Surgery

Background: Obesity and hypertension and their associated health complications disproportionately affect communities of color and people of lower socioeconomic status. Recruitment and retention of these populations in research trials, and retention in weight loss trials has been an ongoing challenge.

research has explored the potential benefits of lifestyle choices among cancer survivors. In 2012, ACS published an update (2), and other organizations have now developed guidelines for cancer survivors (3). The unifying message is that lifestyle has a major influence for cancer survivors, just as it is essential for cancer prevention (4). The key dietary recommendations across these reports are: 1) choose fruits and vegetables; 2) choose whole grains over refined grains; 3) choose fish and poultry over red and processed meats; 4) choose unsaturated fats, such as olive oil, over saturated and trans-fats; and 5) choose low-fat over full-fat dairy. In addition, recommendations call for the maintenance of a healthy body weight, regular physical activity, and cessation of smoking and avoidance of tobacco. Together, these behaviors address the increased risk for other diseases that many cancer survivors also experience.

BACKGROUND: Primary care clinicians can play an important role in identifying individuals at increased risk of cancer, but often do not obtain detailed information on family history or lifestyle factors from their patients. OBJECTIVE: We evaluated the feasibility and effectiveness of using a web-based risk appraisal tool in the primary care setting. DESIGN: Five primary care practices within an academic care network were assigned to the intervention or control group. PARTICIPANTS: We included 15,495 patients who had a new patient visit or annual exam during an 8-month period in 2010-2011. INTERVENTION: Intervention patients were asked to complete a web-based risk appraisal tool on a laptop computer immediately before their visit. Information on family history of cancer was sent to their electronic health record (EHR) for clinicians to view; if accepted, it populated coded fields and could trigger clinician reminders about colon and breast cancer screening. MAIN MEASURES: The main outcome measure was new documentation of a positive family history of cancer in coded EHR fields. Secondary outcomes included clinician reminders about screening and discussion of family history, lifestyle factors, and screening. KEY RESULTS: Among eligible intervention patients, 2.0 % had new information on family history of cancer entered in the EHR within 30 days after the visit, compared to 0.6 % of eligible control patients (adjusted odds ratio = 4.3, p = 0.03). There were no significant differences in the percent of patients who received moderate or high risk reminders for colon or breast cancer screening. CONCLUSIONS: Use of this tool was associated with increased documentation of family history of cancer in the EHR, although the percentage of patients with new family history information was low in both groups. Further research is needed to determine how risk appraisal tools can be integrated with workflow and how they affect screening and health behaviors.

Physical inactivity and high mammographic breast density have both been associated with increased breast cancer risk. However, the association between physical activity and mammographic breast density remains inconsistent. In the European Prospective Investigation of Cancer (EPIC)-Norfolk population-based cohort study (United Kingdom), the authors investigated the cross-sectional association between physical activity level at baseline during 1993-1997 and breast density among 1,394 postmenopausal, cancer-free women. Usual physical activity was assessed by a brief, validated questionnaire. Percentage breast density was determined visually from mammograms by three trained radiologists using the Boyd six-category scale. The association between physical activity level and breast density risk category was examined. No statistically significant association between physical activity and percentage breast density was observed in the unadjusted or adjusted regression models. A suggested increase in breast density for the most active women in the unadjusted regression analysis (odds ratio ¼ 1.13, 95% confidence interval: 0.71, 1.80) was reversed after inclusion of body mass index and reproductive and lifestyle variables (odds ratio ¼ 0.78, 95% confidence interval: 0.45, 1.34). The lack of an association between physical activity and percentage breast density suggests that an association between physical activity and breast cancer risk is unlikely to be mediated through an effect on mammographic breast density. breast; breast neoplasms; exercise; mammography; motor activity Abbreviations: BMI, body mass index; EPIC, European Prospective Investigation of Cancer.

Molecular mechanisms mediating the progression of ductal carcinoma in situ (DCIS) to invasive breast cancer remain largely unknown. We used gene expression profiling of human DCIS (n ¼ 53) and invasive breast cancer (n ¼ 51) to discover uniquely expressed genes that may also regulate progression. There were 470 total differentially expressed genes (!2-fold; P < 0.05). Elevated expression of genes involved in synthesis and organization of extracellular matrix was particularly prominent in the epithelium of invasive breast cancer. The degree of overlap of the genes with nine similar studies in the literature was determined to help prioritize their potential importance, resulting in 74 showing overlap in !2 studies (average 3.6 studies/gene; range 2-8 studies). Using hierarchical clustering, the 74-gene profile correctly categorized 96% of samples in this study and 94% of samples from 3 similar independent studies. To study the progression of DCIS to invasive breast cancer in vivo, we introduced human DCIS cell lines engineered to express specific genes into a "mammary intraductal DCIS" xenograft model. Progression of xenografts to invasive breast cancer was dramatically increased by suppressing four genes that were usually elevated in clinical samples of DCIS, including a protease inhibitor (CSTA) and genes involved in cell adhesion and signaling (FAT1, DST, and TMEM45A), strongly suggesting that they normally function to suppress progression. In summary, we have identified unique gene expression profiles of human DCIS and invasive breast cancer, which include novel genes regulating tumor progression. Targeting some of these genes may improve the detection, diagnosis, and therapy of DCIS. Cancer Res; 72(17); 4574-86. Ó2012 AACR.

Vitamin D and calcium have been shown to have protective effects against breast cancer development in animal studies. Vitamin D and calcium play important anticarcinogenic roles in animal studies. Exposures between menarche and first birth may be important in breast development and future breast cancer risk. However, the relations between adolescent vitamin D and calcium intake and the risk of proliferative benign breast disease (BBD), a marker of increased breast cancer risk, have not yet been evaluated. We examined these associations in the Nurses' Health Study II. Among the 29,480 women who completed an adolescent diet questionnaire in 1998, 682 proliferative BBD cases were identified and confirmed by centralized pathology review between 1991 and 2001. Hazard ratios (HRs) and 95 % confidence intervals (CIs) were estimated by Cox proportional hazards regression and adjusted for potential confounders. A suggestive inverse association was observed between adolescent total vitamin D intake and proliferative BBD. Women in the highest quintile of vitamin D intake during adolescence had a 21 % lower risk (multivariate HR (95 % CI): 0.79 (0.61, 1.01), ptrend = 0.07) of proliferative BBD than women in the lowest quintile. Results were essentially the same when the analysis was restricted to prospective cases (n = 142) diagnosed after return of the adolescent diet questionnaire and independent of adult vitamin D intake. Adolescent total milk intake was positively associated with proliferative BBD (C3 servings/day vs. \1 serving/day HR (95 % CI): 1.41 (0.91, 2.17), p-trend = 0.03), after additional adjustment for total vitamin D. Calcium intake during adolescence was not associated with proliferative BBD (ptrend = 0.91). Vitamin D intake during adolescence may be important in the earlier stage of breast carcinogenesis. These findings, if corroborated, may suggest new pathways and strategies for breast cancer prevention. Keywords Adolescent diet Á Vitamin D Á Calcium Á Proliferative BBD Abbreviations AH Atypical hyperplasia BBD Benign breast disease CI Confidence interval FFQ Food-frequency questionnaire HR Hazard ratio HS-FFQ High school food-frequency questionnaire ICC Intraclass correlation coefficients NHS Nurses' Health Study NHSII Nurses' Health Study II OC Oral contraceptive

We conducted a systematic review investigating body fat distribution in older adults and its association with morbidity and mortality. Our search yielded 2,702 citations. Following three levels of screening, 25 studies were selected to evaluate the association between body fat distribution and comorbidity, and 17 studies were used in the mortality analysis. Most of the selected studies in our analyses used anthropometric measures, e.g., body mass index (BMI), waist circumference, and waist-hip ratio; relatively few studies used direct measures, such as body fat/lean mass, and percentage body fat. Studies reported inconsistent findings regarding the strongest predictor(s) of morbidity and mortality. However, the majority of studies suggested that BMI per se was not the most appropriate predictor of morbidity and mortality in the elderly because of its inability to discern or detect age-related body fat redistribution. In addition, studies using BMI found that the optimal BMI range for the lowest mortality in the elderly was overweight (25 kg/m 2 ≤ BMI < 30 kg/m 2 ) or mildly obese (30 kg/m 2 ≤ BMI < 35 kg/m 2 ). Our findings suggest that the current clinical guidelines, recommending that overweight and obesity are major risk factors for increased morbidity and mortality are not applicable to this population. Therefore, the central message of this review is to admonish the government to establish new guidelines specifically for this population, using a combination of body fat distribution measurements, and to certify that these guidelines will not be applied to inappropriate populations.

More than half of the cancer occurring today is preventable by applying knowledge that we already have. Tobacco, obesity, and physical inactivity are the modifiable causes of cancer that generate the most disease. Cancer burden can be reduced by alterations in individual and population behaviors and by public health efforts as long as these changes are driven by sound scientific knowledge and social commitment to change. The obstacles to these efforts are societal and arise from the organization of institutions, including academia, and in the habits of daily life. To achieve maximal possible cancer prevention, we will need better ways to implement what we know and improved infrastructure that will better incentivize and support transdisciplinary, multilevel research and successful intervention.

Percent mammographic breast density (PMD) is a strong heritable risk factor for breast cancer. However, the pathways through which this risk is mediated are still unclear. To explore whether PMD and breast cancer have a shared genetic basis, we identified genetic variants most strongly associated with PMD in a published meta-analysis of five genome-wide association studies (GWAS) and used these to construct risk scores for 3628 breast cancer cases and 5190 controls from the UK2 GWAS of breast cancer. The signed per-allele effect estimates of SNPs were multiplied with the respective allele counts in the individual and summed over all SNPs to derive the risk score for an individual. These scores were included as the exposure variable in a logistic regression model with breast cancer case-control status as the outcome. This analysis was repeated using ten different cut-offs for the most significant density SNPs (1-10% representing 5,222-50,899 SNPs). Permutation analysis was also performed across all 10 cut-offs. The association between risk score and breast cancer was significant for all cut-offs from 3-10% of top density SNPs, being most significant for the 6% (2-sided P=0.002) to 10% (P=0.001) cut-offs (overall permutation P=0.003). Women in the top 10% of the risk score distribution had a 31% increased risk of breast cancer [OR= 1.31 (95%CI 1.08-1.59)] compared to women in the bottom 10%. Together, our results demonstrate that PMD and breast cancer have a shared genetic basis that is mediated through a large number of common variants.