Does neighborhood socioeconomic status alter memory change associated with a cancer diagnosis? Preliminary evidence from the US Health and Retirement Study.

BACKGROUND: Neighborhood disadvantage has been linked to cognitive impairment, but little is known about the effect of neighborhood disadvantage on long-term cancer-related memory decline. METHODS: Incident cancer diagnosis and memory (immediate and delayed recall, combined with proxy-reported memory) were assessed at biennial interviews in the U.S. Health and Retirement Study (N=13,293, 1998-2016). Neighborhood disadvantage was measured using the National Neighborhood Data Archive disadvantage index, categorized into tertiles (T1: least disadvantaged - T3: most disadvantaged). Linear mixed-effects models estimated the standardized memory trajectories in participants with or without cancer, by neighborhood disadvantage. RESULTS: Living in more disadvantaged neighborhoods was associated with worse mean memory function and steeper memory declines, regardless of cancer status. An incident cancer diagnosis was associated with an acute memory drop for those living in least disadvantaged neighborhoods but not more disadvantaged neighborhoods (T1: -0.05, 95% CI: -0.08, -0.01; T3: -0.13, 95% CI: -0.06, 0.03). Cancer survivors in the least disadvantaged neighborhoods had a slight memory advantage in the years prior to diagnosis (T1: 0.09, 95% CI: 0.04, 0.13) and after diagnosis (T1: 0.07, 95% CI: 0.01, 0.13). CONCLUSIONS: An incident cancer diagnosis among those living in the least disadvantaged neighborhoods was associated with an acute memory drop at the time of diagnosis and a long-term memory advantage before and after diagnosis compared to cancer-free individuals in similar neighborhoods. IMPACT: These findings could inform interventions to promote cancer survivor's long-term aging. Future studies should investigate the social and biological pathways through which nSES could influence cancer-related memory changes.

Breast cancers in monoallelic MUTYH germline mutation carriers have clinicopathological features overlapping with those in BRCA1 germline mutation carriers.

PURPOSE: Breast cancer patients referred to genetic counseling often undergo genetic testing with broad panels that include both breast cancer susceptibility genes as well as genes more specific for extramammary sites. As a result, patients are often incidentally found to have germline mutations in genes that are not necessarily related to breast cancer risk. One such gene is MUTYH. To understand the role MUTYH may play in breast cancer, the clinicopathological features of patients with monoallelic MUTYH germline mutation and breast cancer were examined. METHODS: The clinicopathological characteristics of the breast cancers from patients with monoallelic MUTYH mutation were compared to breast cancer patients with other germline mutations in known breast cancer susceptibility genes, including ATM, BRCA1/2, CHEK2, and PALB2. The breast cancer patients who received genetic counseling but tested negative for the aforementioned gene mutations were used as a control group. RESULTS: Histologic characteristics of the breast cancers arising in monoallelic MUTYH mutation carriers had significantly larger tumor size, higher tumor grade, and more high-risk biomarker profiles (i.e., Her2-positive and triple-negative) than breast cancer patients with susceptibility genes, except for BRCA1. MUTYH mutation carriers also showed a trend of more frequent intratumoral divergency in terms of tumor grade and biomarker profiles. CONCLUSION: Although germline monoallelic MUTYH mutation is not thought to confer a meaningfully increased risk of breast cancer development, it may contribute to pathological aggressiveness and diversity of breast cancers when they sporadically arise in MUTYH carriers.

Education, incident cancer, and rate of memory decline in a national sample of US adults in mid-to-later-life.

INTRODUCTION: Middle-aged and older adults who develop cancer experience memory loss following diagnosis, but memory decline in the years before and after cancer diagnosis is slower compared to their cancer-free counterparts. Educational attainment strongly predicts memory function during aging, but it is unclear whether education protects against memory loss related to cancer incidence or modifies long-term memory trajectories in middle-aged and older cancer survivors. MATERIALS AND METHODS: Data were from 14,449 adults (3,248 with incident cancer, excluding non-melanoma skin cancer) aged 50+ in the population-based US Health and Retirement Study from 1998 to 2016. Memory was assessed every two years as a composite of immediate and delayed word recall tests and proxy assessments for impaired individuals. Memory scores all time points were standardized at to the baseline distribution. Using multivariate-adjusted linear mixed-effects models, we estimated rates of memory decline in the years before cancer diagnosis, shortly after diagnosis, and in the years after diagnosis. We compared rates of memory decline between incident cancer cases and age-matched cancer-free adults, overall and according to level of education (<12 years, "low"; 12 to <16 years, "intermediate"; ≥16 years, "high"). RESULTS: Incident cancer diagnoses were followed by short-term declines in memory averaging 0.06 standard deviation (SD) units (95% confidence interval [CI]: -0.084, -0.036). Those with low education experienced the strongest magnitude of short-term decline in memory after diagnosis (-0.10 SD units, 95% CI: -0.15, -0.05), but this estimate was not statistically significantly different from the short-term decline in memory experienced by those with high education (-0.04 SD units, 95% CI: -0.08, 0.01; p-value for education as an effect modifier = 0.15). In the years prior to and following an incident cancer diagnosis, higher educational attainment was associated with better memory, but it did not modify the difference in rate of long-term memory decline between cancer survivors and those who remained cancer-free. DISCUSSION: Education was associated with better memory function over time among both cancer survivors and cancer-free adults aged 50 and over. Low education may be associated with a stronger short-term decline in memory after a cancer diagnosis.

Functional aging trajectories of older cancer survivors: a latent growth analysis of the US Health and Retirement Study.

PURPOSE: We aimed to identify prototypical functional aging trajectories of US cancer survivors aged 50 and older, overall and stratified by sociodemographic and health-related characteristics. METHODS: Data were from 2986 survivors of a first incident cancer diagnosis (except non-melanoma skin cancer) after age 50 in the population representative U.S. Health and Retirement Study from 1998-2016. Cancer diagnoses, episodic memory function, and activity of daily living (ADL) limitations were assessed at biennial study interviews. Using time of cancer diagnosis as the baseline, we used group-based trajectory modeling to identify trajectories of memory function and ADL limitations following diagnosis. RESULTS: We identified five memory loss trajectories (high: 8.4%; medium-high: 18.3%; medium-low: 21.5%; low: 25.5%; and, very low: 26.2%), and four ADL limitation trajectories (high/increasing limitations: 18.7%; medium limitations: 18.7%; low limitations: 8.14%; no limitations: 60.0). The high memory loss and high/increasing ADL limitation trajectories were both characterized by older age, being female (52% for memory, 58.9% for ADL), having lower pre-cancer memory scores, and a higher prevalence of pre-cancer comorbidities including stroke (30.9% for memory and 29.7% for ADL), hypertension (64.7% for memory and 69.8 for ADL), and depressive symptoms. In joint analyses, we found that generally those with higher memory were more likely to have fewer ADL limitations and vice versa. CONCLUSION: Older cancer survivors experience heterogeneous trajectories of functional aging that are largely characterized by comorbidities prior to diagnosis. IMPLICATION FOR CANCER SURVIVORS: Results can help identify older cancer survivors at increased risk for accelerated functional decline.

HER2-positive/ER-low breast carcinoma shows a response to neoadjuvant chemotherapy similar to that of HER2-positive/ER-negative breast carcinoma.

Negative expression of estrogen receptor (ER) predicts response to chemotherapy in breast cancers (BCs). ER negative cancers are those with less than 1 % of nuclear staining. Tumors with 1-10 % staining are sub-classified as "low-positive" (ER-low). HER2 negative tumors with ER low staining are considered biologically and clinically equivalent to ER negative tumors. This study investigates whether ER low expression in HER2-positive (HER2+) BCs has different clinical behavior than ER negative HER2-positive tumors. We used a sample of 171 patients with HER2+ BCs to compare risk of residual cancer after neoadjuvant chemotherapy by different ER expression strength. Patients were classified into 3 groups: ER-negative (ER <1 %); ER-low (ER <10 %, any intensity or <33 % staining, weak intensity); and ER-high (ER = 10-33 %, moderate to strong intensity or >33 %, any intensity). The risk of residual cancer in patients with ER-low tumors was similar to the risk in patients with ER-negative tumors (RR = 0.76, 95 % CI: 0.30-1.93). Conversely, patients with ER-high tumors had twice the risk of residual cancer than patients with ER-negative tumors (RR = 2.20, 95 % CI: 1.46-3.31). These findings persisted after adjusting for tumor grade, clinical tumor and lymph node stage, chemotherapy regimen, and progesterone receptor status. In this cohort of patients with HER2+ BCs, ER-low tumors had a similar pathologic response to chemotherapy as ER-negative tumors suggesting similar clinical behavior. Future research should address biological explanations to these similarities between ER negative and ER low breast cancers such as HER2 enriched phenomenon.

Does a Cancer Diagnosis in Mid-to-Later Life Modify Racial Disparities in Memory Aging?

BACKGROUND: It is unknown whether an incident cancer diagnosis differentially impacts acute and long-term memory aging between older White and Black Americans. METHODS: Incident cancer diagnoses and memory (immediate and delayed recall, combined with proxy-reported memory) were assessed at biennial study interviews in the US Health and Retirement Study (N=14,235, 1998-2016). We used multivariable segmented linear mixed-effects models to evaluate the rate of change in standardized memory score (SD/decade) in the years before, acutely at the time of, and in the years following an incident cancer diagnosis, compared to cancer-free adults, by race. RESULTS: Black participants experienced faster memory decline than White participants (cancer-free group: -1.211 vs. -1.077; P<0.0001). An incident cancer diagnosis was associated with an acute memory drop in White, but not Black participants (-0.065 vs. 0.024; P<0.0001). However, White cancer survivors experienced slower memory decline than cancer-free White adults before and after diagnosis, but this memory advantage was not observed among Black cancer survivors. CONCLUSIONS: Racial disparities in memory aging are not modified by an incident cancer diagnosis. The acute cancer-related memory decline and long-term memory advantage experienced by White, but not Black, cancer survivors relative to cancer-free older adults, requires further investigation.

The Association Between Cancer and Spousal Rate of Memory Decline: A Negative Control Study to Evaluate (Unmeasured) Social Confounding of the Cancer-memory Relationship.

Cancer diagnoses are associated with better long-term memory in older adults, possibly reflecting a range of social confounders that increase cancer risk but improve memory. We used spouse's memory as a negative control outcome to evaluate this possible confounding, since spouses share social characteristics and environments, and individuals' cancers are unlikely to cause better memory among their spouses. We estimated the association of an individual's incident cancer diagnosis (exposure) with their own (primary outcome) and their spouse's (negative control outcome) memory decline in 3601 couples from 1998 to 2014 in the Health and Retirement Study, using linear mixed-effects models. Incident cancer predicted better long-term memory for the diagnosed individual. We observed no association between an individual's cancer diagnosis and rate of spousal memory decline. This negative control study suggests that the inverse association between incident cancer and rate of memory decline is unlikely to be attributable to social/behavioral factors shared between spouses.

Association Between Alzheimer Disease and Cancer With Evaluation of Study Biases: A Systematic Review and Meta-analysis.

Importance: Observational studies consistently report inverse associations between cancer and Alzheimer disease (AD). Shared inverse etiological mechanisms might explain this phenomenon, but a systematic evaluation of methodological biases in existing studies is needed. Objectives: To systematically review and meta-analyze evidence on the association between cancer and subsequent AD, systematically identify potential methodological biases in studies, and estimate the influence of these biases on the estimated pooled association between cancer and AD. Data Sources: All-language publications were identified from PubMed, Embase, and PsycINFO databases through September 2, 2020. Study Selection: Longitudinal cohort studies and case-control studies on the risk of AD in older adults with a history of any cancer type, prostate cancer, breast cancer, colorectal cancer, or nonmelanoma skin cancer, relative to those with no cancer history. Data Extraction and Synthesis: Two reviewers independently abstracted the data and evaluated study biases related to confounding, diagnostic bias, competing risks, or survival bias. Random-effects meta-analysis was used to provide pooled estimates of the association between cancer and AD. Metaregressions were used to evaluate whether the observed pooled estimate could be attributable to each bias. The study was designed and conducted according to the Preferring Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Main Outcomes and Measures: Incidence, hazard, or odds ratios for AD comparing older adults with vs without a previous cancer diagnosis. Results: In total, 19 cohort studies and 3 case-control studies of the associations between any cancer type (n = 13), prostate cancer (n = 5), breast cancer (n = 1), and nonmelanoma skin cancer (n = 3) with AD were identified, representing 9 630 435 individuals. In all studies combined, cancer was associated with decreased AD incidence (cohort studies: random-effects hazard ratio, 0.89; 95% CI, 0.79-1.00; case-control studies: random-effects odds ratio, 0.75; 95% CI, 0.61-0.93). Studies with insufficient or inappropriate confounder control or greater likelihood of AD diagnostic bias had mean hazard ratios closer to the null value, indicating that these biases could not explain the observed inverse association. Competing risks bias was rare. Studies with greater likelihood of survival bias had mean hazard ratios farther from the null value. Conclusions and Relevance: The weak inverse association between cancer and AD may reflect shared inverse etiological mechanisms or survival bias but is not likely attributable to diagnostic bias, competing risks bias, or insufficient or inappropriate control for potential confounding factors.

The competing risk of death and selective survival cannot fully explain the inverse cancer-dementia association.

INTRODUCTION: We evaluated whether competing risk of death or selective survival could explain the reported inverse association between cancer history and dementia incidence (incidence rate ratio [IRR] ≈ 0.62-0.85). METHODS: A multistate simulation model of a cancer- and dementia-free cohort of 65-year-olds was parameterized with real-world data (cancer and dementia incidence, mortality), assuming no effect of cancer on dementia (true IRR = 1.00). To introduce competing risk of death, cancer history increased mortality. To introduce selective survival, we included a factor (prevalence ranging from 10% to 50%) that reduced cancer mortality and dementia incidence (IRRs ranged from 0.30 to 0.90). We calculated IRRs for cancer history on dementia incidence in the simulated cohorts. RESULTS: Competing risk of death yielded unbiased cancer-dementia IRRs. With selective survival, bias was small (IRRs = 0.89 to 0.99), even under extreme scenarios. DISCUSSION: The bias induced by selective survival in simulations was too small to explain the observed inverse cancer-dementia link, suggesting other mechanisms drive this association.

Rate of Memory Change Before and After Cancer Diagnosis.

Importance: Patients with a history of cancer, even nonfatal cancers, have lower subsequent Alzheimer disease incidence. An inverse biological link between carcinogenesis and neurodegeneration has been hypothesized, although survival and detection biases are possible explanations. Objective: To compare long-term memory trajectories before and after incident cancer with memory trajectories of similarly aged individuals not diagnosed with cancer. Design, Setting, and Participants: This population-based cohort study included 14 583 US adults born before 1949 with no cancer history from the Health and Retirement Study. Biennial assessments were performed for up to 16 years from 1998 to 2014. Data analysis was performed from January 8 to October 5, 2018. Exposures: Self-reported physician diagnosis of any cancer (excluding nonmelanoma skin cancer) during follow-up. Main Outcomes and Measures: A composite memory score standardized to a mean (SD) of 0 (1) at baseline was based on immediate and delayed word-list recall and proxy assessments. The rate of memory change among people diagnosed with cancer during follow-up before and after diagnosis was compared with rate of memory change in individuals who remained cancer free during follow-up using linear mixed-effect models with random intercepts and slopes. Results: A total of 14 583 participants were included in the sample (mean [SD] age, 66.4 [10.4] years; 8453 [58.0%] female). The mean (SD) follow-up was 11.5 (5.1) years; 2250 had a cancer diagnosis during follow-up, and 12 333 had no cancer diagnosis during follow-up. The rate of memory decline in the decade before a cancer diagnosis was 10.5% (95% CI, 6.2%-14.9%), which was slower than memory decline in similarly aged cancer-free individuals. For individuals diagnosed at 75 years of age, mean memory function immediately before diagnosis was 0.096 SD units (95% CI, 0.060-0.133 SD units) higher compared with that among similarly aged cancer-free individuals. A new cancer diagnosis was associated with a short-term decline in memory of -0.058 (95% CI, -0.084 to -0.032) SD units compared with memory before diagnosis. After diagnosis, the rate of memory decline was 3.9% (95% CI, 0.9%-6.9%) slower in individuals with cancer than in those without a cancer diagnosis. Conclusions and Relevance: In this study, older individuals who developed cancer had better memory and slower memory decline than did similarly aged individuals who remained cancer free. These findings support the possibility of a common pathologic process working in opposite directions in cancer and Alzheimer disease.

Caregivers' Self-Reported Absence of Social Support Networks is Related to Treatment Abandonment in Children With Cancer.

BACKGROUND: Treatment abandonment (TxA) is a primary cause of therapy failure in children with cancer in low-/middle-income countries. We explored the absence of social support network (SSN), among other predictive factors, and TxA in children with cancer in Cali, Colombia. PROCEDURE: In this prospective cohort study, we included children diagnosed with cancer at a public university hospital. A social worker and a psychologist administered semistructured questionnaires to patients' caregivers. We extracted information from the questionnaires about social, economic, and psychological conditions of the patients' families. Outcomes were death, relapse, and TxA. Failure either to start or to continue the planned course of curative treatment for 4 weeks or more was defined as TxA. We identified events with Cali's childhood cancer outcomes surveillance system (VIGICANCER). We adjusted the hazard ratios (HRs) for potential confounders using multivariate Cox regression analyses. RESULTS: Among 188 patients diagnosed from January 2011 to June 2013, 99 interviews were conducted. Median age was 5 years old (range: 0.3, 14.9), 53% were male, 17% were of Colombian-Indian ethnicity, and 68% lived in rural areas. The 2-year cumulative incidence of TxA was 21% (95% confidence interval [CI]: 13, 35) and the annual proportion was 14%. The adjusted HR for the absence of SSN was 4.9 (95% CI: 1.6, 15.3). CONCLUSIONS: We found a strong association between the absence of SSN and TxA that was independent of other covariates, including surrogate measures of wealth. Our findings highlight the imperative understanding of social ties and support surrounding children's families for planning strategies to prevent TxA.