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This paper describes the ethnic and socioeconomic correlates of functioning in a cohort of long-term nonrecurring breast cancer survivors. Participants (n = 804) in this study were women from the Health, Eating, Activity, and Lifestyle (HEAL) Study, a population-based, multicenter, multiethnic, prospective study of women newly diagnosed with in situ or Stages I to IIIA breast cancer. Measurements occurred at three timepoints following diagnosis. Outcomes included standardized measures of functioning (MOS SF-36). Overall, these long-term survivors reported values on two physical function subscales of the SF-36 slightly lower than population norms. Black women reported statistically significantly lower physical functioning (PF) scores (P = 0.01), compared with White and Hispanic women, but higher mental health (MH) scores (P < 0.01) compared with White and Hispanic women. In the final adjusted model, race was significantly related to PF, with Black participants and participants in the \"Other\" ethnic category reporting poorer functioning compared to the White referent group (P < 0.01, 0.05). Not working outside the home, being retired or disabled and being unemployed (on leave, looking for work) were associated with poorer PF compared to currently working (both P < 0.01). These data indicate that race/ethnicity influences psychosocial functioning in breast cancer survivors and can be used to identify need for targeted interventions to improve functioning.

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. 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. 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.

Purpose This study aimed to determine the prevalence of sarcopenia and examine whether sarcopenia was associated with overall and breast-cancer-specific mortality in a cohort of women diagnosed with breast cancer (stages I–IIIA). Methods A total of 471 breast cancer patients from western Washington State and New Mexico who participated in the prospective Health, Eating, Activity, and Lifestyle Study were included in this study. Appendicular lean mass was measured using dual X-ray absorptiometry scans at study inception, on average, 12 months after diagnosis. Sarcopenia was defined as two standard deviations below the young healthy adult female mean of appendicular lean mass divided by height squared (<5.45 kg/m 2 ). Total and breast-cancer-specific mortality data were obtained from Surveillance Epidemiology and End Results registries. Multivariable Cox proportional hazard models assessed the associations between sarcopenia and mortality. Results Median follow-up was 9.2 years; 75 women were classified as sarcopenic, and among 92 deaths, 46 were attributed to breast cancer. In multivariable models that included age, race-ethnicity/study site, treatment type, comorbidities, waist circumference, and total body fat percentage, sarcopenia was independently associated with overall mortality (hazard ratio (HR) = 2.86; 95 % CI, 1.67–4.89). Sarcopenic women had increased risk of breast-cancer-specific mortality, although the association was not statistically significant (HR = 1.95, 95 % CI, 0.87–4.35). Conclusion Sarcopenia is associated with an increased risk of overall mortality in breast cancer survivors and may be associated with breast-cancer-specific mortality. The development of effective interventions to maintain and/or increase skeletal muscle mass to improve prognosis in breast cancer survivors warrants further study. Implications for Cancer Survivors Such interventions may help breast cancer patients live longer.

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.

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/m²), overweight (25–29.9 kg/m²), and obese (≥30 kg/m²). 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.

The relationships among breast density, age, and use of hormone replacement therapy (HRT) in breast cancer detection have not been fully evaluated. To determine how breast density, age, and use of HRT individually and in combination affect the accuracy of screening mammography. Prospective cohort study. 7 population-based mammography registries in North Carolina; New Mexico; New Hampshire; Vermont; Colorado; Seattle, Washington; and San Francisco, California. 329 495 women 40 to 89 years of age who had 463 372 screening mammograms from 1996 to 1998; 2223 women received a diagnosis of breast cancer. Breast density, age, HRT use, rate of breast cancer occurrence, and sensitivity and specificity of screening mammography. Adjusted sensitivity ranged from 62.9% in women with extremely dense breasts to 87.0% in women with almost entirely fatty breasts; adjusted sensitivity increased with age from 68.6% in women 40 to 44 years of age to 83.3% in women 80 to 89 years of age. Adjusted specificity increased from 89.1% in women with extremely dense breasts to 96.9% in women with almost entirely fatty breasts. In women who did not use HRT, adjusted specificity increased from 91.4% in women 40 to 44 years of age to 94.4% in women 80 to 89 years of age. In women who used HRT, adjusted specificity was about 91.7% for all ages. Mammographic breast density and age are important predictors of the accuracy of screening mammography. Although HRT use is not an independent predictor of accuracy, it probably affects accuracy by increasing breast density.

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.

Objective: To investigate, among women with breast cancer, how postdiagnosis diet quality and the combination of diet quality and recreational physical activity are associated with prognosis. Methods: This multiethnic, prospective observational cohort included 670 women diagnosed with local or regional breast cancer. Thirty months after diagnosis, women completed self-report assessments on diet and physical activity and were followed for 6 years. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals for death from any cause and breast cancer death. Results: Women consuming better-quality diets, as defined by higher Healthy Eating Index-2005 scores, had a 60% reduced risk of death from any cause (HR Q4:Q1 : 0.40,95% CI: 0.17, 0.94) and an 88% reduced risk of death from breast cancer (HR Q4:Q1 : 0.12, 95% CI: 0.02, 0.99). Compared with inactive survivors consuming poor-quality diets, survivors engaging in any recreational physical activity and consuming better-quality diets had an 89% reduced risk of death from any cause (HR: 0.11,95% CI: 0.04, 0.36) and a 91% reduced risk of death from breast cancer (HR: 0.09, 95% CI: 0.01, 0.89). Associations observed were independent of obesity status. Conclusion: Women diagnosed with localized or regional breast cancer may improve prognosis by adopting betterquality dietary patterns and regular recreational physical activity. Lifestyle interventions emphasizing postdiagnosis behavior changes are advisable in breast cancer survivors.

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 (HR q4:q1 : 2.99, 95 % CI 1.14, 7.86) but its positive association with breast cancer-specific mortality was not statistically significant (HR q4:q1 : 2.69, 95 % CI 0.69, 12.01). WHR was positively associated with all-cause mortality (HR q4:q1 : 2.10, 95 % CI 1.08, 4.05) and breast cancer-specific mortality (HR q4: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.

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.