP functioning in the setting of the University of California, Los Angeles (UCLA) Mind Body Study (MBS), a large prospective cohort study of recently diagnosed, early-stage breast cancer patients enrolled after completion of adjuvant therapy and prior to initiation of endocrine therapy. A principal goal of the MBS was to assess prospectively the impact of endocrine therapy on subsequent cognitive functioning, while accounting for prior hormone exposures and treatment-associated changes in menstrual status. Cognitive complaints are at their peak in the immediate post–adjuvant treatment period, and the MBS baseline assessment provided a rich source of data to examine potential contributing factors. We hypothesized that domain-specific cognitive complaints could be identified in this setting, and that they would be associated with relevant NP domains, as well as with chemotherapy treatment exposure and change in menstrual status.
Abstract and Introduction
Abstract
Background Cognitive complaints are reported frequently after breast cancer treatments. Their association with neuropsychological (NP) test performance is not well-established.
Methods Early-stage, posttreatment breast cancer patients were enrolled in a prospective, longitudinal, cohort study prior to starting endocrine therapy. Evaluation included an NP test battery and self-report questionnaires assessing symptoms, including cognitive complaints. Multivariable regression models assessed associations among cognitive complaints, mood, treatment exposures, and NP test performance.
Results One hundred eighty-nine breast cancer patients, aged 21–65 years, completed the evaluation; 23.3% endorsed higher memory complaints and 19.0% reported higher executive function complaints (>1 SD above the mean for healthy control sample). Regression modeling demonstrated a statistically significant association of higher memory complaints with combined chemotherapy and radiation treatments (P = .01), poorer NP verbal memory performance (P = .02), and higher depressive symptoms (P < .001), controlling for age and IQ. For executive functioning complaints, multivariable modeling controlling for age, IQ, and other confounds demonstrated statistically significant associations with better NP visual memory performance (P = .03) and higher depressive symptoms (P < .001), whereas combined chemotherapy and radiation treatment (P = .05) approached statistical significance.
Conclusions About one in five post–adjuvant treatment breast cancer patients had elevated memory and/or executive function complaints that were statistically significantly associated with domain-specific NP test performances and depressive symptoms; combined chemotherapy and radiation treatment was also statistically significantly associated with memory complaints. These results and other emerging studies suggest that subjective cognitive complaints in part reflect objective NP performance, although their etiology and biology appear to be multifactorial, motivating further transdisciplinary research.
Introduction
Cognitive impairment is a feared complication of cancer treatment (1–4) and has been extensively studied in breast cancer patients. Subjective cognitive complaints have been a driving force behind research in this area since the late 1990s. A recent meta-analysis conducted by Jim et al. concluded that in the posttreatment period with standard dose chemotherapy, statistically significant small deficits in neuropsychological (NP) domains of verbal and visuospatial ability could be detected. In most early studies, subjective complaints were more often associated with symptoms of depression and anxiety, calling into question whether patient-reported complaints reflected neurophysiological changes.
Brain imaging studies have begun to provide more information about the biology of cognitive function after cancer treatment exposures. A recent prospective, controlled study (pre- and postchemotherapy) of NP testing and magnetic resonance imaging (MRI) found changes in gray matter associated with chemotherapy treatment, suggesting a physiological basis for cognitive disturbance. Two additional imaging studies demonstrated that chemotherapy-exposed breast cancer patients reported cognitive complaints (memory and executive function) that aligned with relevant NP test domains, as well as with associated anatomic brain regions. These emerging data suggest that cognitive complaints may reflect underlying changes in cerebral functioning. The lack of association between NP test performance and subjective cognitive complaints in prior studies with breast cancer patients could reflect the lack of specificity and sensitivity of the self-report tools, or could be due to reliance on global measures rather than domain-specific assessments.
To this end, we examined the relationship between subjective cognitive complaints and NP functioning in the setting of the University of California, Los Angeles (UCLA) Mind Body Study (MBS), a large prospective cohort study of recently diagnosed, early-stage breast cancer patients enrolled after completion of adjuvant therapy and prior to initiation of endocrine therapy. A principal goal of the MBS was to assess prospectively the impact of endocrine therapy on subsequent cognitive functioning, while accounting for prior hormone exposures and treatment-associated changes in menstrual status. Cognitive complaints are at their peak in the immediate post–adjuvant treatment period, and the MBS baseline assessment provided a rich source of data to examine potential contributing factors. We hypothesized that domain-specific cognitive complaints could be identified in this setting, and that they would be associated with relevant NP domains, as well as with chemotherapy treatment exposure and change in menstrual status.
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