Cancer-related Cognitive Dysfunction Research Articles

Remote, Computerised Cognitive Assessment for Breast Cancer- and Treatment-Related Cognitive Dysfunction: Psychometric Characteristics of the Cogsuite Neurocognitive Battery.

Cancer-related cognitive dysfunction (CRCD) is a significant concern for breast cancer survivors. The Cogsuite battery was developed to improve sensitivity to CRCD with the use of cognitive experimental measures, clarify specific cognitive processes impacted and to be capable of being administered either in-office or remotely. In sum, 357 breast cancer survivors and non-cancer controls completed the Cogsuite Battery in-office (n = 76) or remotely (n = 281). Measure validity, sensitivity to demographic factors, correlations with standard neuropsychological measures and intercorrelations of Cogsuite variables were assessed. Test-retest reliability was evaluated in-office (n = 24) and remotely (n = 80). Test-retest reliability for most variables assessed was adequate to strong. Internal validity, as indicated by the confirmation of expected condition effects within each measure, was established for all measures. Assessment of external validity found age, but not education, was a significant predictor in the majority of measures. Assessment of criterion validity found that Cogsuite variables were correlated with standard measures in psychomotor speed, working memory and executive function, but not associated with self-reported cognition or mood. Cogsuite is reliable and valid, and is sensitive to the effects of increasing age on cognition. The addition of the Cogsuite battery to standard assessment may improve sensitivity to CRCD and identify underlying processes that may be affected. Remote use of the Cogsuite battery in appropriate settings will lessen the burden for providers, researchers and survivors in research and clinical contexts.

Novel computerized neurocognitive test battery is sensitive to cancer-related cognitive deficits in survivors.

There is increasing interest in developing new methods to improve sensitivity in detecting subtle cognitive deficits associated with cancer and its treatments. The current study aimed to evaluate the ability of a novel computerized battery of cognitive neuroscience-based tests to discriminate between cognitive performance in breast cancer survivors and controls. Breast cancer survivors (N = 174) and age-matched non-cancer controls (N = 183) completed the Enformia Cogsuite Battery of cognitive assessments, comprised of 7 computerized tests of multiple cognitive domains. Primary outcome measures included accuracy, reaction times (RT), and coefficients of variation (CV) for each task, as well as global scores of accuracy, RT, and CV aggregated across tests. Linear regressions adjusting for age, education, and remote vs. in-office administration showed that compared to non-cancer controls, survivors had significantly lower performance on measures of attention, executive function, working memory, verbal ability, visuospatial ability, and motor function. Survivors had significantly greater CV on measures of attention, working memory, and processing speed, and significantly slower RT on measures of verbal fluency. The Cogsuite battery demonstrates sensitivity to cancer-related cognitive dysfunction across multiple domains, and is capable of identifying specific cognitive processes that may be affected in survivors. The sensitivity of these tasks to subtle cognitive deficits has advantages for initial diagnosis of cancer-related cognitive dysfunction, as well as detecting changes in survivors' cognitive function over time. The remote delivery of the battery may help overcome barriers associated with in-office administration and increase access to neurocognitive evaluation.

Improving Cognitive Function of Older Adults With a History of Cancer Using Nonpharmacologic Interventions: A Systematic Review

Background: Cancer-related cognitive dysfunction (CRCD) refers to changes in cognitive functioning that occurs as a result of cancer treatment including radiation, hormone therapy, surgery, and most often, chemotherapy. While various nonpharmacologic interventions for cognitive impairments have been studied in younger adults with a history of cancer and in older adult populations without cancer, limited information is available regarding nonpharmacologic interventions for older adults with a history of cancer. Purpose: The purpose of this systematic review is to describe the current nonpharmacologic interventions for older adults with CRCD. Data Sources: PubMed, MEDLINE, CINAHL, and Embase. Study Selection: Articles meeting inclusion criteria were appraised by 2 reviewers independently. The Cochrane Risk of Bias Assessment was used to assess study quality. Data Extraction: The search located 3441 articles; 4 met inclusion criteria. Data Synthesis: Nonpharmacologic interventions addressed the cognitive processes of executive function (n = 2), attention (n = 1), learning/memory (n = 2), perceptual-motor (n = 1), and global cognitive function (n = 3). Two studies used exercise-based interventions and 2 employed cognitive training interventions to address CRCD. Discussion and Limitations: Although improvements in CRCD were found, the interventions used and measure type suggested a high degree of variability challenging the ability to make recommendations for the use of these nonpharmacologic interventions without completion of further studies. Conclusions: As promising evidence has been reported of the effect of aerobic exercise and cognitive training interventions on CRCD in both young survivors of cancer and older adults without cancer, further study is needed to replicate those benefits in older adults with CRCD.

Assessment and Management of Cognitive Function in Patients with Prostate Cancer Treated with Second-Generation Androgen Receptor Pathway Inhibitors.

Preservation of cognitive function is an important outcome in oncology. Optimal patient management requires an understanding of cognitive effects of the disease and its treatment and an efficacious approach to assessment and management of cognitive dysfunction, including selection of treatments to minimize the risk of cognitive impairment. Awareness is increasing of the potentially detrimental effects of cancer-related cognitive dysfunction on functional independence and quality of life. Prostate cancer occurs most often in older men, who are more likely to develop cognitive dysfunction than younger individuals; this population may be particularly vulnerable to treatment-related cognitive disorders. Prompt identification of treatment-induced cognitive dysfunction is a crucial aspect of effective cancer management. We review the potential etiologies of cognitive decline in patients with prostate cancer, including the potential role of androgen receptor pathway inhibitors; commonly used tools for assessing cognitive function validated in metastatic castration-resistant prostate cancer and adopted in non-metastatic castration-resistant prostate cancer trials; and strategies for management of cognitive symptoms. Many methods are currently used to assess cognitive function. The prevalence and severity of cognitive dysfunction vary according to the instruments and criteria applied. Consensus on the definition of cognitive dysfunction and on the most appropriate approaches to quantify its extent and progression in patients treated for prostate cancer is lacking. Evidence-based guidance on the appropriate tools and time to assess cognitive function in patients with prostate cancer is required.

Cognitive Dysfunction: Feasibility of a Brief Intervention to Help Breast Cancer Survivors.

Many cancer survivors experience cancer-related cognitive dysfunction (CRCD), which is believed to be the result of multiple contributing biologic, situational, and personal factors. Efficacious, clinically implementable interventions addressing the multifactorial nature of CRCD are needed. This study evaluated the feasibility of an intervention to help breast cancer survivors mitigate the effects of modifiable factors that contribute to CRCD and improve cognitive functioning. A single-group pre-/post-test design was used. Treatment fidelity was tracked to evaluate implementability; attendance rates, experience surveys, and homework engagement were used to characterize acceptability. Pre- and post-test cognitive functioning, stress, fatigue, and mood were measured to evaluate preliminary efficacy. The intervention was implementable and acceptable to participants. Participants made statistically significant improvements.

Unravelling the Mechanisms of Cancer-Related Cognitive Dysfunction in Non–Central Nervous System Cancer

Unravelling the Mechanisms of Cancer-Related Cognitive Dysfunction in Non–Central Nervous System Cancer

Risk of Cognitive Effects in Comorbid Patients With Prostate Cancer Treated With Androgen Receptor Inhibitors.

Prostate cancer (PC) is primarily a disease of older men. As the risk of neurocognitive decline increases as people age, cognitive dysfunction is a potential complication in men with PC, imposing detrimental effects on functional independence and quality of life. Importantly, risk of cognitive decline may increase with exposure to androgen deprivation therapy and other hormonal therapies. Particular consideration should be given to patients with castration-resistant PC (CRPC), many of whom require continuous, long-term androgen deprivation therapy combined with a second-generation androgen receptor inhibitor. Non-comparative evidence from interventional trials of androgen receptor inhibitors in men with non-metastatic CRPC suggests differential effects on cognitive function and central nervous system-related adverse events within this drug class. Drug-drug interactions with concomitant medications for chronic, non-malignant comorbidities differ among ARIs and thus may contribute further to cognitive impairment. Hence, establishing baseline cognitive function is a prerequisite to identifying subsequent clinical decline associated with androgen receptor-targeted therapies. Although brief, sensitive screening tools for cancer-related cognitive dysfunction are lacking, mental status can be ascertained from the initial medical history and neurocognitive examination, progressing to more in-depth evaluation when impairment is suspected. On-treatment neurocognitive monitoring should be integrated into regular clinical follow-up to preserve cognitive function and quality of life throughout disease management. This review summarizes the multiple factors that may contribute to cognitive decline in men with CRPC, awareness of which will assist clinicians to optimize individual treatment. Practical, clinic-based strategies for managing the risks for and symptoms of cognitive dysfunction are also discussed.

Prospective evaluation of functional brain activity and oxidative damage in breast cancer: changes in task-induced deactivation during a working memory task.

Cancer-related cognitive dysfunction is an important issue for breast cancer survivors. Previous research has identified both cross-sectional and longitudinal alterations in brain function related to cancer status and treatment. In this study, we prospectively collected functional magnetic resonance imaging data in breast cancer cases treated with adjuvant chemotherapy and in controls with no cancer history during a working memory task. Data and blood specimens were collected immediately prior to the start of treatment (baseline) and following completion of treatment (follow-up), and at yoked intervals for controls. In secondary analysis we assessed the levels of oxidative DNA damage in peripheral blood lymphocytes of cases and controls using the Comet assay. A significant group*time interaction revealed reduced deactivation in the superior frontal gyrus in the controls at follow-up, in contrast to cases, who exhibited similar magnitude of deactivation at baseline and follow-up. Working memory performance indicated a significant improvement in the controls at follow-up, and no change in performance in cases. In secondary analyses, oxidative DNA damage levels were elevated in the cases at follow-up compared to controls, but no associations were found between the Comet assay variables and functional imaging at either time-point or group. In light of previous reports on task induced deactivations, our findings reflect continuing effortful processing at follow-up in the breast cancer group, with relatively less effortful processing in the control group given the reduced novelty and practice effects from the baseline to follow-up.

The Development and Evaluation of a Patient Educational Resource for Cancer-Related Cognitive Dysfunction.

Cancer patients and survivors frequently experience cognitive deficits, including problems with attention and memory. These symptoms, referred to as cancer-related cognitive dysfunction (CRCD), are associated with distress. Learning about CRCD and self-management strategies may improve functioning and quality of life in cancer survivors. This study describes the development and evaluation of a CRCD resource for cancer patients. An educational booklet was developed in accordance with multiple evidence-based guidelines for cancer patient education. Cancer patients on chemotherapy (N = 113; 34% men; median age 55, range 19-85) reviewed the booklet and self-reported CRCD knowledge before and after reading the booklet. They also gave ratings on general impressions of the booklet. Seventy-five percent of participants reported that the resource increased their self-reported CRCD knowledge. A Wilcoxon signed-rank test demonstrated that exposure to the booklet elicited a statistically significant change in self-reported knowledge (Z = - 7.13, p < 0.001). A repeated-measures ANCOVA determined that the means of self-reported CRCD knowledge were significantly different between pre- and post-exposure (F(1, 92) = 7.96, p = 0.006, η2 = 0.08). Exploratory analyses revealed that self-reported CRCD knowledge increased across all educational attainment levels from pre- to post-exposure. Ninety-one percent of participants reported that all patients undergoing cancer treatment would find this booklet helpful. Cancer patients at risk for cognitive challenges gained self-reported CRCD knowledge from the booklet, and they think this knowledge would be helpful to others. A resource that makes CRCD understandable and manageable can bridge the gap in self-rated knowledge across education levels.

Impact of transcranial direct current stimulation on sustained attention in breast cancer survivors: Evidence for feasibility, tolerability, and initial efficacy

BackgroundA significant subset of breast cancer survivors experience cognitive difficulties in attention and memory, which persist for years following treatment. Transcranial direct current stimulation (tDCS) has been shown to be effective in improving working memory, attention, processing speed, and other cognitive functions in both healthy and clinical populations. To date, no studies have examined tDCS for rehabilitation of cancer-related cognitive dysfunction. Objective/hypothesisWe aimed to provide preliminary evidence for feasibility, tolerability, acceptability, and efficacy of tDCS in improving performance on a measure of sustained attention. MethodsIn a within-subjects design, 16 breast cancer survivors underwent 2 consecutive days of active tDCS over the prefrontal cortex, and 2 days of sham tDCS, counterbalanced for order of stimulation condition, while performing a continuous performance test. ResultsStimulation was feasible and tolerable, with 89% of participants completing all sessions, and none reporting more than mild to moderate discomfort. Analyses of efficacy showed that during active stimulation, participants had significantly lower standard errors of reaction times overall, indicating better sustained attention ability, as compared to sham stimulation (p < 0.05). Furthermore, the effect of stimulation on standard errors of reaction times differed by inter-stimulus interval (ISI): for 1 and 2 s ISIs, there was no significant difference in performance between sham and active tDCS conditions, but for 4 s ISIs, stimulation improved variability in response times relative to sham (p < 0.05). ConclusionsResults suggest that tDCS is feasible, tolerable, and may be an effective intervention to improve sustained attention difficulties in survivors with cancer-related cognitive dysfunction.

Cognitive rehabilitation for cancer-related cognitive dysfunction: a systematic review.

Individuals with non-central nervous system (CNS) cancers can experience cancer-related cognitive dysfunction (CRCD), negatively impacting daily functioning and quality of life. This systematic review examined cognitive rehabilitation programs aimed at improving cognitive function. PsychInfo and PubMed were searched in February 2019. Eligible studies evaluated a cognitive rehabilitation program for adults with non-CNS cancers and included at least one objective cognitive measure. Across studies, we assessed methodological quality using relevant criteria based on published intervention-related review guidelines and examined findings from performance-based and self-reported outcome measures. 19 studies met inclusion criteria, totalling 1124 participants altogether. These studies included randomized controlled trials (n = 12), partial, quasi or non-randomized controlled trials (n = 3) and single-arm pilot studies (n = 4). All studies found improvements on at least one cognitive measure (performance-based or self-reported). By cognitive domain, objective improvements in memory were most commonly reported, followed by executive functions and processing speed. In terms of methodological quality, studies generally provided clear descriptions of participants and interventions. However, limitations included lack of standardized terminology for interventions, discrepancies in outcome measures, and incomplete statistical reporting. The available evidence supports clinical implementation of cognitive rehabilitation to improve CRCD, with further work in program development, dissemination, and feasibility recommended. We provide specific recommendations to facilitate future research and integration in this field.

Abstract PD6-01: Prevalence and predictors of self-reported memory ability in a large sample of breast cancer survivors

Abstract Background: A substantial subset of women previously treated for breast cancer report deficits in cognitive abilities such as memory. Cancer-related cognitive dysfunction (CRCD) has been linked to a variety of factors including chemotherapy. However, the reported prevalence of symptoms is variable and investigations of CRCD correlates in large samples are limited. This study aimed to 1) investigate whether the prevalence of patient-reported memory problems differs as a function of having received chemotherapy and time-since-treatment; and 2) identify additional factors associated with patient-reported memory in a large sample of breast cancer survivors. Method: In this cross-sectional cohort study, self-administered questionnaires including those assessing memory (Multifactorial Memory Questionnaire) and lifestyle behaviors were mailed to 1500 disease-free breast cancer survivors from three time-since-treatment cohorts (early: 6-18 months, middle: 2-4 years, or late: 5-12 years post-treatment). Demographic and clinical information was collected and confirmed from chart review. The prevalence of clinically significant memory dysfunction was estimated using published normative cut-off scores. We tested whether chemotherapy and time-since-treatment affected memory (analysis of variance), or increased the risk of significant memory dysfunction (odds ratio chi-squared test). Using a forward stepwise regression model, we explored whether patient characteristics (age, education, comorbidities, concussion history, adverse life events), type of treatment (chemotherapy, radiotherapy, hormonal therapy), or lifestyle behaviors (adherence to a Mediterranean diet, physical activity, sleep efficiency, stress management practices) were associated with patient-reported memory. Results: 773 questionnaire packages were returned (mean age=60.4±11.7). 436 (56%) survivors had received chemotherapy (Ch+), and 337 (44%) had not (Ch-). 314 (41%) were early survivors, 244 (32%) were middle, and 215 (28%) were late. Ch+ reported poorer memory than Ch- (F(1, 764)=12.752, p&amp;lt;0.001), with no effect of time-since-treatment or interaction. Prevalence of significant memory dysfunction was higher in Ch+ (28%) than in Ch- (15%) (OR=2.130, 95% CI 1.479-3.066). Younger age and history of concussion were significantly associated with worse patient-reported memory (p=0.002, p&amp;lt;0.001). Unlike chemotherapy (p=0.018), neither radiation nor hormonal treatment was a significant predictor of memory symptoms. Increased physical activity (p=0.002) and higher sleep efficiency (p&amp;lt;0.001) were associated with better memory. Survivors reporting greater memory symptoms also reported greater use of stress management techniques (p=0.026). Conclusion: This large study indicates that chemotherapy doubles the risk of memory symptoms up to at least 10 years post-treatment. Results also point to sleep hygiene and physical activity as potentially meaningful targets for self-management training to reduce CRCD in breast cancer survivors. Citation Format: Bernstein LJ, D'Amico DN, Richard NM, McCready DR, Howell D, Jones JM, Edelstein K. Prevalence and predictors of self-reported memory ability in a large sample of breast cancer survivors [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD6-01.

Chemotherapy-related cognitive impairment: mechanisms, clinical features and research perspectives.

The term chemotherapy-related cognitive impairment (CRCI), or cognitive dysfunction, or chemo fog, or chemo brain, is referred to a decline in a variety of neuropsychological tasks after chemotherapy, or following other anticancer treatments such as radiation therapy or surgery, in patients with non-central nervous system cancers. Furthermore, several pieces of evidence suggest that clinical manifestations of cognitive impairment may occur in cancer patients, prior to chemotherapy or in those not treated with cancer therapies. In these circumstances, it should be more appropriate to use the term cancer-related cognitive dysfunction. Because there is no consensus about its definition and diagnostic criteria, no specific test for CRCI diagnose exists. Whatever the cause, this manifestation of central nervous system toxicity is of increasing concern as the survival rates for cancer have improved steadily and, in turn, cognitive dysfunction can negatively impact the patients and cancer survivors' quality of life. The aim of this work is to offer an overview of the topic and recommendations for future research.

A brief psychoeducational intervention improves memory contentment in breast cancer survivors with cognitive concerns: results of a single-arm prospective study.

One in three breast cancer survivors experiences persistent cognitive changes that can negatively impact daily functioning and quality of life. In our cancer center, the largest tertiary cancer center in Canada, patients with self-reported cancer-related cognitive dysfunction (CRCD) are offered psychoeducation intended to reduce distress about CRCD symptoms and improve everyday cognitive performance, but evidence regarding this intervention's impact is lacking. Here, we assess whether a 1-hour (h), individual psychoeducational intervention designed to promote self-management of CRCD symptoms can improve attitudes and coping with memory-related difficulties in women with breast cancer. Breast cancer survivors with self-reported CRCD (N = 100) were assessed immediately before, immediately after, and 6weeks following the intervention. Participants' memory contentment, knowledge of CRCD, symptom distress, and self-efficacy to cope with symptoms were measured. Participants showed improvements in memory contentment immediately after the intervention (Cohen's d effect size and 95% CI = 0.87 [0.58, 1.16]) and 6weeks later (d = 0.77 [0.48, 1.05]). Significant improvements in secondary study outcomes, including knowledge of CRCD (d = 1.32 [1.01, 1.63]), symptom distress (d = - 0.82 [- 1.11, - 0.53]), and self-efficacy to cope with cognitive symptoms (d = 1.45 [1.14, 1.76]), were also observed. A single, 1-hour psychoeducational intervention can achieve lasting and improved adjustment to memory symptoms in breast cancer survivors with self-reported CRCD. Further investigation using a randomized controlled study design is warranted. Comparisons with previously reported psychoeducational interventions for CRCD are made, and next steps for this research are discussed.

Evaluation of a group psychoeducational intervention for cancer-related cognitive dysfunction in community-dwelling breast cancer survivors.

Background: Cancer-related cognitive dysfunction (CRCD) refers to cognitive difficulties experienced by patients following cancer or its treatment. This study reports on a newly developed psychoeducational intervention intended to help breast cancer survivors manage CRCD symptoms. Objective: We conducted a pilot study to examine preliminary efficacy of this intervention and consider implementation challenges. Methods: Breast cancer survivors reporting cognitive difficulties were assessed before, immediately after, and one-month following the intervention. Primary outcome measures were participant-reported cognitive function and quality of life. Secondary outcome measures included knowledge of CRCD, memory systems and strategies, and healthy lifestyle activities. Follow-up interviews were conducted. Results: Five of the seven women who enrolled completed the intervention and three women returned for the one-month post-intervention testing. Immediately post-intervention, participants showed increased confidence in memory abilities, improved functional abilities, and increased CRCD knowledge. Qualitative analyses revealed four themes underscoring participant’s experience with this intervention: intentional behavioral changes, normalization and validation, changed relationship to self and others, and perceived lack of support from the medical community. Conclusion: This pilot study suggests this intervention benefits survivors in multiple ways. A randomized controlled design with a larger sample size is needed to replicate and understand the reliability of changes over time.

Mechanisms and Treatment of Chemotherapy-Induced Cognitive Impairment ('Chemobrain')

Chemotherapy-induced cognitive impairment (CICI; also called “cancer-related cognitive impairment,” “cancer-related cognitive dysfunction,” or “chemobrain”) is a widely recognized consequence of cancer treatment, with potential to disrupt the daily and occupational lives of survivors for a period of time. This review covers what has been published on the mechanisms involved in, and treatment approaches explored to date for, CICI.

Initial Study on Cancer-Related Cognitive Dysfunction With the Implementation of QEEG

Abstract Chemotherapy is one of the most common treatments used in cancer therapy despite its serious side effects, which remain a huge concern. To the most common side effects (apart from weight and hair loss) include memory and concentration problems as well as changes in taste. This paper presents a very preliminary study (with only one elderly female subject participating) focusing on cognitive dysfunction after chemotherapy in breast cancer. This phenomenon, called Cancer-Related Cognitive Dysfunction (CRCD), is a frequent occurrence. The obtained results prove the impact of chemotherapy on the participant’s ability to concentrate. The QEEG method and digital data analysis were used as the measurement methods.

Focus Forward: Outcomes of a Brief Occupational Therapy Intervention for Cancer-Related Cognitive Dysfunction

Abstract Date Presented 3/30/2017 Results of this pilot and feasibility study indicate that women with breast cancer who received a brief occupational therapy intervention for cancer-related cognitive dysfunction experienced pre–post improvements in self-reported cognition and occupational functioning. Primary Author and Speaker: Shayne Hopkins Contributing Authors: Mary Vining Radomski, Marsha Finkelstein, Mattie Anheluk, Kristin Berling, Michele Darger, Kim Grabe, M. Tracy Morrison, Joette Zola, Nancy Hutchison

Cognitive behavioral therapy for cancer-related cognitive dysfunction.

To provide the reader with an overview of the cognitive-behavioral conceptualization of cancer-related cognitive dysfunction (CRCD) and how cognitive behavioral therapy (CBT) can play an important role in treatment. Recent findings show that Memory and Attention Adaptation Training (MAAT), a CBT developed to help cancer survivors develop adaptive skills to improve daily cognitive performance and emotional coping, may be an efficacious treatment of CRCD and can be delivered through videoconference technology to improve survivor access to care. The etiology of CRCD remains largely undetermined and likely is produced by multiple mechanisms. This can include neuronal death, microvascular damage, inflammatory processes, and psychological factors of perceptions of inadequate cognitive capacity to meet performance demands and related emotional distress. As a result, there are a variety of treatments currently being researched. More research with larger sample sizes, multiple clinicians and multiple sites are needed to confirm efficacy, but CBT approaches such as Memory and Attention Adaptation Training that address multiple psychological factors involved may offer a flexible nonpharmacological approach to CRCD that optimizes quality of life outcomes.

An exploratory study of host polymorphisms in genes that clinically characterize breast cancer tumors and pretreatment cognitive performance in breast cancer survivors.

PurposeInspired by the hypothesis that heterogeneity in the biology of breast cancers at the cellular level may account for cognitive dysfunction symptom variability in survivors, the current study explored relationships between host single-nucleotide polymorphisms (SNPs) in 25 breast cancer-related candidate genes (AURKA, BAG1, BCL2, BIRC5, CCNB1, CD68, CENPA, CMC2, CTSL2, DIAPH3, ERBB2, ESR1, GRB7, GSTM1, MELK, MKI67, MMP11, MYBL2, NDC80, ORC6, PGR, RACGAP1, RFC4, RRM2, and SCUBE2), identified from clinically relevant prognostic multigene-expression profiles for breast cancer, and pretreatment cognitive performance.Patients and methodsThe sample (n=220) was comprised of 138 postmenopausal women newly diagnosed with early stage breast cancer and 82 postmenopausal age- and education-matched healthy controls without breast cancer. Cognitive performance was assessed after primary surgery but prior to initiation of adjuvant chemotherapy and/or hormonal therapy using a comprehensive battery of neuropsychological tests encompassing eight cognitive function composite domains: attention, concentration, executive function, mental flexibility, psychomotor speed, verbal memory, visual memory, and visual working memory. In total, 131 SNPs were included in the analysis. Standard and robust multiple linear regression modeling was used to examine relationships between each domain and the presence or absence of one or more minor alleles for each SNP. Genetic risk/protection scores (GRSs) were calculated for each domain to evaluate the collective effect of possession of multiple risk/protective alleles.ResultsWith the exception of CMC2, MMP11, and RACGAP1, significant (P<0.05) SNP main effect and/or SNP by future prescribed treatment group interactions were observed for every gene between at least one domain and one or more SNPs. All GRSs were found to be significantly (P<0.001) associated with each respective domain score.ConclusionAssociations between host SNPs and computed GRSs and variability in pretreatment cognitive function performance support the study hypothesis, and warrant further investigations to identify biomarkers for breast cancer-related cognitive dysfunction.