The American Cancer Society challenge goal to reduce US cancer mortality by 50% between 1990 and 2015: Results and reflections.

In 1996, the Board of Directors of the American Cancer Society (ACS) challenged the United States to reduce what looked to be possible peak cancer mortality in 1990 by 50% by the year 2015. This analysis examines the trends in cancer mortality across this 25-year challenge period from 1990 to 2015. In 2015, cancer death rates were 26% lower than in 1990 (32% lower among men and 22% lower among women). The 50% reduction goal was more fully met for the cancer sites for which there was enactment of effective approaches for prevention, early detection, and/or treatment. Among men, mortality rates dropped for lung cancer by 45%, for colorectal cancer by 47%, and for prostate cancer by 53%. Among women, mortality rates dropped for lung cancer by 8%, for colorectal cancer by 44%, and for breast cancer by 39%. Declines in the death rates of all other cancer sites were substantially smaller (13% among men and 17% among women). The major factors that accounted for these favorable trends were progress in tobacco control and improvements in early detection and treatment. As we embark on new national cancer goals, this recent past experience should teach us that curing the cancer problem will require 2 sets of actions: making new discoveries in cancer therapeutics and more completely applying those discoveries in cancer prevention we have already made. CA Cancer J Clin 2016;66:359-369. © 2016 American Cancer Society.

Nutrition and physical activity guidelines for cancer survivors.

Cancer survivors are often highly motivated to seek information about food choices, physical activity, and dietary supplements to improve their treatment outcomes, quality of life, and overall survival. To address these concerns, the American Cancer Society (ACS) convened a group of experts in nutrition, physical activity, and cancer survivorship to evaluate the scientific evidence and best clinical practices related to optimal nutrition and physical activity after the diagnosis of cancer. This report summarizes their findings and is intended to present health care providers with the best possible information with which to help cancer survivors and their families make informed choices related to nutrition and physical activity. The report discusses nutrition and physical activity guidelines during the continuum of cancer care, briefly highlighting important issues during cancer treatment and for patients with advanced cancer, but focusing largely on the needs of the population of individuals who are disease free or who have stable disease following their recovery from treatment. It also discusses select nutrition and physical activity issues such as body weight, food choices, food safety, and dietary supplements; issues related to selected cancer sites; and common questions about diet, physical activity, and cancer survivorship.

Impact of a behavioral weight loss intervention on comorbidities in overweight and obese breast cancer survivors.

PURPOSE: Comorbid medical conditions are common among breast cancer survivors, contribute to poorer long-term survival and increased overall mortality, and may be ameliorated by weight loss. This secondary analysis evaluated the impact of a weight loss intervention on comorbid medical conditions immediately following an intervention (12 months) and 1-year postintervention (24 months) using data from the Exercise and Nutrition to Enhance Recovery and Good health for You (ENERGY) trial-a phase III trial which was aimed at and successfully promoted weight loss. METHODS: ENERGY randomized 692 overweight/obese women who had completed treatment for early stage breast cancer to either a 1-year group-based behavioral intervention designed to achieve and maintain weight loss or to a less intensive control intervention. Minimal support was provided postintervention. New medical conditions, medical conditions in which non-cancer medications were prescribed, hospitalizations, and emergency room visits, were compared at baseline, year 1, and year 2. Changes over time were analyzed using chi-squared tests, Kaplan-Meier, and logistic regression analyses. RESULTS: At 12 months, women randomized to the intervention had fewer new medical conditions compared to the control group (19.6 vs. 32.2 %, p < 0.001); however, by 24 months, there was no longer a significant difference. No difference was observed in each of the four conditions for which non-cancer medications were prescribed, hospital visits, or emergency visits at either 12 or 24 months. CONCLUSIONS: These results support a short-term benefit of modest weight loss on the likelihood of comorbid conditions; however, recidivism and weight regain likely explain no benefit at 1-year postintervention follow-up.

Project TEACH: A Capacity-Building Training Program for Community-Based Organizations and Public Health Agencies.

Project TEACH (Teaching Equity to Advance Community Health) is a capacity-building training program to empower community-based organizations and regional public health agencies to develop data-driven, evidence-based, outcomes-focused public health interventions. TEACH delivers training modules on topics such as logic models, health data, social determinants of health, evidence-based interventions, and program evaluation. Cohorts of 7 to 12 community-based organizations and regional public health agencies in each of the 6 Colorado Area Health Education Centers service areas participate in a 2-day training program tailored to their specific needs. From July 2008 to December 2011, TEACH trained 94 organizations and agencies across Colorado. Training modules were well received and resulted in significant improvement in knowledge in core content areas, as well as accomplishment of self-proposed organizational goals, grant applications/awards, and several community-academic partnerships.

Quality of life outcomes from the Exercise and Nutrition Enhance Recovery and Good Health for You (ENERGY)-randomized weight loss trial among breast cancer survivors.

Obesity is a poor prognostic factor and is negatively related to quality of life (QOL) in breast cancer survivors. Exercise and Nutrition to Enhance Recovery and Good Health for You is the largest weight loss trial completed among cancer survivors. Percent losses in body weight with an intensive group-based intervention versus an attention control were 6.0 versus 1.5 % (p < 0.0001) and 3.7 versus 1.3 % (p < 0.0001) at 12 and 24 months, respectively. ENERGY also was designed to answer the research question: Does weight loss significantly improve vitality and physical function (key components of QOL)? 692 breast cancer survivors (BMI: 25-45 kg/m(2)) at 4 US sites were randomized to a year-long intensive intervention of 52 group sessions and telephone counseling contacts versus a non-intensive (control) of two in-person counseling sessions. Weight, self-reported QOL, and symptoms were measured semi-annually for two years. Significant decreases in physical function and increases in symptoms were observed among controls from baseline to 6 months, but not in the intervention arm, -3.45 (95 % Confidence Interval [CI] -6.10, -0.79, p = 0.0109) and 0.10 (95 %CI 0.04, 0.16, p = 0.0021), respectively. Improvements in vitality were seen in both arms but trended toward greater improvement in the intervention arm -2.72 (95 % CI -5.45, 0.01, p = 0.0508). These differences diminished over time; however, depressive symptoms increased in the intervention versus control arms and became significant at 24 months, -1.64 (95 % CI -3.13, -0.15, p = 0.0308). Increased QOL has been reported in shorter term diet and exercise trials among cancer survivors. These longer term data suggest that diet and exercise interventions improve some aspects of QOL, but these benefits may diminish over time.

Lack of significant association between serum inflammatory cytokine profiles and the presence of colorectal adenoma.

BACKGROUND: Inflammatory cytokines in the colonic microenvironment have been shown to increase with advance colorectal cancer disease state. However, the contribution of inflammatory cytokines to pre-malignant disease, such as the formation of adenomas, is unclear. METHODS: Using the Milliplex® MAP Human Cytokine/ Chemokine Magnetic Bead Panel Immunoassay, serum cytokine and chemokine profiles were assayed among participants without an adenoma (n = 97) and those with an adenoma (n = 97) enrolled in the NCI-funded Insulin Resistance Atherosclerosis Colon Study. The concentrations of interleukin-10 (IL-10), IL-1ß, IL-6, IL-17A, IL-2, IL-4, IL-7, IL-12(p70), interferon-γ (IFN-γ), macrophage chemoattractant protein-1 (MCP-1), regulated on activation, normal T cell expressed and secreted (RANTES), tumor necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF), granulocyte macrophage colony-stimulating factor (GM-CSF), and macrophage inflammatory protein-1ß (MIP-1ß) were determined. Multiple logistic regression analyses were used to evaluate the association between adenoma prevalence and cytokine levels. RESULTS: The presence of colorectal adenomas was not associated with significant increases in the systemic levels of proinflammatory (TNF-α, IL-6, IL-1ß) or T-cell polarizing (IL-12, IL-2, IL-10, IL-4, IL-17, IFN-γ) cytokines. Furthermore, MCP-1 and RANTES levels were equivalent in the serum of study participants with and without adenomas. CONCLUSIONS: These findings suggest colorectal adenoma prevalence may not be associated with significant alterations in systemic inflammation.

Predicting arsenic concentrations in groundwater of San Luis Valley, Colorado: implications for individual-level lifetime exposure assessment.

Consumption of inorganic arsenic in drinking water at high levels has been associated with chronic diseases. Risk is less clear at lower levels of arsenic, in part due to difficulties in estimating exposure. Herein we characterize spatial and temporal variability of arsenic concentrations and develop models for predicting aquifer arsenic concentrations in the San Luis Valley, Colorado, an area of moderately elevated arsenic in groundwater. This study included historical water samples with total arsenic concentrations from 595 unique well locations. A longitudinal analysis established temporal stability in arsenic levels in individual wells. The mean arsenic levels for a random sample of 535 wells were incorporated into five kriging models to predict groundwater arsenic concentrations at any point in time. A separate validation dataset (n = 60 wells) was used to identify the model with strongest predictability. Findings indicate that arsenic concentrations are temporally stable (r = 0.88; 95 % CI 0.83-0.92 for samples collected from the same well 15-25 years apart) and the spatial model created using ordinary kriging best predicted arsenic concentrations (ρ = 0.72 between predicted and observed validation data). These findings illustrate the value of geostatistical modeling of arsenic and suggest the San Luis Valley is a good region for conducting epidemiologic studies of groundwater metals because of the ability to accurately predict variation in groundwater arsenic concentrations.

A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010.

BACKGROUND: Quantification of the disease burden caused by different risks informs prevention by providing an account of health loss different to that provided by a disease-by-disease analysis. No complete revision of global disease burden caused by risk factors has been done since a comparative risk assessment in 2000, and no previous analysis has assessed changes in burden attributable to risk factors over time. METHODS: We estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010. We estimated exposure distributions for each year, region, sex, and age group, and relative risks per unit of exposure by systematically reviewing and synthesising published and unpublished data. We used these estimates, together with estimates of cause-specific deaths and DALYs from the Global Burden of Disease Study 2010, to calculate the burden attributable to each risk factor exposure compared with the theoretical-minimum-risk exposure. We incorporated uncertainty in disease burden, relative risks, and exposures into our estimates of attributable burden. FINDINGS: In 2010, the three leading risk factors for global disease burden were high blood pressure (7·0% [95% uncertainty interval 6·2-7·7] of global DALYs), tobacco smoking including second-hand smoke (6·3% [5·5-7·0]), and alcohol use (5·5% [5·0-5·9]). In 1990, the leading risks were childhood underweight (7·9% [6·8-9·4]), household air pollution from solid fuels (HAP; 7·0% [5·6-8·3]), and tobacco smoking including second-hand smoke (6·1% [5·4-6·8]). Dietary risk factors and physical inactivity collectively accounted for 10·0% (95% UI 9·2-10·8) of global DALYs in 2010, with the most prominent dietary risks being diets low in fruits and those high in sodium. Several risks that primarily affect childhood communicable diseases, including unimproved water and sanitation and childhood micronutrient deficiencies, fell in rank between 1990 and 2010, with unimproved water and sanitation accounting for 0·9% (0·4-1·6) of global DALYs in 2010. However, in most of sub-Saharan Africa childhood underweight, HAP, and non-exclusive and discontinued breastfeeding were the leading risks in 2010, while HAP was the leading risk in south Asia. The leading risk factor in Eastern Europe, most of Latin America, and southern sub-Saharan Africa in 2010 was alcohol use; in most of Asia, North Africa and Middle East, and central Europe it was high blood pressure. Despite declines, tobacco smoking including second-hand smoke remained the leading risk in high-income north America and western Europe. High body-mass index has increased globally and it is the leading risk in Australasia and southern Latin America, and also ranks high in other high-income regions, North Africa and Middle East, and Oceania. INTERPRETATION: Worldwide, the contribution of different risk factors to disease burden has changed substantially, with a shift away from risks for communicable diseases in children towards those for non-communicable diseases in adults. These changes are related to the ageing population, decreased mortality among children younger than 5 years, changes in cause-of-death composition, and changes in risk factor exposures. New evidence has led to changes in the magnitude of key risks including unimproved water and sanitation, vitamin A and zinc deficiencies, and ambient particulate matter pollution. The extent to which the epidemiological shift has occurred and what the leading risks currently are varies greatly across regions. In much of sub-Saharan Africa, the leading risks are still those associated with poverty and those that affect children. FUNDING: Bill & Melinda Gates Foundation.

Long-term weight gain among Hispanic and non-Hispanic White women with and without breast cancer.

Weight gain following breast cancer diagnosis is common, but limited data exists on whether this gain is in excess of that gained during normal aging. This study investigated weight patterns among women with and without breast cancer to determine the effects of the breast cancer experience on weight change. Using the SHINE 4-Corners Breast Cancer Study, 305 women with breast cancer and 345 women without were followed prospectively. Weight change of ≥5% was defined as the difference between the self-reported weight measurements obtained at breast cancer diagnosis (or referent date for women without breast cancer) and about 6 yr later. Multiple logistic regression analyses were used. Within this cohort, 60% of women were overweight or obese and 37% of women gained weight. No significant greater weight gain was observed between women with vs. without breast cancer [adjusted odds ratio (ORadj) = 1.15, 95% CI 0.79-1.68] or between Hispanic vs. non-Hispanic White women (ORadj = 1.09, 95% CI 0.72-1.66) after adjustment. Weight gain was associated with being younger and having a lower body mass index. Among breast cancer survivors, cancer treatment factors were not associated with weight gain. These results suggest that weight management approaches are needed, especially those targeted to at-risk populations such as breast cancer survivors.

A case-cohort study examining lifetime exposure to inorganic arsenic in drinking water and diabetes mellitus.

BACKGROUND: Consumption of drinking water with high levels of inorganic arsenic (over 500 µg/L) has been associated with type II diabetes mellitus (DM), but previous studies have been inconclusive about risks at lower levels (<100 µg/L). We present a case-cohort study based on individual estimates of lifetime arsenic exposure to examine the relationship between chronic low-level arsenic exposure and risk of DM. METHODS: This case-cohort study included 141 cases of DM diagnosed between 1984 and 1998 as part of the prospective San Luis Valley Diabetes Study. A comparison sub-cohort of 488 participants was randomly sampled from 936 eligible participants who were disease free at baseline. Individual lifetime arsenic exposure estimates were determined using a methodology that incorporates the use of a structured interview to determine lifetime residence and employment history, geospatial modeling of arsenic concentrations in drinking water, and urine arsenic concentrations. A Cox proportional hazards model with known DM risk factors as time-dependent covariates was used to assess the association between lifetime exposure to inorganic arsenic in drinking water and incident DM. RESULTS: Our findings show a significant association between inorganic arsenic exposure and DM risk (hazard ratio [HR]=1.27, 95%=1.01, 1.59 per 15 µg/L) while adjusting for ethnicity and time varying covariates age, body mass index and physical activity level. CONCLUSIONS: Exposure to low-level inorganic arsenic in drinking water is associated with increased risk for type II DM in this population based on a comprehensive lifetime exposure assessment.

Sex-specific association of sequence variants in CBS and MTRR with risk for promoter hypermethylation in the lung epithelium of smokers.

Gene promoter hypermethylation is now regarded as a promising biomarker for the risk and progression of lung cancer. The one-carbon metabolism pathway is postulated to affect deoxyribonucleic acid (DNA) methylation because it is responsible for the generation of S-adenosylmethionine (SAM), the methyl donor for cellular methylation reactions. This study investigated the association of single nucleotide polymorphisms (SNPs) in six one-carbon metabolism-related genes with promoter hypermethylation in sputum DNA from non-Hispanic white smokers in the Lovelace Smokers Cohort (LSC) (n = 907). Logistic regression was used to assess the association of SNPs with hypermethylation using a high/low methylation cutoff. SNPs in the cystathionine beta synthase (CBS) and 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) genes were significantly associated with high methylation in males [CBS rs2850146 (-8283G > C), OR = 4.9; 95% CI: 1.98, 12.2, P = 0.0006] and low methylation in females [MTRR rs3776467 (7068A > G), OR = 0.57, 95% CI: 0.42, 0.77, P = 0.0003]. The variant allele of rs2850146 was associated with reduced gene expression and increased plasma homocysteine (Hcy) concentrations. Three plasma metabolites, Hcy, methionine and dimethylglycine, were associated with increased risk for gene methylation. These studies suggest that SNPs in CBS and MTRR have sex-specific associations with aberrant methylation in the lung epithelium of smokers that could be mediated by the affected one-carbon metabolism and transsulfuration in the cells.

Increase in circulating levels of IGF-1 and IGF-1/IGFBP-3 molar ratio over a decade is associated with colorectal adenomatous polyps.

High levels of circulating insulin-like growth factor-1 (IGF-1) have been associated with increased risk of several cancers. Regarding colorectal cancer, these associations are generally weak. We hypothesized that an increase in IGF-1 over time would be a stronger risk factor for cancer-related outcomes than the actual levels. In this analysis we utilized existing data from the Insulin Resistance and Atherosclerosis Study (IRAS). Circulating IGF-1 levels and molar ratios of IGF-1 to IGF binding protein 3 (IGFBP-3) were measured at three time points, within a 10-year follow-up period. We examined the associations of increase of the two variables with the presence of colorectal adenoma at the end of follow-up among participants with normal glucose tolerance at baseline. This included 143 individuals, from which 24 were diagnosed with adenomatous polyps. Although the mean levels of IGF-1 and IGF-1/IGFBP-3 decline with age, ~ 30% of the participants showed an increase of at least fifteen percent ("ever increase") in one or both of these variables, compared to baseline. We found a positive association between "ever increase" in IGF-1 or IGF-1/IGFBP-3 and the presence of colorectal adenoma: ORs were 3.81 (95% CI: 1.30-10.8) and 2.83 (95% CI: 1.00-8.22), respectively. No association was found when analyzing the actual levels of both variables at any time point. Our data suggest that an increase in circulating IGF-1 or IGF-1/IGFBP-3 may represent a disturbed GH/IGF1 homeostasis, which could favor the development of precancerous lesions such as colorectal adenoma.

Behavioral risk factors and their relationship to tumor characteristics in Hispanic and non-Hispanic white long-term breast cancer survivors.

Hispanics are more likely to be diagnosed with breast cancer at a younger age, with more advanced stage at diagnosis, hormone receptor-negative tumors, and worse prognosis than non-Hispanic whites (NHW). Little is known regarding the association between behavioral risk factors and breast tumor characteristics and whether these associations vary by race/ethnicity. We evaluated the association between several behavioral risk factors and tumor phenotype in a population-based study of Hispanics and NHWs. Participants are cases (846 Hispanic and 1,625 NHW women) diagnosed with breast cancer between 1999 and 2004 in Arizona, Colorado, New Mexico, or Utah. The association between breast cancer characteristics and obesity, physical activity, smoking, alcohol intake, and reproductive factors was examined. Logistic regression was used to compute the ethnic-specific odds ratios for the association between these risk factors and estrogen receptor (ER) status, tumor size, and histologic grade. Hispanics had more ER-negative tumors (28 vs. 20%), tumors >2 cm (39 vs. 27%), and poorly differentiated tumors (84 vs. 77%) than NHW. Among premenopausal women, obesity was associated with more ER-negative cancers among NHW [OR = 2.47 (95% CI: 1.08, 5.67)] but less ER-negative cancers among Hispanics [OR = 0.29 (0.13, 0.66)]. Obesity was associated with larger tumors among NHW [OR = 1.58 (1.09, 2.29)], but not among Hispanics. Never using mammography was associated with larger tumors in both ethnic groups. Moderate alcohol drinking and moderate and vigorous physical activity were weakly associated with smaller tumors in both ethnic groups. Our findings suggest that the association of obesity and other behavioral risk factors with breast cancer characteristics differ by ethnicity. We observed a divergent pattern between Hispanic and NHW cases in the association between obesity and ER status and tumor size. These observations suggest that a complex set of metabolic and hormonal factors related to estrogen and insulin pathways influence tumor characteristics.

Vitamin D intake, vitamin D receptor polymorphisms, and breast cancer risk among women living in the southwestern U.S.

No studies of dietary vitamin D intake and vitamin D receptor (VDR) have been conducted comparing breast risk among Hispanic women and non-Hispanic white (NHW) women. We investigated the association between vitamin D intake and breast cancer in a population-based case-control study of 1,527 NHW and 791 Hispanic breast cancer cases diagnosed in 1999-2004 in Arizona, New Mexico, Utah, and Colorado, and 1,599 NHW and 922 Hispanic age-matched controls. Vitamin D intake was assessed using food frequency questionnaires, and associations with breast cancer were adjusted for age, ethnicity, state, education, body mass index, smoking, age at menarche, age at first birth, parity, hormone exposure, height, and physical activity using logistic regression. BsmI, Poly A and FokI vitamin D receptor (VDR) genotypes were also measured. Dietary vitamin D intake was positively associated with breast cancer (highest vs. lowest quartile (Q (4) vs. Q (1)): odds ratio (OR) = 1.35, 95% confidence interval (CI) = 1.15-1.60; P (trend) = 0.003), whereas vitamin D supplement use was inversely associated with breast cancer (10+ µg/day vs. none: OR = 0.79, 95% CI = 0.65-0.96, P (trend) = 0.01). Similar patterns in risk were observed by ethnicity and menopausal status. Positive associations with dietary vitamin D intake and inverse associations with supplement use were observed for ER+/PR+ and ER-/PR- breast cancers, but not for ER+/PR- disease. BsmI genotype significantly modified the association between dietary vitamin D and breast cancer overall. Future research is needed to better understand potential differences in breast cancer risk by vitamin D source and hormone receptor status.

ADRB2 G-G haplotype associated with breast cancer risk among Hispanic and non-Hispanic white women: interaction with type 2 diabetes and obesity.

INTRODUCTION: Polymorphisms in the beta-2-adrenergic receptor (ADRB2) gene have been studied in relation to risk of type 2 diabetes and obesity, risk factors that have received increased attention in relation to breast cancer. We evaluated the hypothesis that ADRB2 variants (rs1042713, rs1042714) are associated with breast cancer risk in non-Hispanic white (NHW) and Hispanic (H) women using data from a population-based case-control study conducted in the southwestern United States. METHODS: Data on lifestyle and medical history, and blood samples, were collected during in-person interviews for incident primary breast cancer cases (1,244 NHW, 606 H) and controls (1,330 NHW, 728 H). ADRB2 genotypes for rs1042713(G/A) and rs1042714(G/C) were determined using TaqMan assays. The associations of each variant and corresponding haplotypes with breast cancer were estimated using multivariable logistic regression. RESULTS: Two copies compared to one or zero copies of the ADRB2 G-G haplotype were associated with increased breast cancer risk for NHW women [odds ratio (OR), 1.95; 95 % confidence interval (95 % CI), 1.26-3.01], but with reduced risk for H women [OR, 0.74; 95 % CI, 0.50-1.09]. Effect estimates were strengthened for women with a body mass index (BMI) ≥25 kg/m(2) [H: OR, 0.50; 95 % CI, 0.31-0.82; NHW: OR, 3.85; 95 % CI, 1.88-7.88] and for H women with a history of diabetes [H: OR, 0.32; 95 % CI, 0.12-0.89]. CONCLUSIONS: These data suggest that ethnicity modifies the association between the ADRB2 G-G haplotype and breast cancer risk, and being overweight or obese enhances the divergence of risk between H and NHW women.

Effect of community affluence on the association between individual socioeconomic status and cardiovascular disease risk factors, Colorado, 2007-2008.

We assessed the hypothesis that community affluence modifies the association between individual socioeconomic status (SES) and 6 cardiovascular disease (CVD) risk factors: diabetes, hypertension, physical inactivity, obesity, smoking, and poor nutrition. We stratified data from the Colorado Behavioral Risk Factor Surveillance System for 2007 and 2008 by individual SES and 3 categories of community affluence (median household income of county). People who had a low SES seemed to benefit from residing in high-affluence communities. Living in high-affluence communities may mitigate the effect of poverty on CVD risk factors; our findings support the value of interventions that address social determinants of health.

Benefits and harms of CT screening for lung cancer: a systematic review.

CONTEXT: Lung cancer is the leading cause of cancer death. Most patients are diagnosed with advanced disease, resulting in a very low 5-year survival. Screening may reduce the risk of death from lung cancer. OBJECTIVE: To conduct a systematic review of the evidence regarding the benefits and harms of lung cancer screening using low-dose computed tomography (LDCT). A multisociety collaborative initiative (involving the American Cancer Society, American College of Chest Physicians, American Society of Clinical Oncology, and National Comprehensive Cancer Network) was undertaken to create the foundation for development of an evidence-based clinical guideline. DATA SOURCES: MEDLINE (Ovid: January 1996 to April 2012), EMBASE (Ovid: January 1996 to April 2012), and the Cochrane Library (April 2012). STUDY SELECTION: Of 591 citations identified and reviewed, 8 randomized trials and 13 cohort studies of LDCT screening met criteria for inclusion. Primary outcomes were lung cancer mortality and all-cause mortality, and secondary outcomes included nodule detection, invasive procedures, follow-up tests, and smoking cessation. DATA EXTRACTION: Critical appraisal using predefined criteria was conducted on individual studies and the overall body of evidence. Differences in data extracted by reviewers were adjudicated by consensus. RESULTS: Three randomized studies provided evidence on the effect of LDCT screening on lung cancer mortality, of which the National Lung Screening Trial was the most informative, demonstrating that among 53,454 participants enrolled, screening resulted in significantly fewer lung cancer deaths (356 vs 443 deaths; lung cancer−specific mortality, 274 vs 309 events per 100,000 person-years for LDCT and control groups, respectively; relative risk, 0.80; 95% CI, 0.73-0.93; absolute risk reduction, 0.33%; P = .004). The other 2 smaller studies showed no such benefit. In terms of potential harms of LDCT screening, across all trials and cohorts, approximately 20% of individuals in each round of screening had positive results requiring some degree of follow-up, while approximately 1% had lung cancer. There was marked heterogeneity in this finding and in the frequency of follow-up investigations, biopsies, and percentage of surgical procedures performed in patients with benign lesions. Major complications in those with benign conditions were rare. CONCLUSION: Low-dose computed tomography screening may benefit individuals at an increased risk for lung cancer, but uncertainty exists about the potential harms of screening and the generalizability of results.

Cardiovascular disease competes with breast cancer as the leading cause of death for older females diagnosed with breast cancer: a retrospective cohort study.

INTRODUCTION: Many women who survive breast cancer die of causes unrelated to their cancer diagnosis. This study was undertaken to assess factors that are related to breast cancer mortality versus mortality from other causes and to describe the leading causes of death among older women diagnosed with breast cancer. METHODS: Women diagnosed with breast cancer at age 66 or older between 1992 and 2000 were identified in the Surveillance, Epidemiology and End Results-Medicare linked database and followed through the end of 2005. RESULTS: A total of 63,566 women diagnosed with breast cancer met the inclusion criteria and were followed for a median of approximately nine years. Almost one-half (48.7%) were alive at the end of follow-up. Ages and comorbidities at the time of diagnosis had the largest effects on mortality from other causes, while tumor stage, tumor grade, estrogen receptor status, age and comorbidities at the time of diagnosis all had effects on breast cancer-specific mortality. Fully adjusted relative hazards of the effects of comorbidities on breast cancer-specific mortality were 1.24 (95% confidence interval (95% CI) 1.13 to 1.26) for cardiovascular disease, 1.13 (95% CI 1.13 to 1.26) for previous cancer, 1.13 (95% CI 1.05 to 1.22) for chronic obstructive pulmonary disease and 1.10 (95% CI 1.03 to 1.16) for diabetes. Among the total study population, cardiovascular disease was the primary cause of death in the study population (15.9% (95% CI 15.6 to 16.2)), followed closely by breast cancer (15.1% (95% CI 14.8 to 15.4)). CONCLUSIONS: Comorbid conditions contribute importantly to both total mortality and breast cancer-specific mortality among breast cancer survivors. Attention to reducing the risk of cardiovascular disease should be a priority for the long-term care of women following the diagnosis and treatment of breast cancer.

Differential expression of prognostic biomarkers between interval and screen-detected breast cancers: does age or family history matter?

The aim of this study was to compare tumor expression of prognostic biomarkers between interval breast cancers and screen-detected breast cancers overall, and according to age at diagnosis and familial risk. Tissue micro-arrays were constructed from 98 breast cancers (47 interval and 51 screen-detected) diagnosed in women in the Cancer Genetics Network. Arrays were immuno-stained to compare protein expression of six biomarkers including estrogen and progesterone receptor (ER/PR), Her2/neu, EGFR, cytokeratin 5/6, and Ki67. Fisher's Exact test was used to compare expression between interval and screen-detected cancers. Interval cancers were larger (P = 0.04), higher stage (P < 0.001), and more likely to have lobular histology (P = 0.01) than screen-detected cancers. Overall, interval cancers more often overexpressed EGFR (P = 0.01) and were somewhat more likely to be ER- (55% vs. 43%, P = 0.3), and triple negative (ER-/PR-/Her2-) (21 vs. 12%, P = 0.26). A greater difference in the proportion of interval versus screen-detected tumors that were ER- (53 vs. 35%; P = 0.29), PR- (35 vs. 21%; P = 0.25) and EGFR+ (17 vs. 0%; P = 0.02) was evident among women over 50. There was a trend toward differential expression among women with familial risk for PR- (P = 0.005) and triple negative status (P = 0.02). This study provides new data indicating that EGFR may be important in the etiology of interval cancer and be a possible therapeutic target. Our data also suggest that biological differences between interval and screen-detected cancers are more defined in older women. Future studies to confirm this finding and to elucidate novel markers for characterizing interval cancers may be more beneficial to this subgroup.