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Objective This study was designed to determine whether intensive lifestyle intervention (ILI) aimed at weight loss lowers cancer incidence and mortality. Methods Data from the Look AHEAD trial were examined to investigate whether participants randomized to ILI designed for weight loss would have reduced overall cancer incidence, obesity-related cancer incidence, and cancer mortality, as compared with the diabetes support and education (DSE) comparison group. This analysis included 4,859 participants without a cancer diagnosis at baseline except for nonmelanoma skin cancer. Results After a median follow-up of 11 years, 684 participants (332 in ILI and 352 in DSE) were diagnosed with cancer. The incidence rates of obesity-related cancers were 6.1 and 7.3 per 1,000 person-years in ILI and DSE, respectively, with a hazard ratio (HR) of 0.84 (95% CI: 0.68-1.04). There was no significant difference between the two groups in total cancer incidence (HR, 0.93; 95% CI: 0.80-1.08), incidence of nonobesity-related cancers (HR, 1.02; 95% CI: 0.83-1.27), or total cancer mortality (HR, 0.92; 95% CI: 0.68-1.25). Conclusions An ILI aimed at weight loss lowered incidence of obesity-related cancers by 16% in adults with overweight or obesity and type 2 diabetes. The study sample size likely lacked power to determine effect sizes of this magnitude and smaller.

Weight gain in adulthood is a risk factor for breast cancer; however, the impact on age of onset is unknown. The objective of this study was to investigate whether weight gain from early- to mid-adulthood influenced the timing of breast cancer onset. Increase in body mass index (BMI) from lowest adult BMI to BMI at diagnosis and age at which these events occurred were calculated from breast cancer survivors enrolled in a weight loss trial (n = 660). Quartiles (Q) of the average increase in BMI were determined and associations between weight gain and age at disease onset were analyzed using analysis of covariance and spline regression models. A significant linear trend was observed across the quartiles of BMI change for earlier age at diagnosis [Q1 52.3 (± 0.73), Q2 51.9 (± 0.70), Q3 49.6 (± 0.66), Q4 47.3 (± 0.67), p

Introduction Most smokers who try to quit do not use an evidence-based treatment (EBT), and in 2001, Hispanic/Latino quit-attempters were about half as likely as non-Hispanic white (NHW) quit-attempters to use one. This study analyzed the patterns of EBT use in Colorado across a recent decade, 2001−2012. Methods Data were from The Attitudes and Behaviors Survey, a random cross-sectional population-level telephone survey. Data included NHW and English-speaking Hispanic/Latino respondents from 2001 ( n =11,872), 2005 ( n =10,952), 2008 ( n =12,323), and 2012 ( n =13,265). Statistical analyses were conducted in 2014−2015. EBT measures included nicotine-replacement therapy, prescription cessation medication, telephone quit-line coaching, and other counseling. Bivariate and multiple logistic regression analyses evaluated associations across years between EBT use and ethnicity, adjusting for covariates. Results Any EBT use increased with each successive survey year, and the relative increase from 2001 to 2012 was greater among Hispanic/Latino than NHW quit-attempters (75.7% vs 38.7%). However, adjusted for covariates, Hispanic/Latino quit-attempters in 2012 were still 54% less likely to use any EBT (AOR=0.46, 95% CI=0.34, 0.63), 45% less likely to use nicotine-replacement therapy (AOR=0.55, 95% CI=0.39, 0.77), and 50% less likely to use a prescription cessation medication (AOR=0.50, 95% CI=0.30, 0.85). Ethnicity was unrelated to use of a quit-line or other counseling service. Conclusions EBT use for smoking cessation has increased over the past decade, with more rapid increase among English-speaking Hispanics/Latinos compared with NHWs, but a large use gap remains. Healthcare and public health efforts are needed to clarify and overcome factors contributing to this ongoing disparity.

Delivery of follow-up care to breast cancer survivors is an important public health issue due to their increasing number and the anticipated shortage of oncology providers. This study evaluated adherence to American Society of Clinical Oncology (ASCO)-recommended surveillance tests in a bi-ethnic cohort of long-term breast cancer survivors. Women (n = 298) in Arizona and Colorado who had previously participated in a population-based study of breast cancer were enrolled into a follow-up survey approximately 6 years post-diagnosis. ASCO-recommended surveillance (mammogram, clinical breast, and physical exam), other non-recommended tests (e.g. tumor markers, imaging scans), and patients’ beliefs were compared by provider type using multivariate logistic regression. No significant differences in patient self-report of physical exam or mammography prevalence by provider type was observed after adjustment for covariates. Receipt of surveillance tests not recommended by ASCO was higher among survivors who saw an oncologist (tumor marker tests: OR = 3.0, 95 % CI 1.5–5.8; and other blood tests: OR = 2.0, 95 % CI 1.1–3.5) as compared to those who routinely see a primary care physician. These observed differences persisted after adjustment for age, stage, lapse in insurance, education, or ethnicity. Although overutilization of non-recommended tests was observed among women who saw an oncologist, the majority of breast cancer survivors received ASCO-recommended surveillance regardless of provider type. Most breast cancer survivors receive recommended surveillance tests, whether their care is managed by a primary care physician or an oncologist, but some women receive unnecessary testing. Women should talk with their providers about tests recommended based on their past breast cancer diagnosis.

Physical activity is associated with reduced risk and progression of breast cancer, and exercise can improve physical function, quality of life, and fatigue in cancer survivors. Evidence on factors associated with cancer survivors’ adherence to physical activity guidelines from the American Cancer Society and the U.S. Department of Health and Human Services is mixed. This study seeks to help fill this gap in knowledge by examining correlates with physical activity among breast cancer survivors. Overweight or obese breast cancer survivors (N = 692) were examined at enrollment into a weight loss intervention study. Questionnaires and medical record review ascertained data on education, race, ethnicity, menopausal status, physical activity, and medical history. Measures of anthropometrics and fitness level were conducted. Regression analysis examined associations between physical activity and demographic, clinical, and lifestyle factors. Overall, 23 % of women met current guidelines. Multivariate analysis revealed that body mass index (p = 0.03), emergency room visits in the past year (p = 0.04), and number of comorbidities (p = 0.02) were associated with less physical activity. Geographic region also was associated with level of physical activity (p = 0.02), with women in Alabama reporting significantly less activity than those in other participating regions. The majority of overweight/obese breast cancer survivors did not meet physical activity recommendations. Physical activity levels were associated with degree of adiposity, geographic location, and number of comorbidities. The majority of overweight breast cancer survivors should be encouraged to increase their level of physical activity. Individualizing exercise prescriptions according to medical comorbidities may improve adherence.

Objective The purpose of this analysis was to examine the correlates of the physical and psychosocial domains of quality of life (QOL) in a cohort of breast cancer survivors participating in a weight loss intervention trial. Methods Correlates of QOL and psychosocial functioning were examined in 692 overweight or obese breast cancer survivors at entry into a weight loss trial. QOL was explored with three measures: Short-form 36 (SF-36), Impact of Cancer scale (IOC), and the Breast Cancer Prevention Trial (BCPT) symptom scales. Available data included information on weight and physical activity, as well as demographic and medical characteristics. Multivariate analyses were used to identify associations adjusted for other characteristics. Results In multivariate analysis, younger age was associated with higher negative impact scores (p

Carrying excess body fat is a leading cause of cancer. Epidemiologic evidence gives strong clues about the mechanisms that link excess adiposity to risk for several cancer sites. For postmenopausal breast cancer and endometrial cancer, the hyper-estrogenic state that is induced by excess body fatness is the likely cause. For esophageal cancer and gallbladder cancer, chronic local inflammation induced by acid reflux and gallstones is the likely cause, and for liver cancer, local inflammation induced by hepatic fatty infiltration is the likely cause. However, for several other cancers known to be associated with excess adiposity, including cancers of the colon, pancreas, ovary, kidney, and prostate, specific causes are not known. Possible candidates include elevated systemic or local tissue inflammation induced by adiposity and effects of the elevated levels of leptin, insulin, IGFs, and depressed immune function that are seen with excess adiposity. There is growing evidence that intentional weight loss not only reduces circulating levels of cancer-associated factors but that it also reduces cancer incidence and recurrence. Better research is needed to understand the mechanisms that link excess body fat to cancer risk as well as to understand the amount of weight loss needed for substantial cancer risk reduction. Finally, as we develop better understanding of the mediators of the effects of excess body fatness on cancer risk, we should identify pharmacologic interventions that target those mediators so that they can be used to complement weight loss in order to reduce cancer risk.

Background: Hispanic women have lower breast cancer incidence rates than non-Hispanic white (NHW) women. To what extent genetic versus nongenetic factors account for this difference is unknown. Methods: Using logistic regression, we evaluated the interactive influences of established risk factors and ethnicity (self-identified and identified by ancestral informative markers) on breast cancer risk among 2,326 Hispanic and 1,854 NHW postmenopausal women from the United States and Mexico in the Breast Cancer Health Disparities Study. Results: The inverse association between the percentage of Native American (NA) ancestry and breast cancer risk was only slightly attenuated after adjusting for known risk factors [lowest versus highest quartile: odds ratio (OR) =1.39, 95% confidence interval (CI) = 1.00–1.92 among U.S. Hispanics; OR = 1.92 (95% CI, 1.29–2.86) among Mexican women]. The prevalence of several risk factors, as well as the associations with certain factors and breast cancer risk, differed according to genetic admixture. For example, higher body mass index (BMI) was associated with reduced risk among women with lower NA ancestry only [BMI 30: OR = 0.65 (95% CI, 0.44–0.98) among U.S. Hispanics; OR = 0.53 (95% CI, 0.29–0.97) among Mexicans]. The average number of risk factors among cases was inversely related to the percentage of NA ancestry. Conclusions: The lower NA ancestry groups were more likely to have the established risk factors, with the exception of BMI. Although the majority of factors were associated with risk in the expected directions among all women, BMI had an inverse association among Hispanics with lower NA ancestry. Impact: These data suggest that the established risk factors are less relevant for breast cancer development among women with more NA ancestry. Cancer Epidemiol Biomarkers Prev; 26(5); 692–701. ©2016 AACR.

Breast cancer is the most common invasive cancer among women in developed countries. Obesity is a major risk factor for breast cancer recurrence and mortality in both pre-and postmenopausal women. Co-morbid medical conditions are common among breast cancer survivors. The Exercise and Nutrition to Enhance Recovery and Good Health for You (ENERGY) study is a 4-year randomized clinical trial of 693 overweight/obese women aged ≥21 years diagnosed with any early stage breast cancer (stages I[≥1 cm]-III) within the previous five years, designed to demonstrate the feasibility of achieving sustained weight loss and to examine the impact of weight loss on quality of life and co-morbidities, and to enable future exploration of biochemical mechanisms linking obesity to lower likelihood of disease-free survival. This trial is strategically designed as a vanguard for a fully-powered trial of women who will be evaluated for breast cancer recurrence and disease-free survival. Participants were recruited between 2010 and 2012 at four sites, had completed initial therapies, and had a body mass index between 25 and 45 kg/m2. The intervention featured a group-based cognitive-behavioral weight loss program with telephone counseling and tailored newsletters to support initial weight loss and subsequent maintenance, with the goal of 7% weight loss at two years. This study has high potential to have a major impact on clinical management and outcomes after a breast cancer diagnosis. This trial initiates the effort to establish weight loss support for overweight or obese breast cancer survivors as a new standard of clinical care.

PurposeComorbid 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 (12months) and 1-year postintervention (24months) 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.MethodsENERGY 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.ResultsAt 12months, women randomized to the intervention had fewer new medical conditions compared to the control group (19.6 vs. 32.2%, p&nbsp

We appreciate the interest that Hryniuk et al have expressed in our article that described the results of the Exercise and Nutrition to Enhance Recovery and Good Health for You (ENERGY) trial, a behavioral weight-loss intervention in overweight or obese breast cancer survivors. As we noted in our article, we concur that women who have been diagnosed and treated for breast cancer often have special issues, such as treatment-related musculoskeletal problems, enduring psychosocial symptoms (especially fatigue and depression), and changes in body composition associated with cancer treatment, which can complicate weight management efforts. Moreover, breast cancer survivors also may have more foodrelated concerns and body image issues that must be addressed to promote adherence to weight loss efforts. The ENERGY intervention was tailored to breast cancer survivors and, hence, addressed their preferences and the challenges specific to breast cancer-related symptoms, including fatigue, symptoms of estrogen withdrawal, body image concerns, and lymphedema. Details about the screening process and specific medical and psychiatric exclusion criteria for the ENERGYtrial have been previously published. Similar to Hryniuk et al, we excluded women who were bipolar or schizophrenic, but we also screened out individuals with other psychoses, bulimia nervosa, and anorexia nervosa, as well as serious personality disorders and serious depression. Several psychosocial measures were conducted at baseline and regular intervals, including risk for depression, using the Center for Epidemiologic Studies Depression Scale (CES-D). In addition, we queried whether participants were currently being treated for depression. As we have previously reported, 137 of the 692 participants (approximately 20%) were considered at risk for depression (CES-D score $16) at study entry, and 21% reported that they were currently being treated for depression. These two measures were strongly associated (P , .001). In response to the suggestion of Hryniuk et al that depression might be an important determinant of weight loss, we conducted an exploratory analysis of the relationship between depression and subsequent study outcomes in the ENERGY trial. There were no differences in weight loss, drop-out rate, or attendance at group or individual intervention sessions at any follow-up time point by depression status based on the CES-D score or diagnosis and treatment of depression. Thus, our data from a relatively large population of overweight and obese breast cancer survivors are not in agreement with those reported by Hryniuk et al. However, it must be noted that our population could have differed because we screened out individuals with severe depression and other disorders that may have been included in the Hryniuk et al sample. Nonetheless, based on our extensive experience with diet and weight-loss interventions in this population, we believe any weight control interventions in cancer survivors need to also address enduring psychosocial symptoms such as cancer-related fatigue and depression.

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, approximately 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 o r 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.

BACKGROUND: Multiple sclerosis (MS) is a chronic, neurodegenerative inflammatory disease that affects approximately 400,000 Americans, the majority of whom are female. Although MS prevalence is higher among females, males are more likely to have a more progressive clinical course. For both genders, use of disease-modifying medications (DMMs) in the clinical management of MS is pivotal in altering the natural course and diminishing progressive disability over time. OBJECTIVES: To evaluate gender differences in self-reported symptom awareness and perceived ability to manage therapy among MS patients taking a DMM. METHODS: During February 2008, a self-administered, 42-item survey was mailed to 4,700 commercially insured patients taking a DMM to treat MS. Survey items measured self-reported clinical characteristics, symptom awareness, and perceived ability to manage therapy. Bivariate analyses assessed associations of gender with other predictor and outcome variables, including demographic characteristics, clinical disease characteristics, specific DMM used at the time of the survey, self-reported symptom awareness, and perceived ability to manage therapy. Logistic regression analyses further assessed the associations of gender with symptom awareness and perceived ability to manage MS after adjustment for relevant covariates (age at diagnosis, educational level, income, current DMM, type of pharmacy where drug was dispensed, frequency of flare-ups, and clinical course of disease). RESULTS: The response rate was 44.1% (n = 2,074). Of the 2,022 respondents with useable surveys, 80.6% were female; 82.3% had relapsingremitting MS; and 83.1% were taking one of the most commonly used DMMs (intramuscular interferon beta-1a 33.4%, subcutaneous interferon beta-1a 15.9%, and glatiramer acetate 33.8%). Compared with female patients, males were older and a greater proportion had a more progressive clinical course of disease. In multivariate models, female patients were more likely than males to report recognition of a relapse/exacerbation (odds ratio [OR] = 1.37, 95% CI = 1.03-1.82) and to report knowing what to do when experiencing a relapse/exacerbation (OR = 1.34, 95% CI = 1.011.77) or if they missed a dose of medication (OR = 1.78, 95% CI = 1.08-2.43). Females were also more likely to report awareness of treatment options (OR = 1.48, 95% CI = 1.07-2.07) and to think that DMMs were helping their MS (OR = 1.32, 95% CI = 1.02-1.77). CONCLUSIONS: Female MS patients report better awareness of disease symptoms and have more positive perceptions of their ability to manage therapy with DMMs than male MS patients. These findings suggest that male MS patients may require additional education and support to manage their disease and therapy needs. Knowledge of these gender differences potentially could help managed care organizations to improve therapy adherence by guiding gender-specific patient support programs.

Insulin resistance is thought to mediate the association between obesity and colorectal neoplasia, but no prior studies have assessed stimulated insulin sensitivity as a risk factor for colorectal neoplasia. This prospective study examined the association between insulin sensitivity measured directly using the frequently sampled intravenous glucose tolerance test (FSIGT) and later risk of colorectal adenomas. Among participants with a range of glucose tolerance levels enrolled in the Insulin Resistance Atherosclerosis Study, colonoscopies were conducted on 600 participants ages ≥50 yr, regardless of symptoms, about 10 yr after the first FSIGT and 5 yr after the second. Multiple logistic regression analyses were used. Within this cohort, diabetes was not associated with colorectal adenoma risk [∼10 yr prior to colonoscopy adjusted odds ratio (OR(adj)) 1.00; 95% confidence interval (CI), 0.62-1.62 or ∼5 yr prior to colonoscopy OR(adj) 0.96; 95% CI, 0.62-1.50]. Among non-diabetic participants, insulin sensitivity was not associated with colorectal adenoma risk at either prior study visit [lowest vs. highest insulin sensitivity, ∼10 yr prior to colonoscopy OR(adj) 0.93; 95% CI 0.50-1.71 and ∼5 yr prior to colonscopy OR(adj) 0.74; 95% CI, 0.38-1.46]. These results suggest that factors other than insulin sensitivity mediate the relationship between obesity and colorectal neoplasia.

In 1998, the American Cancer Society (ACS) set a challenge goal for the nation to reduce cancer incidence by 25% over the period between 1992 and 2015. This report examines the trends in cancer incidence between 1992 and 2004. Trends were calculated using data on incident malignant cancer cases from the Surveillance, Epidemiology, and End Results (SEER) Registry. Delay-adjusted incidence trends for all cancer sites; all cancer sites without prostate cancer included; all cancer sites stratified by gender, age, and race; and for 20 selected cancer sites are presented. Over the first half of the ACS challenge period, overall cancer incidence rates have declined by about 0.6% per year. The greatest overall declines were observed among men and among those aged 65 years and older. The pace of incidence reduction over the first half of the ACS challenge period was only half that necessary to put us on target to achieve the 25% cancer incidence reduction goal in 2015. New understandings of preventable factors are needed, and new efforts are also needed to better act on our current knowledge about how we can prevent cancer, especially by continuing to reduce tobacco use and beginning to reverse the epidemic of obesity.

Adiposity has been recognized as a risk factor for colorectal adenoma, but the influence of weight gain, adipose tissue distribution, and possible differences between ethnic/racial and gender groups remains unanswered. The aim of this prospective study was to examine the association between adiposity and weight change and colorectal adenoma risk. Over ∼10-year period, anthropometric measures and other risk factors were measured at three time points in the multicenter multiethnic Insulin Resistance Atherosclerosis Study cohort. Colonoscopies were then conducted on 600 cohort participants regardless of symptoms whose mean age at colonoscopy was 64 years. Multivariate logistic regression analyses were used to assess the association between colorectal adenomas and measures of adiposity and weight change over the ∼10-year period before colonoscopy. Obesity was positively associated with risk of colorectal adenomas at the time of colonoscopy [adjusted odds ratio (ORadj), 2.16; 95% confidence interval (95% CI), 1.13-4.14] and was stronger in women (ORadj, 4.42; 95% CI, 1.53-12.78) than in men (ORadj, 1.26; 95% CI, 0.52-3.07). The risk of adenomas increased among participants who gained weight compared with those who maintained weight over the ∼5 years (ORadj, 2.30; 95% CI, 1.25-4.22) and ∼10 years (ORadj, 2.12; 95% CI, 1.25-3.62). These associations were similar for both advanced and nonadvanced adenomas. These results suggest a positive association between obesity, weight gain, and colorectal adenoma risk. Stronger associations were observed when obesity was measured at the time of colonoscopy, suggesting that obesity may be a promoting factor in the growth of colorectal adenomas. (Cancer Epidemiol Biomarkers Prev 2007;16(3):526–31)

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&nbsp

Purpose Obesity increases risk for all-cause and breast cancer mortality and comorbidities in women who have been diagnosed and treated for breast cancer. The Exercise and Nutrition to Enhance Recovery and Good Health for You (ENERGY) study is the largest weight loss intervention trial among survivors of breast cancer to date. Methods In this multicenter trial, 692 overweight/obese women who were, on average, 2 years since primary treatment for early-stage breast cancer were randomly assigned to either a group-based behavioral intervention, supplemented with telephone counseling and tailored newsletters, to support weight loss or a less intensive control intervention and observed for 2 years. Weight and blood pressure were measured at 6, 12, 18, and 24 months. Longitudinal mixed models were used to analyze change over time. Results At 12 months, mean weight loss was 6.0% of initial weight in the intervention group and 1.5% in the control group (P < .001). At 24 months, mean weight loss in the intervention and control groups was 3.7% and 1.3%, respectively (P < .001). Favorable effects of the intervention on physical activity and blood pressure were observed. The weight loss intervention was more effective among women older than 55 years than among younger women. Conclusion A behavioral weight loss intervention can lead to clinically meaningful weight loss in overweight/obese survivors of breast cancer. These findings support the need to conduct additional studies to test methods that support sustained weight loss and to examine the potential benefit of intentional weight loss on breast cancer recurrence and survival.

Objectives Human papillomavirus (HPV) infections are the cause of most, if not all, cervical cancers. Women consistently positive for oncogenic type HPV infections have a greater risk of developing cervical dysplasia compared with women transiently infected. HPV infection alone appears to be insufficient to produce disease, suggesting that other cofactors may be needed. Folate, vitamin B12, and homocysteine, through their role in DNA methylation, may be involved in cervical neoplasia. Methods This study examined the associations between HPV persistence and circulating folate, vitamin B12, and homocysteine levels among 91 low-income Hispanic women. Further, the relation of these nutrients to cervical pathology was evaluated. HPV status was determined at two visits approximately 3 mo apart. Results Adjusted mean circulating concentrations of folate, vitamin B12, and homocysteine were not statistically different between women with two positive HPV tests, one positive test, or two negative HPV tests. No association was observed between tertiles of folate, vitamin B12, or homocysteine and HPV persistence risk. Further, adjusted mean levels of these nutrients were not statistically different between cytologic grades. Conclusions Results from this small study did not support a role for folate, vitamin B12, or homocysteine in HPV persistence or cervical dysplasia.

Objective: Data have suggested that higher levels of nutrients are protective against HPV persistence and cervical neoplasia. This study assessed the role of circulating nutrients on clearance of oncogenic HPV infections. Methods: Women were followed prospectively with visits at baseline and approximately 4- and 10-months post-baseline. At each visit, 15 oncogenic HPV types were determined. Plasma levels were assessed at the 4-month visit for retinol, carotenoids (i.e., α-, trans-β-, cis-β-carotene, α-, β-cryptoxanthin, lutein, zeaxanthin, trans- and cis-lycopene), tocopherols (i.e., α-, δ-, and γ-tocopherol), folate and vitamin B12. Using multivariate Cox proportional hazards models, time to clearance analyses of oncogenic HPV infections were conducted for 84 women with at least one oncogenic infection at baseline. Hazard ratios (HR) were estimated for the association of HPV clearance to each nutrient tertile and to determine linear trends. Results: The likelihood of clearing an oncogenic HPV infection was significantly higher with increasing levels of trans-lycopene (p for trend, 0.025) and cis-lycopene (p for trend, 0.010). The adjusted hazard ratios of the highest tertiles of trans- and cis-lycopene were 2.79 (95% CI = 1.17–6.66) and 2.92 (95% CI = 1.28–6.63) compared with the lowest tertiles. Conclusions: Higher concentrations of trans- and cis-lycopene may reduce the time to clearance of an oncogenic HPV infection.

Objective: The purpose of this investigation was to assess the association between smoking and clearance of oncogenic human papillomavirus (HPV) infection. Methods: A prospective cohort study of 346 women aged 18–35 years was conducted. HPV testing was conducted with the Hybrid Capture II (HC II) system and polymerase chain reaction (PCR) with genotyping using the reverse line blot method. At each visit tobacco exposure, reproductive, and sexual histories were assessed. Probability of clearing an oncogenic HPV infection and duration of oncogenic HPV infections by smoking status was assessed. Results: Regardless of method used, HC II or PCR, ever smokers maintained an HPV infection significantly longer (median duration of 8.5 months vs 10.7 months, never vs ever smokers), and had a lower probability of clearing an oncogenic infection compared with women who never smoked. Smoking duration was significantly associated with HPV clearance, and a dose response was observed. Older age (> 13 years) at smoking initiation was significantly associated with a reduced probability of clearing an oncogenic HPV infection. Conclusion: This is the first study to demonstrate that smoking promotes early cervical carcinogenic events by increasing duration of oncogenic HPV infections and decreasing probability of clearing oncogenic infections.

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-1β, 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-1β (MIP-1β) 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-1β) 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.

Purpose: Changes in cancer therapy, in addition to changes in obesity prevalence, suggest the need for a current assessment of weight gain patterns following breast cancer diagnosis. The aim of this study was to evaluate factors associated with weight gain among breast cancer survivors prior to enrolling into a behavioral weight loss intervention. Methods: Anthropometric measures and data on weight-related factors were collected at baseline on 665 breast cancer survivors. Postdiagnosis weight gain was determined between entry into the trial and previous diagnosis up to 5 years. Multivariate logistic regression analyses were used to evaluate the association between weight gain and influencing factors. Results: The mean weight gain was 4.5 % body weight (standard deviation = 10.6); 44 % of women experienced ≥5 % body weight gain. The risk of weight gain was inversely associated with age (adjusted odds ratio (ORadj) = 0.97, 95 % confidence interval (95 % CI) 0.95-0.99), Hispanic ethnicity (ORadj = 0.30, 95 % CI 0.13-0.68), and overweight (ORadj = 0.11, 95 % CI 0.05-0.23) or obese (ORadj = 0.03, 95 % CI 0.02-0.07) status at diagnosis and positively associated with time elapsed since diagnosis (ORadj = 1.19/year, 95 % CI 1.04-1.36). Women prescribed aromatase inhibitors were 46 % less likely to gain weight compared to women prescribed selective estrogen-receptor modulators (ORadj = 0.54, 95 % CI 0.31-0.93). The risk of weight gain was positively associated with smoking at diagnosis (ORadj = 2.69, 95 % CI 1.12-6.49) although this was attributable to women who subsequently quit smoking. Conclusions: Postdiagnosis weight gain is common and complex and influenced by age, ethnicity, weight, smoking status, time elapsed since diagnosis, and endocrine-modulating therapy. Implications for cancer survivors: Weight gain continues to be a concern following a diagnosis of breast cancer. Factors influencing this weight gain include age, ethnicity, weight, smoking status, time elapsed since diagnosis, and endocrine-modulating therapy. Effective weight management strategies are needed for this population of women. © 2014 Springer Science+Business Media New York.

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.

Persistent infection with human papillomavirus (HPV) is the primary etiologic factor for cervical cancer. The synergistic effect of carotenoids on HPV persistence has not been examined. To explore these potential synergies, we developed 2 measures of carotenoid status using circulating and dietary intake nutrients in which each nutrient was given equal weighting. We then compared persistent HPV infection with its counterpart, intermittent infection. In the analysis using the Crude Index, no association was observed between circulating nutrients and persistent infection with oncogenic HPV [odds ratio (OR)(adjusted) = 0.8, 95% confidence interval (CI) = 0.3-2.2)] or any type HPV (OR(adjusted) = 0.8, 95% CI = 0.3-2.1). Similar results were obtained using the Cumulative Index. However, associations between dietary intake and persistent infection were observed using both indexes. When the analysis was restricted to oncogenic HPV, a 50% higher risk was observed for women with low dietary carotenoid status using the Crude Index (OR(adjusted) = 1.5, 95% CI = 0.6-3.7). In the analysis using any type HPV, the adjusted OR for women with low dietary intake of combined carotenoids using the Cumulative Index was 2.4 (95% CI = 1.1-5.2). These results may be consistent with the hypothesis that low levels of carotenoids may increase the risk of persistent HPV infection.

The purpose of this study is to investigate 1-year adherence rates to aromatase inhibitors (AI) and to determine risk factors for non-adherence among commercially insured post-menopausal breast cancer patients. A retrospective cohort of 13,593 commercially insured breast cancer patients with a prescription claim for an AI therapy (exemestane, anastrozole, and letrozole) in 2006 were identified using the MarketScan® Commercial Claims and Encounters Database. Adherence was calculated by the medication possession ratio (MPR) for a 1-year period following the initial claim in 2006. The main outcome variable was non-adherence (

In 2008, approximately 8 percent (∼5.5 million) of individuals with commercial insurance were enrolled in consumer-directed health plans (CDHPs) (Claxton et al. 2008). These “high-deductible” health insurance plans encourage contributions by the employer and/or employee into tax-favorable accounts. These accounts are then used for health care–related expenses and, unlike medical savings accounts, unused funds in 1 year can be rolled over for future health care expenditures. Once the account is exhausted, the employee must pay any health expenditures out of pocket until an annual deductible is met. Upon satisfying the annual deductible, standard health coverage with copays and/or coinsurance becomes available. The CDHP insurance model relies on member involvement in health care utilization/cost decisions to manage health care expenditures (Buntin et al. 2006). Concerns have been raised that CDHPs may discourage patients from obtaining essential medical care and/or chronic medications in order to avoid out-of-pocket expenditures (Buntin et al. 2006; Ross 2006; Wilensky 2006; Hibbard, Greene, and Tusler 2008;). The evidence to date has been mixed. Parente, Feldman, and Christianson (2004) compared pharmacy and medical claims between enrollees in a CDHP (the majority with individual and family deductibles of U.S.$1,500 and U.S.$3,000, respectively), health maintenance organization (HMO), and preferred provider organization (PPO) health plans. One year after introduction of the CDHP, enrollees in the CDHP had higher adjusted mean rates of prescriptions filled and physician office visits compared with PPO but lower rates compared with HMO enrollees. On the other hand, a retrospective analysis of medical and pharmacy claims data reported a reduction in total medical office visits in the first year for enrollees of a “high-deductible” CDHP (annual individual deductible U.S.$1,500) compared with enrollees of a PPO health plan (Hibbard, Greene, and Tusler 2008). This decline occurred indiscriminately for both low- and high-priority medical office visits. Conversely, emergency department visits declined after enrollment into a high-deductible health plan (annual deductibles ranging from U.S.$500 to U.S.$2,000 for individual and U.S.$1,000 to U.S.$4,000 for families) as compared with enrollees of traditional HMO plans (Wharam et al. 2007). While there was no difference in the initial emergency visit, reduction in subsequent low-severity emergency visits occurred after enrollment into a high-deductible health plan. A retrospective analysis of employees and their dependents enrolled in a high-deductible CDHP (annual family deductible U.S.$3,000 with an employer-funded account of U.S.$1,500) reported that compared with enrollees with a PPO health plan, the CDHP enrollees were more likely to discontinue antihypertensive and lipid-lowering pharmacotherapy after implementation of the CDHP (Greene et al. 2008a). Furthermore, no difference in adherence was observed by plan type among employees who continued with their chronic medication therapy or no change in generic utilization, suggesting that additional resources are needed to encourage CDHP enrollees to make beneficial health care decisions. Navigating the CDHP insurance model for the patient involves multifaceted health care decision making while weighing personal expenditures (Goodman 2004; Greene et al. 2008b;). In lieu of the complexity of this decision making, educational programs may assist CDHP enrollees in becoming more informed health care consumers and decision makers. While patient education programs have been demonstrated to influence medication use (Cormack et al. 1994; Grace et al. 2002; Delate and Henderson 2005; Meissner et al. 2006; Tran and Billups 2008;), no information is available on the effect of enrollee education programs in CDHPs. The purpose of this study was to assess the impact of a multifaceted educational intervention on medication decision making by comparing the rates of chronic medication persistence and lower-cost medication substitution between CDHP enrollees without an educational outreach and CDHP enrollees with the medication educational outreach in a single national employer.

Public health actions in response to new threats are often taken despite uncertainty about the efficacy of the action. The challenge, then, is to make ongoing judgments about whether actions are taken too soon, before a sufficient understanding of the efficacy of interventions is known, or too late, after much of the prevention potential is lost. The ongoing obesity epidemic presents exactly this type of challenge. General lessons learned from the AIDS and tobacco epidemics as well as others can be useful now as we contemplate options for reversing the ongoing epidemic of obesity in the United States. In this article we briefly review current evidence regarding the efficacy of obesity interventions in both clinical and community settings. We conclude that although little direct evidence is available on the efficacy of interventions for the obesity epidemic, there are some reasonable options derived from experience with other public health epidemics that can contribute to the solution of the obesity problem.

Because the link between adiposity (overweight and obesity) and breast cancer outcomes has been apparent for many years, it seems that a randomized controlled trial to test the effects of weight loss on breast cancer recurrence is long overdue. In this commentary we will review the rationale for such a trial and comment on how emerging changes in clinical practice and surprising observations from recent research would suggest that if we had already begun such a trial we might well have designed it incor? rectly. Perhaps, then, it is fortunate that such a large-scale trial has not yet been initiated. Our bottom line: whether such a trial should now be done among pre-menopausal breast cancer survivors, among post-menopausal survivors, among both, or perhaps among neither, is not clear. After menopause, adiposity is clearly associated with increased risk of incident breast cancer [1-4]. Adiposity has also been found to be associated with a higher risk of breast cancer recurrence and/or poorer survival among post-menopausal women, though the evidence for this is mixed [1, 5-8]. The confounding effects of tobacco smoking and treatment on the adiposity-outcome rela? tionships may account for variation across studies. After menopause, when estrogen levels predict risk of incident breast cancer, the principal pathway for estrogen produc? tion is via the enzyme aromatase, which converts andro gens to estrogens, mainly in adipose tissues [9-11]. The etiologic role of estrogen in post-menopausal breast cancer has been proven by large trials demonstrating that estrogen replacement therapy increases breast cancer incidence [12], and that estrogen receptor blockade lowers risk of both breast cancer incidence [13] and recurrence [14]. That adiposity affects breast cancer risk via an estrogen pathway is supported by the observations that adiposity is a signif? icant predictor of breast cancer risk only among post menopausal women who do not take hormone replacement supplements [IS], and when estrogen receptors are blocked with Tamoxifen, the adverse effect of adiposity on breast cancer recurrence is reduced [16]. Physical activity, a necessary element in long-term weight control, may also affect breast cancer recurrence via an estrogen pathway as physical activity is protective against breast cancer recur? rence among women who have had cancers positive for estrogen receptors but not among women with cancers negative for estrogen receptors [17]. A combination of both weight loss and increased physical activity reduce estrogen levels [18]. Whether weight loss could therefore reverse the adverse effects of adiposity on breast cancer is not certain. There is some observational evidence that is consistent with the idea that weight loss can reduce breast cancer risk [15, 19, 20]. Observational studies assessing the effects of weight loss on recurrence will always be difficult to interpret, though, due to a myriad of confounding factors associated with intentional weight loss and due to the effects of both breast cancer and its treatment on body weight [21]. In many ways, then, the rationale for a trial of weight loss to benefit breast cancer survival has seemed most compelling for post-menopausal women, in whom adi? posity increases risk of breast cancer incidence, is associ? ated with poorer disease-free survival, and causes increased levels of estrogens which are proven to directly affect breast cancer risk. However, the new standard of care for estrogen receptor positive breast cancer may soon elimi? nate the pathway whereby a weight loss trial could be T. Byers (E) ? R. L. Sedjo Department of Preventive Medicine and Biometrics, University of Colorado School of Medicine, 4200 East Ninth Avenue, Box B-119, Denver, CO 80262, USA e-mail: Tim.Byers@uchsc.edu

The natural history of type-specific human papillomavirus (HPV) infections was examined in a cohort of 331 women aged 18-35 years who self-referred for routine gynecological care. Participants underwent a gynecological examination at baseline and at approximately 4 and approximately 10 months after baseline. Cervical samples were collected for HPV testing and genotyping at each visit, as was information on reproductive, sexual, and medical histories. The rate of new HPV infections was 2.9% per month; the highest rates were observed for HPV types 16, 39, 84, and 51. Among women who tested negative for HPV at baseline, the cumulative probability of acquiring an oncogenic HPV strain during a 12-month follow-up period was 0.32, compared with 0.18 for nononcogenic strains. Women who had had >/=1 new male sex partner in the recent past were significantly more likely to acquire a new HPV infection (relative hazard, 2.39; 95% confidence interval, 1.20-4.76). The median time to clearance of infection was significantly longer for oncogenic strains (9.8 months) than for nononcogenic strains (4.3 months).

Background: High levels of circulating insulin-like growth factor-1 (IGF-1) have been associated with increased risks of several cancers, including colorectal cancer. Methods: In a sub-cohort of the Insulin Resistance and Atherosclerosis Study (IRAS), we examined the associations between circulating IGF-1 and IGF-1/IGFBP-3 molar ratios, as well as their change patterns during 10-year follow-up, with the presence of colorectal adenomatous polyps at the end of the follow-up. Results: The general trend was decrease of both variables with age. Based on this trend, two patterns were considered: “no increase” (variation within 15% of baseline and/or decrease) and “ever increase” (at least one increase of > 15%). In the subgroup of participants with normal glucose tolerance, “ever increase” was positively associated with colorectal adenoma: ORs were 3.65 (1.30-10.8) and 2.83 (1.00-8.22) for IGF-1 and IGF-1/IGFBP-3, respectively. No association was found between actual levels of IGF-1 or IGF-1/IGFBP-3 at any time point and the presence of colorectal adenoma. Conclusion: Our data suggest that increase in circulating IGF-1 and IGF-1/IGFBP-3 may represent an unnatural trend of a disturbed signaling pathway, which could favor the development of precancerous lesions, such as colorectal adenoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4637. doi:10.1158/1538-7445.AM2011-4637