Trajectories of Cognitive Function and Associated Phenotypic and Genotypic Factors in Breast Cancer

Abstract

OBJECTIVES This study identified women with unique trajectories of executive function, concentration, and visual working memory before and during adjuvant therapy for breast cancer, and examined phenotypic and genotypic predictors associated with subgroups. SAMPLE & SETTING 399 postmenopausal women, of whom 288 were women with early-stage breast cancer and 111 were women without breast cancer, matched on age and years of education to the women with breast cancer, and all at an urban cancer center. METHODS & VARIABLES A repeated-measures design was used; assessments occurred before adjuvant therapy and every six months post-therapy initiation. Group-based trajectory modeling determined subgroups. Multinomial logistic regression identified phenotypic and genotypic characteristics. RESULTS Three executive function and concentration trajectory subgroups were identified: low, moderate, and high; two visual working memory subgroups were identified: low and high. IMPLICATIONS FOR NURSING Advancing age, greater pretherapy fatigue, and poorer pretherapy cognitive function are associated with the low subgroups. DNA repair and oxidative stress mechanisms may be involved in the cognitive changes that women experience.

Genetic risk factors for cancer-related cognitive impairment: a systematic review

“…Ten studies reported results on the influence of APOE genotypes on cognitive functioning in cancer patients. Six focused on breast cancer (BC) patients [19][20][21][22][23][24], one reported on both BC and lymphoma patients [25], and three reported on other patient groups [26][27][28]. The remaining seven studies reported results from studies investigating other genes than APOE, e.g., COMT [24,29] and BDNF [14,24], with five of these studies focusing on BC patients [14,[29][30][31][32], one on prostate cancer patients [33], and one on patients with mixed non-CNS cancers [34].…”

“…Using the NIH Quality Assessment Tool [18], each study received a quality rating (range: 0-14). Eight studies [14,19,20,23,[25][26][27]33] were rated 'good quality' (>9 criteria met), and the remaining nine studies [21,22,24,[28][29][30][31][32]34] were rated 'fair quality' (5-9 criteria met). Study quality ratings are shown in Supplementary Table S3.…”

“…The three APOE isoforms (e2, e3, e4) are encoded by the genotypic combination of two SNPs (rs429358, rs7412) [35] and studies assessing associations between these and CRCI categorized patients into non-carriers or carriers of at least one e4 allele. Four studies [19,20,25,26] showed that carrying at least one e4 allele was associated with some degree of CRCI, while six studies [21][22][23][24]27,28] found no association. Of the studies finding e4 to be a risk factor for cognitive impairment, three were longitudinal and administered neuropsychological tests before, during and/or after further treatment.…”

“…In general, the largest effects were seen for the interaction effects between e4 carrier ship and treatment with AI and smoking history, respectively. Of the six studies finding no association between APOE genotypes and CRCI, two were longitudinal, investigating BC [23] and colorectal cancer patients [27], respectively (N = 190 and 243, respectively) and only the latter of these reported percentage of e4 allele carriers (23%). Four cross-sectional studies failed to find an association between e4 and cognitive impairment (carriers: 18-23%; average N = 246).…”

“…One cross-sectional [30] and one longitudinal follow-up study [23] investigated associations of four DNA repair genes and five oxidative stress genes, with CRCI in BC patients recruited from the same parent study and scheduled for treatment with AI and/or CT. Neuropsychological test scores were combined into eight cognitive factors. Prior to adjuvant treatment, each cognitive factor was significantly associated with one or more DNA repair or oxidative stress gene SNPs.…”