Risk factors for self-reported arm lymphedema among female breast cancer survivors: a prospective cohort study.

INTRODUCTION: Lymphedema is a potentially debilitating condition that occurs among breast cancer survivors. This study examines the incidence of self-reported lymphedema, timing of lymphedema onset, and associations between sociodemographic, clinical and lifestyle factors and lymphedema risk across racial-ethnic groups using data from a multicenter, multiethnic prospective cohort study of breast cancer survivors, the Health, Eating, Activity and Lifestyle Study. METHODS: A total of 666 women diagnosed with breast cancer staged as in situ, localized or regional disease at ages 35 to 64 years were recruited through the Surveillance, Epidemiology, and End Results registries in New Mexico (non-Hispanic white and Hispanic white), Los Angeles County (black), and Western Washington (non-Hispanic white) and followed for a median of 10.2 years. We evaluated sociodemographic factors, breast cancer- and treatment-related factors, comorbidities, body mass index (BMI), hormonal factors, and lifestyle factors in relation to self-reported lymphedema by fitting Cox proportional hazards models, estimating hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: Over the follow-up period, 190 women (29%) reported lymphedema. The median time from breast cancer diagnosis to onset of lymphedema was 10.5 months (range: 0.5 to 134.9 months). Factors independently associated with lymphedema were total/modified radical mastectomy (versus partial/less than total mastectomy; HR = 1.37, 95% CI: 1.01 to 1.85), chemotherapy (versus no chemotherapy; HR = 1.48, 95% CI: 1.09 to 2.02), no lymph nodes removed (versus ≥10 lymph nodes removed; HR = 0.17, 95% CI: 0.08 to 0.33), pre-diagnostic BMI ≥30 kg/m2 (versus BMI <25 kg/m2; HR = 1.59, 95% CI: 1.09 to 2.31), and hypertension (versus no hypertension; HR = 1.49, 95% CI: 1.06 to 2.10). After adjusting for demographics and breast cancer- and treatment-related factors, no significant difference in lymphedema risk was observed across racial/ethnic groups. Analyses stratified by race/ethnicity showed that hypertension and chemotherapy were lymphedema risk factors only for black women. CONCLUSIONS: Breast cancer patients who have undergone extensive surgery or extensive lymph node dissection, or who have a higher BMI should be closely monitored for detection and treatment of lymphedema. Further studies are needed to understand the roles of chemotherapy and hypertension in the development of lymphedema.

Physical activity and cancer-specific mortality in the NIH-AARP Diet and Health Study cohort.

Higher physical activity levels have been associated with a lower risk of developing various cancers and all-cancer mortality, but the impact of pre-diagnosis physical activity on cancer-specific death has not been fully characterized. In the prospective National Institutes of Health-AARP Diet and Health Study with 293,511 men and women, we studied prediagnosis moderate to vigorous intensity leisure time physical activity (MVPA) in the past 10 years and cancer-specific mortality. Over a median 12.1 years, we observed 15,001 cancer deaths. Using Cox proportional hazards regression, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for MVPA with cancer mortality overall and by 20 specific cancer sites, adjusting for relevant risk factors. Compared to participants reporting never/rare MVPA, those reporting >7 hr/week MVPA had a lower risk of total cancer mortality (HR = 0.89, 95% CI 0.84-0.94; p-trend <0.001). When analyzed by cancer site-specific deaths, comparing those reporting >7 hr/week of MVPA to those reporting never/rare MVPA, we observed a lower risk of death from colon (HR = 0.70; 95% CI 0.57-0.85; p-trend <0.001), liver (0.71; 0.52-0.98; p-trend = 0.012) and lung cancer (0.84; 0.77-0.92; p-trend <0.001) and a significant p-trend for non-Hodgkins lymphoma (0.80; 0.62-1.04; p-trend = 0.017). An unexpected increased mortality p-trend with increasing MVPA was observed for death from kidney cancer (1.42; 0.98-2.03; p-trend = 0.016). Our findings suggest that higher prediagnosis leisure time physical activity is associated with lower risk of overall cancer mortality and mortality from multiple cancer sites. Future studies should confirm observed associations and further explore timing of physical activity and underlying biological mechanisms.

Association between class III obesity (BMI of 40-59 kg/m2) and mortality: a pooled analysis of 20 prospective studies.

BACKGROUND: The prevalence of class III obesity (body mass index [BMI]≥40 kg/m2) has increased dramatically in several countries and currently affects 6% of adults in the US, with uncertain impact on the risks of illness and death. Using data from a large pooled study, we evaluated the risk of death, overall and due to a wide range of causes, and years of life expectancy lost associated with class III obesity. METHODS AND FINDINGS: In a pooled analysis of 20 prospective studies from the United States, Sweden, and Australia, we estimated sex- and age-adjusted total and cause-specific mortality rates (deaths per 100,000 persons per year) and multivariable-adjusted hazard ratios for adults, aged 19-83 y at baseline, classified as obese class III (BMI 40.0-59.9 kg/m2) compared with those classified as normal weight (BMI 18.5-24.9 kg/m2). Participants reporting ever smoking cigarettes or a history of chronic disease (heart disease, cancer, stroke, or emphysema) on baseline questionnaires were excluded. Among 9,564 class III obesity participants, mortality rates were 856.0 in men and 663.0 in women during the study period (1976-2009). Among 304,011 normal-weight participants, rates were 346.7 and 280.5 in men and women, respectively. Deaths from heart disease contributed largely to the excess rates in the class III obesity group (rate differences = 238.9 and 132.8 in men and women, respectively), followed by deaths from cancer (rate differences = 36.7 and 62.3 in men and women, respectively) and diabetes (rate differences = 51.2 and 29.2 in men and women, respectively). Within the class III obesity range, multivariable-adjusted hazard ratios for total deaths and deaths due to heart disease, cancer, diabetes, nephritis/nephrotic syndrome/nephrosis, chronic lower respiratory disease, and influenza/pneumonia increased with increasing BMI. Compared with normal-weight BMI, a BMI of 40-44.9, 45-49.9, 50-54.9, and 55-59.9 kg/m2 was associated with an estimated 6.5 (95% CI: 5.7-7.3), 8.9 (95% CI: 7.4-10.4), 9.8 (95% CI: 7.4-12.2), and 13.7 (95% CI: 10.5-16.9) y of life lost. A limitation was that BMI was mainly ascertained by self-report. CONCLUSIONS: Class III obesity is associated with substantially elevated rates of total mortality, with most of the excess deaths due to heart disease, cancer, and diabetes, and major reductions in life expectancy compared with normal weight. Please see later in the article for the Editors' Summary.

Body mass and weight change in adults in relation to mortality risk.

Using data from the National Institutes of Health-AARP Diet and Health Study, we evaluated the influence of adulthood weight history on mortality risk. The National Institutes of Health-AARP Diet and Health Study is an observational cohort study of US men and women who were aged 50-71 years at entry in 1995-1996. This analysis focused on 109,947 subjects who had never smoked and were younger than age 70 years. We estimated hazard ratios of total and cause-specific mortality for recalled body mass index (BMI; weight (kg)/height (m)(2)) at ages 18, 35, and 50 years; weight change across 3 adult age intervals; and the effect of first attaining an elevated BMI at 4 successive ages. During 12.5 years' follow-up through 2009, 12,017 deaths occurred. BMI at all ages was positively related to mortality. Weight gain was positively related to mortality, with stronger associations for gain between ages 18 and 35 years and ages 35 and 50 years than between ages 50 and 69 years. Mortality risks were higher in persons who attained or exceeded a BMI of 25.0 at a younger age than in persons who reached that threshold later in adulthood, and risks were lowest in persons who maintained a BMI below 25.0. Heavier initial BMI and weight gain in early to middle adulthood strongly predicted mortality risk in persons aged 50-69 years.

Comparing indices of diet quality with chronic disease mortality risk in postmenopausal women in the Women's Health Initiative Observational Study: evidence to inform national dietary guidance.

Poor diet quality is thought to be a leading risk factor for years of life lost. We examined how scores on 4 commonly used diet quality indices-the Healthy Eating Index 2010 (HEI), the Alternative Healthy Eating Index 2010 (AHEI), the Alternate Mediterranean Diet (aMED), and the Dietary Approaches to Stop Hypertension (DASH)-are related to the risks of death from all causes, cardiovascular disease (CVD), and cancer among postmenopausal women. Our prospective cohort study included 63,805 participants in the Women's Health Initiative Observational Study (from 1993-2010) who completed a food frequency questionnaire at enrollment. Cox proportional hazards models were fit using person-years as the underlying time metric. We estimated multivariate hazard ratios and 95% confidence intervals for death associated with increasing quintiles of diet quality index scores. During 12.9 years of follow-up, 5,692 deaths occurred, including 1,483 from CVD and 2,384 from cancer. Across indices and after adjustment for multiple covariates, having better diet quality (as assessed by HEI, AHEI, aMED, and DASH scores) was associated with statistically significant 18%-26% lower all-cause and CVD mortality risk. Higher HEI, aMED, and DASH (but not AHEI) scores were associated with a statistically significant 20%-23% lower risk of cancer death. These results suggest that postmenopausal women consuming a diet in line with a priori diet quality indices have a lower risk of death from chronic disease.

Central adiposity after breast cancer diagnosis is related to mortality in the Health, Eating, Activity, and Lifestyle study.

We examined whether waist circumference (WC) and waist-to-hip ratio (WHR) after breast cancer diagnosis are associated with all-cause or breast cancer-specific mortality and explored potential biological pathways mediating these relationships. Our analysis included 621 women diagnosed with local or regional breast cancer who participated in the Health, Eating, Activity, and Lifestyle study. At 30 (±4) months postdiagnosis, trained staff measured participants' waist and hip circumferences and obtained fasting serum samples for biomarker assays for assays of insulin, glucose, C-peptide, insulin growth factor-1 and binding protein-3, C-reactive protein (CRP), and adiponectin. We estimated multivariate hazard ratios (HR) and 95 % confidence intervals (CI) for death over ~9.5 years of follow-up. After adjustment for measured body mass index, treatment, comorbidities, race/ethnicity, diet quality, and postdiagnosis physical activity, WC was positively associated with all-cause mortality (HRq4:q1: 2.99, 95 % CI 1.14, 7.86) but its positive association with breast cancer-specific mortality was not statistically significant (HRq4:q1: 2.69, 95 % CI 0.69, 12.01). WHR was positively associated with all-cause mortality (HRq4:q1: 2.10, 95 % CI 1.08, 4.05) and breast cancer-specific mortality (HRq4:q1: 4.02, 95 % CI 1.31, 12.31). After adjustment for homeostatic model assessment (HOMA) score and C-reactive protein, risk estimates were attenuated and not statistically significant. In this diverse breast cancer survivor cohort, postdiagnosis WC and WHR were associated with all-cause mortality. Insulin resistance and inflammation may mediate the effects of central adiposity on mortality among breast cancer patients.

Neighborhood-level socioeconomic deprivation predicts weight gain in a multi-ethnic population: longitudinal data from the Dallas Heart Study.

OBJECTIVE: The aim of this study is to examine a relationship between neighborhood-level socioeconomic deprivation and weight change in a multi-ethnic cohort from Dallas County, Texas and whether behavioral/psychosocial factors attenuate the relationship. METHODS: Non-movers (those in the same neighborhood throughout the study period) aged 18-65 (N=939) in Dallas Heart Study (DHS) underwent weight measurements between 2000 and 2009 (median 7-year follow-up). Geocoded home addresses defined block groups; a neighborhood deprivation index (NDI) was created (higher NDI=greater deprivation). Multi-level modeling determined weight change relative to NDI. Model fit improvement was examined with adding physical activity and neighborhood environment perceptions (higher score=more unfavorable perceptions) as covariates. A significant interaction between residence length and NDI was found (p-interaction=0.04); results were stratified by median residence length (11 years). RESULTS: Adjusting for age, sex, race/ethnicity, smoking, and education/income, those who lived in neighborhood >11 years gained 1.0 kg per one-unit increment of NDI (p=0.03), or 6 kg for those in highest NDI tertile compared with those in the lowest tertile. Physical activity improved model fit; NDI remained associated with weight gain after adjustment for physical activity and neighborhood environment perceptions. There was no significant relationship between NDI and weight change for those in their neighborhood ≤11 years. CONCLUSIONS: Living in more socioeconomically deprived neighborhoods over a longer time period was associated with weight gain in DHS.

Urban sprawl, obesity, and cancer mortality in the United States: cross-sectional analysis and methodological challenges.

BACKGROUND: Urban sprawl has the potential to influence cancer mortality via direct and indirect effects on obesity, access to health services, physical activity, transportation choices and other correlates of sprawl and urbanization. METHODS: This paper presents a cross-sectional analysis of associations between urban sprawl and cancer mortality in urban and suburban counties of the United States. This ecological analysis was designed to examine whether urban sprawl is associated with total and obesity-related cancer mortality and to what extent these associations differed in different regions of the US. A major focus of our analyses was to adequately account for spatial heterogeneity in mortality. Therefore, we fit a series of regression models, stratified by gender, successively testing for the presence of spatial heterogeneity. Our resulting models included county level variables related to race, smoking, obesity, access to health services, insurance status, socioeconomic position, and broad geographic region as well as a measure of urban sprawl and several interactions. Our most complex models also included random effects to account for any county-level spatial autocorrelation that remained unexplained by these variables. RESULTS: Total cancer mortality rates were higher in less sprawling areas and contrary to our initial hypothesis; this was also true of obesity related cancers in six of seven U.S. regions (census divisions) where there were statistically significant associations between the sprawl index and mortality. We also found significant interactions (p < 0.05) between region and urban sprawl for total and obesity related cancer mortality in both sexes. Thus, the association between urban sprawl and cancer mortality differs in different regions of the US. CONCLUSIONS: Despite higher levels of obesity in more sprawling counties in the US, mortality from obesity related cancer was not greater in such counties. Identification of disparities in cancer mortality within and between geographic regions is an ongoing public health challenge and an opportunity for further analytical work identifying potential causes of these disparities. Future analyses of urban sprawl and health outcomes should consider exploring regional and international variation in associations between sprawl and health.

Associations of insulin-like growth factor and insulin-like growth factor binding protein-3 with mortality in women with breast cancer.

Elevated circulating insulin-like growth factor-1 (IGF-1), a breast epithelial cell mitogen, is associated with breast cancer development. However, its association with breast cancer survival is not established. Circulating concentrations of IGF-1 are controlled via binding proteins, including IGF Binding Protein-3 (IGFBP-3), that may modulate the association of IGF-1 with breast-cancer outcomes. We measured IGF-1 and IGFBP-3 concentrations in serum from 600 women enrolled in the health, eating, activity, and lifestyle (HEAL) study, a multiethnic, prospective cohort study of women diagnosed with stage I-IIIA breast cancer. We evaluated the association between IGF-1 and IGFBP-3, and as a ratio, modeled using quintile cut-points, with risk of breast cancer-specific (n = 42 deaths) and all-cause mortality (n = 87 deaths) using Cox proportional hazards models. In models adjusted for body mass index, ethnicity, tamoxifen use at time of blood draw, treatment received at diagnosis and IGFBP-3, women in the highest quintile of IGF-1 level had an increased risk of all-cause mortality (Hazard Ratio (HR) = 3.10, 95% CI 1.21-7.93, p = 0.02), although no dose-response association was evident. The IGF-1/IGFBP-3 ratio, an indicator of free IGF-I levels, was significantly associated with increasing risk of all-cause mortality (HR = 2.83, 95% CI 1.25-6.36 p(trend) = 0.01, upper vs. lower quintile) in a fully adjusted model. In conclusion, high serum levels of IGF-1 and the IGF-1/IGFBP-3 ratio were associated with increased risk of all-cause mortality in women with breast cancer. These results need to be confirmed in larger breast cancer survivor cohorts.

Pain in long-term breast cancer survivors: the role of body mass index, physical activity, and sedentary behavior.

Although pain is common among post-treatment breast cancer survivors, studies that are longitudinal, identify a case definition of clinically meaningful pain, or examine factors contributing to pain in survivors are limited. This study describes longitudinal patterns of pain in long-term breast cancer survivors, evaluating associations of body mass index (BMI), physical activity, sedentary behavior with mean pain severity and above-average pain. Women newly diagnosed with stages 0-IIIA breast cancer (N = 1183) were assessed, on average, 6 months (demographic/clinical characteristics), 30 months (demographics), 40 months (demographics, pain), 5 years (BMI, physical activity, and sedentary behavior), and 10 years (demographics, pain, BMI, physical activity, and sedentary behavior) post-diagnosis. This analysis includes survivors who completed pain assessments 40 months post-diagnosis (N = 801), 10 years post-diagnosis (N = 563), or both (N = 522). Above-average pain was defined by SF-36 bodily pain scores ≥1/2 standard deviation worse than age-specific population norms. We used multiple regression models to test unique associations of BMI, physical activity, and sedentary behavior with pain adjusting for demographic and clinical factors. The proportion of survivors reporting above-average pain was higher at 10 years than at 40 months (32.3 vs. 27.8 %, p < 0.05). Approximately one-quarter of survivors reported improved pain, while 9.0 % maintained above-average pain and 33.1 % reported worsened pain. Cross-sectionally at 10 years, overweight and obese survivors reported higher pain than normal-weight survivors and women meeting physical activity guidelines were less likely to report above-average pain than survivors not meeting these guidelines (p < 0.05). Longitudinally, weight gain (>5 %) was positively associated, while meeting physical activity guidelines was inversely associated, with above-average pain (OR, 95 % CI = 1.76, 1.03-3.01 and 0.40, 0.20-0.84, respectively) (p < 0.05). Weight gain and lack of physical activity place breast cancer survivors at risk for pain long after treatment ends. Weight control and exercise interventions should be tested for effects on long-term pain in these women.

Weight, inflammation, cancer-related symptoms and health related quality of life among breast cancer survivors.

Maintaining weight is important for better prognosis of breast cancer survivors. The associations between weight and cancer-related symptoms are not known. We examined associations among weight, weight change, inflammation, cancer-related symptoms, and health-related quality of life (HRQOL) in a cohort of stage 0-IIIA breast cancer survivors. Participants were recruited on average 6 months (2­12 months) after diagnosis. Height, weight, and C-reactive protein (CRP) were assessed at approximately 30 months post-diagnosis; cancer-related symptoms (chest wall and arm symptoms, vasomotor symptoms, urinary incontinence, vaginal symptoms, cognition/mood problems, sleep, sexual interest/function), and HRQOL (SF-36) were assessed at approximately 40 months post-diagnosis. Weight was measured at baseline in a subset. Data on 661 participants were evaluable for body mass index (BMI); 483 were evaluable for weight change. We assessed associations between BMI (<25.0, 25.0­29.9, ≥30.0 kg/m2), post-diagnosis weight change (lost ≥5 %, weight change <5 %, gained ≥5 %), and CRP (tertile) with cancer-related symptoms and HRQOL using analysis of covariance. Higher symptoms scores indicate more frequent or severe symptoms. Higher HRQOL scores indicate better HRQOL. Compared with those with BMI <25 kg/m2, women with BMI ≥30 kg/m2 had the following scores: increased for arm symptoms (+25.0 %), urinary incontinence (+40.0 %), tendency to nap (+18.9 %), and poorer physical functioning (−15.6 %, all p < 0.05). Obese women had lower scores in trouble falling asleep (−9.9 %; p < 0.05). Compared with weight change <5 %, participants with ≥5 % weight gain had lower scores in physical functioning (−7.2 %), role-physical (−15.5 %) and vitality (−11.2 %), and those with weight loss ≥5 % had lower chest wall (−33.0 %) and arm symptom scores (−35.5 %, all p < 0.05). Increasing CRP tertile was associated with worse scores for chest wall symptoms, urinary incontinence, physical functioning, role-physical, vitality and physical component summary scores (all P trend < 0.05). Future studies should examine whether interventions to maintain a healthy weight and reduce inflammation could alleviate cancer-related symptoms and improve HRQOL.

Associations of serum 25-hydroxyvitamin D with overall and breast cancer-specific mortality in a multiethnic cohort of breast cancer survivors.

PURPOSE: Despite limited evidence on the association of vitamin D with outcomes in breast cancer survivors, some clinicians advise breast cancer patients to use vitamin D supplements. More evidence is needed to inform these recommendations. METHODS: In the Health, Eating, Activity, and Lifestyle study, we examined associations of post-treatment serum concentrations of 25-hydroxyvitamin D (25(OH)D) on overall and breast cancer-specific mortality in 585 breast cancer survivors from western Washington State, New Mexico, and Los Angeles County. 25(OH)D was measured in stored blood collected 2 years post-enrollment. Outcomes were ascertained from the Surveillance, Epidemiology, and End Results registries and medical records. Cox proportional hazards models were fit to assess associations of serum 25(OH)D with overall and breast cancer-specific mortality. RESULTS: After a median follow-up of 9.2 years; 110 women died, including 48 from breast cancer. Standard cut points classified 211 (31.6 %) women as serum 25(OH)D deficient (<20 ng/mL), 189 (32.2 %) as insufficient (20-30 ng/mL), and 185 (36.2 %) as sufficient (>30 ng/mL). Compared to women with deficient 25(OH)D, those in the sufficient ranges had a decreased risk of overall mortality (age-adjusted HR = 0.58; 95 % CI 0.36-0.96); however, multivariate adjustments attenuated the association (HR = 0.90; 95 % CI 0.50-1.61). No association was found between serum 25(OH)D and breast cancer-specific mortality (sufficient: HR = 1.21; 95 % CI 0.52-2.80) in multivariate models. CONCLUSION: In this breast cancer cohort, higher serum 25(OH)D may be associated with improved survival, but results were not statistically significant and must be interpreted with caution. The potential prognostic effect of vitamin D from diet, supplements, or both should be evaluated in future larger studies with additional endpoints from breast cancer patients.

Body mass index, tumor characteristics, and prognosis following diagnosis of early-stage breast cancer in a mammographically screened population.

PURPOSE: Many studies suggest increased body mass index (BMI) is associated with worse breast cancer outcomes, but few account for variability in screening, access to treatment, and tumor differences. We examined the association between BMI and risk of breast cancer recurrence, breast cancer-specific mortality, and all-cause mortality, and evaluated whether tumor characteristics differ by BMI among a mammographically screened population with access to treatment. METHODS: Using a retrospective cohort study design, we followed 485 women aged ≥40 years diagnosed with stage I/II breast cancer within 24 months of a screening mammogram occurring between 1988 and 1993 for 10-year outcomes. BMI before diagnosis was categorized as normal (<25 kg/m(2)), overweight (25-29.9 kg/m(2)), and obese (≥30 kg/m(2)). Tumor marker expression was assessed via immunohistochemistry using tissue collected before adjuvant treatment. Medical records were abstracted to identify treatment, recurrence, and mortality. We used Cox proportional hazards to separately model the hazard ratios (HR) of our three outcomes by BMI while adjusting for age, stage, and tamoxifen use. RESULTS: Relative to normal-weight women, obese women experienced increased risk of recurrence (HR 2.43; 95 % CI 1.34-4.41) and breast cancer death (HR 2.41; 95 % CI 1.00-5.81) within 10 years of diagnosis. There was no association between BMI and all-cause mortality. Obese women had significantly faster growing tumors, as measured by Ki-67. CONCLUSIONS: Our findings add to the growing evidence that obesity may contribute to poorer breast cancer outcomes, and also suggest that increased tumor proliferation among obese women is a pathway that explains part of their excess risk of adverse outcomes.

Disentangling the body weight-bone mineral density association among breast cancer survivors: an examination of the independent roles of lean mass and fat mass.

BACKGROUND: Bone mineral density (BMD) and lean mass (LM) may both decrease in breast cancer survivors, thereby increasing risk of falls and fractures. Research is needed to determine whether lean mass (LM) and fat mass (FM) independently relate to BMD in this patient group. METHODS: The Health, Eating, Activity, and Lifestyle Study participants included 599 women, ages 29-87 years, diagnosed from 1995-1999 with stage 0-IIIA breast cancer, who underwent dual-energy X-ray absorptiometry scans approximately 6-months postdiagnosis. We calculated adjusted geometric means of total body BMD within quartiles (Q) of LM and FM. We also stratified LM-BMD associations by a fat mass index threshold that tracks with obesity (lower body fat: ≤ 12.9 kg/m2; higher body fat: >12.9 kg/m2) and stratified FM-BMD associations by appendicular lean mass index level corresponding with sarcopenia (non-sarcopenic: ≥ 5.45 kg/m2 and sarcopenic: < 5.45 kg/m2). RESULTS: Higher LM (Q4 vs. Q1) was associated with higher total body BMD overall (1.12 g/cm2 vs. 1.07 g/cm2, p-trend < 0.0001), and among survivors with lower body fat (1.13 g/cm2 vs. 1.07 g/cm2, p-trend < 0.0001) and higher body fat (1.15 g/cm2 vs. 1.08 g/cm2, p-trend = 0.004). Higher FM (Q4 vs. Q1) was associated with higher total body BMD overall (1.12 g/cm2 vs. 1.07 g/cm2, p-trend < 0.0001) and among non-sarcopenic survivors (1.15 g/cm2 vs. 1.08 g/cm2, p < 0.0001), but the association was not significant among sarcopenic survivors (1.09 g/cm2 vs. 1.04 g/cm2, p-trend = 0.18). CONCLUSION: Among breast cancer survivors, higher LM and FM were independently related to higher total body BMD. Future exercise interventions to prevent bone loss among survivors should consider the potential relevance of increasing and preserving LM.

Deriving clinically meaningful cut-scores for fatigue in a cohort of breast cancer survivors: a Health, Eating, Activity, and Lifestyle (HEAL) Study.

PURPOSE: To empirically determine clinically meaningful cut-scores on the 0-10 response scale of the revised Piper Fatigue Scale (PFS-R) and its shorter version (PFS-12). Breast cancer survivors were classified (i.e., none, mild, moderate, or severe fatigue) based on the cut-scores, and relationships between these cut-scores and decrements in health-related quality of life (HRQOL) were examined. METHODS: A total of 857 breast cancer survivors, stages in situ-IIIa, from the Health, Eating, Activity, and Lifestyle (HEAL) Study were eligible. Survivors completed the PFS-R, SF-36, and a sexual health scale approximately 3 years after diagnosis. Multivariate analysis of covariance was used to examine five fatigue severity cut-score models, controlling for demographics, clinical characteristics, comorbidity, and antidepressant use. Multivariate regression was used to examine HRQOL decrements by cut-score category. RESULTS: Analyses supported two similar fatigue severity cut-score models for the PFS-R and PFS-12: Model A.) none (0), mild (1-3), moderate (4-6), and severe (7-10); and Model D.) none (0), mild (1-2), moderate (3-5), and severe (6-10). For every threshold increase in fatigue severity, clinically meaningful decrements in physical, mental, and sexual health scores were observed, supporting construct validity of the fatigue cut-scores. CONCLUSION: Standardized fatigue cut-scores may enhance interpretability and comparability across studies and populations and guide treating planning.

Reproducibility of physical activity recall over fifteen years: longitudinal evidence from the CARDIA study.

BACKGROUND: To examine the benefits of physical activity (PA) on diseases with a long developmental period, it is important to determine reliability of long-term PA recall. METHODS: We investigated 15-year reproducibility of PA recall. Participants were 3605 White and African-American adults in the Coronary Artery Risk Development in Young Adults study, aged 33-45 at the time of recall assessment. Categorical questions assessed PA before and during high school (HS) and overall PA level at Baseline, with the same timeframes recalled 15 years later. Moderate- and vigorous-intensity scores were calculated from reported months of participation in specific activities. RESULTS: HS PA recall had higher reproducibility than overall PA recall (weighted kappa = 0.43 vs. 0.21). Correlations between 15-year recall and Baseline reports of PA were r = 0.29 for moderate-intensity scores, and r = 0.50 for vigorous-intensity. Recall of vigorous activities had higher reproducibility than moderate-intensity activities. Regardless of number of months originally reported for specific activities, most participants recalled either no activity or activity during all 12 months. CONCLUSION: PA recall from the distant past is moderately reproducible, but poor at the individual level, among young and middle aged adults.

The roles of support seeking and race/ethnicity in posttraumatic growth among breast cancer survivors.

Posttraumatic growth (PTG) after cancer can minimize the emotional impact of disease and treatment; however, the facilitators of PTG, including support seeking, are unclear. The authors examined the role of support seeking on PTG among 604 breast cancer survivors ages 40 to 64 from the Health Eating, Activity, and Lifestyle (HEAL) Study. Multivariable linear regression was used to examine predictors of support seeking (participation in support groups and confiding in health care providers) as well as the relationship between support seeking and PTG. Support program participation was moderate (61.1%) compared to the high rates of confiding in health professionals (88.6%), and African Americans were less likely to report participating than non-Hispanic Whites (odds ratio = .14, confidence intervals [0.08, 0.23]). The mean (SD) PTG score was 48.8 (27.4) (range 0-105). Support program participation (ß = 10.4) and confiding in health care providers (ß = 12.9) were associated (p < .001) with higher PTG. In analyses stratified by race/ethnicity, PTG was significantly higher in non-Hispanic Whites and African American support program participants (p < .01), but not significantly higher in Hispanics/Latinas. Confiding in a health care provider was only associated with PTG for non-Hispanic Whites (p = .02). Support program experiences and patient-provider encounters should be examined to determine which attributes facilitate PTG in diverse populations.

Annual Report to the Nation on the status of cancer, 1975-2008, featuring cancers associated with excess weight and lack of sufficient physical activity.

BACKGROUND: Annual updates on cancer occurrence and trends in the United States are provided through collaboration between the American Cancer Society (ACS), the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), and the North American Association of Central Cancer Registries (NAACCR). This year's report highlights the increased cancer risk associated with excess weight (overweight or obesity) and lack of sufficient physical activity (<150 minutes of physical activity per week). METHODS: Data on cancer incidence were obtained from the CDC, NCI, and NAACCR; data on cancer deaths were obtained from the CDC's National Center for Health Statistics. Annual percent changes in incidence and death rates (age-standardized to the 2000 US population) for all cancers combined and for the leading cancers among men and among women were estimated by joinpoint analysis of long-term trends (incidence for 1992-2008 and mortality for 1975-2008) and short-term trends (1999-2008). Information was obtained from national surveys about the proportion of US children, adolescents, and adults who are overweight, obese, insufficiently physically active, or physically inactive. RESULTS: Death rates from all cancers combined decreased from 1999 to 2008, continuing a decline that began in the early 1990s, among men and among women in most racial and ethnic groups. Death rates decreased from 1999 to 2008 for most cancer sites, including the 4 most common cancers (lung, colorectum, breast, and prostate). The incidence of prostate and colorectal cancers also decreased from 1999 to 2008. Lung cancer incidence declined from 1999 to 2008 among men and from 2004 to 2008 among women. Breast cancer incidence decreased from 1999 to 2004 but was stable from 2004 to 2008. Incidence increased for several cancers, including pancreas, kidney, and adenocarcinoma of the esophagus, which are associated with excess weight. CONCLUSIONS: Although improvements are reported in the US cancer burden, excess weight and lack of sufficient physical activity contribute to the increased incidence of many cancers, adversely affect quality of life for cancer survivors, and may worsen prognosis for several cancers. The current report highlights the importance of efforts to promote healthy weight and sufficient physical activity in reducing the cancer burden in the United States.

The Piper Fatigue Scale-12 (PFS-12): psychometric findings and item reduction in a cohort of breast cancer survivors.

Brief, valid measures of fatigue, a prevalent and distressing cancer symptom, are needed for use in research. This study's primary aim was to create a shortened version of the revised Piper Fatigue Scale (PFS-R) based on data from a diverse cohort of breast cancer survivors. A secondary aim was to determine whether the PFS captured multiple distinct aspects of fatigue (a multidimensional model) or a single overall fatigue factor (a unidimensional model). Breast cancer survivors (n = 799; stages in situ through IIIa; ages 29-86 years) were recruited through three SEER registries (New Mexico, Western Washington, and Los Angeles, CA) as part of the Health, Eating, Activity, and Lifestyle (HEAL) study. Fatigue was measured approximately 3 years post-diagnosis using the 22-item PFS-R that has four subscales (Behavior, Affect, Sensory, and Cognition). Confirmatory factor analysis was used to compare unidimensional and multidimensional models. Six criteria were used to make item selections to shorten the PFS-R: scale's content validity, items' relationship with fatigue, content redundancy, differential item functioning by race and/or education, scale reliability, and literacy demand. Factor analyses supported the original 4-factor structure. There was also evidence from the bi-factor model for a dominant underlying fatigue factor. Six items tested positive for differential item functioning between African-American and Caucasian survivors. Four additional items either showed poor association, local dependence, or content validity concerns. After removing these 10 items, the reliability of the PFS-12 subscales ranged from 0.87 to 0.89, compared to 0.90-0.94 prior to item removal. The newly developed PFS-12 can be used to assess fatigue in African-American and Caucasian breast cancer survivors and reduces response burden without compromising reliability or validity. This is the first study to determine PFS literacy demand and to compare PFS-R responses in African-Americans and Caucasian breast cancer survivors. Further testing in diverse populations is warranted.

DEXA measures of body fat percentage and acute phase proteins among breast cancer survivors: a cross-sectional analysis.

BACKGROUND: C-reactive protein (CRP) and Serum amyloid A protein (SAA) increases with systemic inflammation and are related to worse survival for breast cancer survivors. This study examines the association between percent body fat and SAA and CRP and the potential interaction with NSAID use and weight change. METHODS: Participants included 134 non-Hispanic white and Hispanic breast cancer survivors from the Health, Eating, Activity, and Lifestyle Study. Body fat percentage, measured with Dual Energy X-ray Absorptiometer (DEXA), and circulating levels of CRP and SAA were obtained 30 months after breast cancer diagnosis. RESULTS: Circulating concentrations of CRP and SAA were associated with increased adiposity as measured by DEXA after adjustment for age at 24-months, race/ethnicity, dietary energy intake, weight change, and NSAID use. Survivors with higher body fat ≥35% had significantly higher concentrations of CRP (2.01 mg/l vs. 0.85 mg/l) and SAA (6.21 mg/l vs. 4.21 mg/l) compared to non-obese (body fat < 35%). Women who had gained more than 5% of their body weight since breast cancer diagnosis had non-statistically significant higher geometric mean levels of CRP and SAA. Mean levels of CRP and SAA were higher among obese women who were non-users of NSAIDs compared to current users; the association with SAA reached statistical significance (Mean SAA = 7.24, 95%CI 6.13-8.56 for non-NSAID; vs. 4.87; 95%CI 3.95-6.0 for NSAID users respectively). CONCLUSIONS: Breast cancer survivors with higher body fat had higher mean concentrations of CRP and SAA than women with lower body fat. Further assessment of NSAID use and weight control in reducing circulating inflammatory markers among survivors may be worthwhile to investigate in randomized intervention trials as higher inflammatory markers are associated with worse survival.