Identifying Cancer-Related Cognitive Impairment Using the FACT-Cog Perceived Cognitive Impairment.

Cancer-related cognitive impairment (CRCI) is a concerning problem for many cancer survivors. Evaluating patients for CRCI has been a challenge, in part because of a lack of standardized practices. Self-report instruments are often used to assess CRCI, but there are no validated cutpoints. We present the results of receiver operating characteristic curve analysis identifying cutpoints of the Functional Assessment of Cancer Therapy-Cognition perceived cognitive impairment (PCI) in female breast cancer survivors for identifying CRCI cases. We defined presence of CRCI based on elevated complaints on the Patient's Assessment of Own Functioning Inventory compared with healthy control scores. Our results indicate that scores less than 54 in PCI scores using 18 items and scores less than 60 in PCI scores using 20 items exhibited good ability to discriminate CRCI cases from noncases (area under the receiver operating characteristic curve was 0.84 [95% CI = 0.73 to 0.94]). These preliminary results represent an important contribution toward standardizing practices across CRCI studies

25-Hydroxy vitamin-D, obesity, and associated variables as predictors of breast cancer risk and tamoxifen benefit in NSABP-P1.

Observational studies suggest that host factors are associated with breast cancer risk. The influence of obesity, vitamin-D status, insulin resistance, inflammation, and elevated adipocytokines in women at high risk of breast cancer is unknown. The NSABP-P1 trial population was used for a nested case-control study. Cases were drawn from those who developed invasive breast cancer and controls selected from unaffected participants (≤4 per case) matched for age, race, 5 year Gail score, and geographic location of clinical center as a surrogate for latitude. Fasting serum banked at trial enrolment was assayed for 25-hydroxy vitamin-D (25OHD), insulin, leptin (adipocytokine), and C-reactive protein (CRP, marker of inflammation). Logistic regression was used to test for associations between study variables and the risk of invasive breast cancer. Two hundred and thirty-one cases were matched with 856 controls. Mean age was 54, and 49% were premenopausal. There were negative correlations for 25OHD with body mass index (BMI), insulin, CRP, and leptin. BMI ≥ 25 kg/m(2) was associated with higher breast cancer risk (odds ratio [OR] 1.45, p = 0.02) and tamoxifen treatment was associated with lower risk (OR = 0.44, p < 0.001). Suboptimal 25OHD (<72 nmol/l) did not influence breast cancer risk (OR = 1.06, p = 0.76). When evaluated as continuous variables, 25OHD, insulin, CRP, and leptin levels were not associated with breast cancer risk (all p > 0.34). In this high risk population, higher BMI was associated with a greater breast cancer risk. Serum levels of 25OHD, insulin, CRP, and leptin were not independent predictors of either breast cancer risk or tamoxifen benefit

Childhood maltreatment, psychological resources, and depressive symptoms in women with breast cancer.

Childhood maltreatment is associated with elevated risk for depression across the human lifespan. Identifying the pathways through which childhood maltreatment relates to depressive symptoms may elucidate intervention targets that have the potential to reduce the lifelong negative health sequelae of maltreatment exposure. In this cross-sectional study, 271 women with early-stage breast cancer were assessed after their diagnosis but before the start of adjuvant treatment (chemotherapy, radiation, endocrine therapy). Participants completed measures of childhood maltreatment exposure, psychological resources (optimism, mastery, self-esteem, mindfulness), and depressive symptoms. Using multiple mediation analyses, we examined which psychological resources uniquely mediated the relationship between childhood maltreatment and depressive symptoms. Exposure to maltreatment during childhood was robustly associated with lower psychological resources and elevated depressive symptoms. Further, lower optimism and mindfulness mediated the association between childhood maltreatment and elevated depressive symptoms. These results support existing theory that childhood maltreatment is associated with lower psychological resources, which partially explains elevated depressive symptoms in a sample of women facing breast cancer diagnosis and treatment. These findings warrant replication in populations facing other major life events and highlight the need for additional studies examining childhood maltreatment as a moderator of treatment outcomes

Correlates of quality of life in overweight or obese breast cancer survivors at enrollment into a weight loss trial

OBJECTIVE: To examine the correlates of the physical and psychosocial domains of quality of life (QOL) in a cohort of breast cancer survivors participating in a weight loss intervention trial. Available data included information on weight and physical activity, as well as demographic and medical characteristics. METHODS: Correlates of QOL and psychosocial functioning were examined in 692 overweight/obese breast cancer survivors at entry into a weight loss trial. QOL was explored with three measures: Short-form 36 (SF-36); Impact of Cancer Scale (IOCv2); and the Breast Cancer Prevention Trial (BCPT) Symptom Scales. Bivariate and multivariate analyses were used to identify correlates and associations adjusted for other characteristics. RESULTS: In multivariate analysis, younger age was associated with higher negative impact scores (p<0.01). Hispanic, African-American and Asian women had higher IOC positive impact scores compared to white non-Hispanic women (p<0.01). Higher education was associated with lower scores on mental QOL and the IOC positive impact scale (p<0.01). BMI was not independently associated with QOL measures. Physical activity was directly associated with physical and mental QOL and IOC positive impact, and inversely related to IOC negative impact and BCPT symptom scales. CONCLUSIONS: QOL measures in breast cancer survivors are differentially associated with demographic and other characteristics. When adjusted for these characteristics, degree of adiposity among overweight/obese women does not appear to be independently associated with QOL. Among overweight/obese breast cancer survivors, higher level of physical activity is associated with higher QOL across various scales and dimensions

DNA methylation age is elevated in breast tissue of healthy women

BACKGROUND: Limited evidence suggests that female breast tissue ages faster than other parts of the body according to an epigenetic biomarker of aging known as the "epigenetic clock." However, it is unknown whether breast tissue samples from healthy women show a similar accelerated aging effect relative to other tissues, and what could drive this acceleration. The goal of this study is to validate our initial finding of advanced DNA methylation (DNAm) age in breast tissue, by directly comparing it to that of peripheral blood tissue from the same individuals, and to do a preliminary assessment of hormonal factors that could explain the difference. METHODS: We utilized n = 80 breast and 80 matching blood tissue samples collected from 40 healthy female participants of the Susan G. Komen Tissue Bank at the Indiana University Simon Cancer Center who donated these samples at two time points spaced at least a year apart. DNA methylation levels (Illumina 450K platform) were used to estimate the DNAm age. RESULTS: DNAm age was highly correlated with chronological age in both peripheral blood (r = 0.94, p < 0.0001) and breast tissues (r = 0.86, p < 0.0001). A measure of epigenetic age acceleration (age-adjusted DNAm Age) was substantially increased in breast relative to peripheral blood tissue (p = 1.6 × 10-11). The difference between DNAm age of breast and blood decreased with advancing chronologic age (r = -0.53, p = 4.4 × 10-4). CONCLUSIONS: Our data clearly demonstrate that female breast tissue has a higher epigenetic age than blood collected from the same subject. We also observe that the degree of elevation in breast diminishes with advancing age. Future larger studies will be needed to examine associations between epigenetic age acceleration and cumulative hormone exposure

Biomarkers of aging associated with past treatments in breast cancer survivors.

Radiation and chemotherapy are effective treatments for cancer, but are also toxic to healthy cells. Little is known about whether prior exposure to these treatments is related to markers of cellular aging years later in breast cancer survivors. We examined whether past exposure to chemotherapy and/or radiation treatment was associated with DNA damage, telomerase activity, and telomere length 3-6 years after completion of primary treatments in breast cancer survivors (stage 0-IIIA breast cancer at diagnosis). We also examined the relationship of these cellular aging markers with plasma levels of Interleukin (IL)-6, soluble TNF-receptor-II (sTNF-RII), and C-reactive protein (CRP). Ninety-four women (36.4-69.5 years; 80% white) were evaluated. Analyses adjusting for age, race, BMI, and years from last treatment found that women who had prior exposure to chemotherapy and/or radiation compared to women who had previously received surgery alone were more likely to have higher levels of DNA damage (P = .02) and lower telomerase activity (P = .02), but did not have differences in telomere length. More DNA damage and lower telomerase were each associated with higher levels of sTNF-RII (P's &lt; .05). We found that exposure to chemotherapy and/or radiation 3-6 years prior was associated with markers of cellular aging, including higher DNA damage and lower telomerase activity, in post-treatment breast cancer survivors. Furthermore, these measures were associated with elevated inflammatory activation, as indexed by sTNF-RII. Given that these differences were observed many years after the treatment, the findings suggest a long lasting effect of chemotherapy and/or radiation exposure

Facets of spirituality as predictors of adjustment to cancer: Relative contributions of having faith and finding meaning

Spirituality is a multidimensional construct, and little is known about how its distinct dimensions jointly affect well-being. In longitudinal studies (Study 1, n = 418 breast cancer patients; Study 2, n = 165 cancer survivors), the authors examined 2 components of spiritual well-being (i.e., meaning/peace and faith) and their interaction, as well as change scores on those variables, as predictors of psychological adjustment. In Study 1, higher baseline meaning/peace, as well as an increase in meaning/peace over 6 months, predicted a decline in depressive symptoms and an increase in vitality across 12 months in breast cancer patients. Baseline faith predicted an increase in perceived cancer-related growth. Study 2 revealed that an increase in meaning/peace was related to improved mental health and lower cancer-related distress. An increase in faith was related to increased cancer-related growth. Both studies revealed significant interactions between meaning/peace and faith in predicting adjustment. Findings suggest that the ability to find meaning and peace in life is the more influential contributor to favorable adjustment during cancer survivorship, although faith appears to be uniquely related to perceived cancer-related growth

Cancer survivorship research: the challenge of recruiting adult long term cancer survivors from a cooperative clinical trials group

With the growing number of adult cancer survivors, there is increasing need for information that links potential late and long term effects with specific treatment regimens. Few adult cancer patients are treated on clinical trials; however, patients previously enrolled in these trials are an important source of information about treatment-related late effects. Focusing on colorectal cancer survivors, we used the database from five phase III randomized clinical trials from the National Surgical Adjuvant Breast &amp; Bowel Project (NSABP) to recruit and enroll long term survivors in a study of late health outcomes and quality of life. We describe the challenges to recruitment of patients more than 5 –20 years after treatment. Sixty-five NSABP treatment sites were invited to enroll patients in the study. Sixty participated with the potential to recruit 2,408 patients. We received registration forms on only 976 patients (41%) of whom 744 (76%) expressed interest in participating and 708 completed interviews (95% of those expressing interest; 29% of total potential sample). There were multiple barriers to recruitment (difficulty locating patients, lack of institutional commitment, lack of patient interest). Patients treated on clinical trials are an important potential source for examining the late effects of cancer treatments. Retrospective recruitment has substantial limitations. In the future, mechanisms should be established for prospective long-term follow-up to identify and understand the frequency and type of late effects associated with cancer treatments. As cancer patients are living longer, it will be important to learn from participants in clinical trials whether or not specific treatment regimens are associated with any serious late effects