Sleep and circadian rhythms: pillars of health-a Keystone Symposia report.

The human circadian system consists of the master clock in the suprachiasmatic nuclei of the hypothalamus as well as in peripheral molecular clocks located in organs throughout the body. This system plays a major role in the temporal organization of biological and physiological processes, such as body temperature, blood pressure, hormone secretion, gene expression, and immune functions, which all manifest consistent diurnal patterns. Many facets of modern life, such as work schedules, travel, and social activities, can lead to sleep/wake and eating schedules that are misaligned relative to the biological clock. This misalignment can disrupt and impair physiological and psychological parameters that may ultimately put people at higher risk for chronic diseases like cancer, cardiovascular disease, and other metabolic disorders. Understanding the mechanisms that regulate sleep circadian rhythms may ultimately lead to insights on behavioral interventions that can lower the risk of these diseases. On February 25, 2021, experts in sleep, circadian rhythms, and chronobiology met virtually for the Keystone eSymposium "Sleep & Circadian Rhythms: Pillars of Health" to discuss the latest research for understanding the bidirectional relationships between sleep, circadian rhythms, and health and disease.

Habitual Nightly Fasting Duration, Eating Timing, and Eating Frequency are Associated with Cardiometabolic Risk in Women.

Nightly fasting duration (NFD) and eating timing and frequency may influence cardiometabolic health via their impact on circadian rhythms, which are entrained by food intake, but observational studies are limited. This 1-year prospective study of 116 US women (33 ± 12y, 45% Hispanic) investigated associations of habitual NFD and eating timing and frequency with cardiovascular health (CVH; American Heart Association Life's Simple 7 score) and cardiometabolic risk factors. NFD, eating timing and frequency, and nighttime eating levels were evaluated from 1-week electronic food records completed at baseline and 1 y. In multivariable-adjusted linear regression models, longer NFD was associated with poorer CVH (ß = -0.22, p = 0.016 and ß = -0.22, p = 0.050) and higher diastolic blood pressure (DBP) (ß = 1.08, p < 0.01 and ß = 1.74, p < 0.01) in cross-sectional and prospective analyses, respectively. Later timing of the first eating occasion at baseline was associated with poorer CVH (ß = -0.20, p = 0.013) and higher DBP (ß = 1.18, p < 0.01) and fasting glucose (ß = 1.43, p = 0.045) at 1 y. After adjustment for baseline outcomes, longer NFD and later eating times were also associated with higher waist circumference (ß = 0.35, p = 0.021 and ß = 0.27, p < 0.01, respectively). Eating frequency was inversely related to DBP in cross-sectional (ß = -1.94, p = 0.033) and prospective analyses (ß = -3.37, p < 0.01). In cross-sectional analyses of baseline data and prospective analyses, a higher percentage of daily calories consumed at the largest evening meal was associated with higher DBP (ß = 1.69, p = 0.046 and ß = 2.32, p = 0.029, respectively). Findings suggest that frequent and earlier eating may lower cardiometabolic risk, while longer NFD may have adverse effects. Results warrant confirmation in larger multi-ethnic cohort studies with longer follow-up periods.

Associations of weight cycling with cardiovascular health using American Heart Association's Life's Simple 7 in a diverse sample of women.

Prior research shows that weight cycling is associated with poorer cardiovascular health (CVH). Women experience unique life events (e.g. pregnancy, menopause) which may make them more prone to weight cycling. Examining the influence of weight cycling history (HWC) on CVH, quantified using the American Heart Association's Life's Simple 7 (LS7), may provide novel targets to improve CVH. A cross-sectional sample of 485 women at Columbia University Irving Medical Center (2016-2018) were scored on each LS7 metric (BMI, blood pressure, fasting cholesterol and glucose, physical activity, diet, and smoking): 0 (low), 1 (moderate) or 2 (high). Metric points were summed into a composite LS7 score as a measure of CVH: 0-8 (low), 9-10 (moderate), 11-14 (high). Multivariable-adjusted logistic and linear regression models were used for the associations between HWC and CVH. Most women (73%) reported HWC (range: 0-20); 26% had low CVH and 74% moderate/high CVH. Logistic models showed HWC was associated with higher odds of having poor CVH [OR (95%CI): 2.39 (1.36-4.20)]. Linear models showed each additional weight cycling episode was associated with lower LS7 scores [ß(SE): -0.37 (0.07); p < 0.01]. Associations between HWC and odds of having poor CVH were stronger among pre-menopausal women and those with no pregnancy history (p-interaction = 0.009, 0.004, respectively). In conclusion, HWC was associated with higher odds of poorer CVH with stronger associations seen in pre-menopausal and women with no pregnancy history. These findings suggest that in addition to having a healthy weight, maintaining a consistent weight may be important for achieving optimal CVH, but warrant prospective confirmation.

Association of sleep characteristics with cardiovascular health among women and differences by race/ethnicity and menopausal status: findings from the American Heart Association Go Red for Women Strategically Focused Research Network.

BACKGROUND AND OBJECTIVE: Sleep is an emerging risk factor for cardiovascular disease (CVD) that is not currently included as a cardiovascular health (CVH) metric in the American Heart Association's Life's Simple 7 (AHA LS7). Our objective was to evaluate the association of sleep with CVH in women and examine differences by menopausal status and race/ethnicity. METHODS: Baseline data from the Columbia University AHA Go Red for Women Strategically Focused Research Network were examined. Sleep habits were self-reported using validated questionnaires. A CVH score was computed using AHA LS7 criteria for smoking, diet, physical activity, BMI, blood pressure(BP), total cholesterol, and fasting glucose. Women received a score of 2 (ideal), 1 (intermediate), or 0 (poor) based on their level of meeting each AHA LS7 metric. Multivariable-adjusted regression models were used to evaluate associations of sleep with meeting overall and individual CVH metrics. RESULTS: The analytical sample consisted of n = 507 women (62% minority/Hispanic, mean age:37 y). Participants with adequate sleep duration (≥7 h), good sleep quality, no insomnia nor snoring, and low risk for OSA were more likely to meet >4 of the AHA LS7 metrics (P < .01). Poorer sleep quality (ß = -0.08, P = .002), higher insomnia severity (ß = -0.05, P = .002), snoring (ß = -0.77, P = .0001), and higher risk for OSA (ß = -1.63, P < .0001) were associated with poorer CVH. Insomnia, snoring, and high OSA risk were associated with 69% to >300% higher odds of having poor CVH (P ≤ .03). Associations were stronger in post-menopausal and racial/ethnic minority women. CONCLUSIONS: Better sleep habits were associated with more favorable CVH among women, suggesting that there may be benefit in incorporating sleep assessment into CVD risk screening.

Cardiovascular Disease Disparities in Sexual Minority Adults: An Examination of the Behavioral Risk Factor Surveillance System (2014-2016).

PURPOSE: Investigate sexual orientation differences in cardiovascular disease risk and cardiovascular disease. DESIGN: Cross-sectional. SETTING: The 2014 to 2016 Behavioral Risk Factor Surveillance System. PARTICIPANTS: A total of 395 154 participants. MEASURES: The exposure measure was sexual orientation. Self-report of cardiovascular disease risk factors and cardiovascular disease was assessed. ANALYSIS: Sex-stratified logistic regression analyses to examine sexual orientation differences in cardiovascular disease risk and cardiovascular disease (heterosexuals = reference group). RESULTS: Sexual minority men reported higher rates of mental distress (gay adjusted odds ratio [AOR]: 1.59; bisexual AOR: 1.88) and lifetime depression (gay AOR: 2.48; bisexual: AOR 2.67). Gay men reported higher rates of current smoking (AOR: 1.28), but lower rates of obesity (AOR: 0.82) compared to heterosexual men. Sexual minority women reported higher rates of several cardiovascular risk factors including mental distress (lesbian AOR: 1.37; bisexual AOR: 2.33), lifetime depression (lesbian AOR: 1.96; bisexual AOR: 3.26), current smoking (lesbian AOR: 1.65; bisexual AOR: 1.29), heavy drinking (lesbian AOR: 2.01; bisexual AOR: 2.04), and obesity (lesbian AOR: 1.50; bisexual AOR: 1.29), but were more likely to exercise than heterosexual women (lesbian AOR: 1.34; bisexual AOR: 1.24). Lesbian women reported lower rates of heart attack (AOR: 0.62), but bisexual women had higher rates of stroke than heterosexual women (AOR: 1.46). CONCLUSIONS: Findings can inform the development of prevention efforts to reduce cardiovascular disease risk in sexual minorities.

Associations of Whole and Refined Grain Intakes with Adiposity-Related Cancer Risk in the Framingham Offspring Cohort (1991-2013).

Case-control studies suggest that higher whole grain and lower refined grain intakes are associated with reduced cancer risk, but longitudinal evidence is limited. The objective of this prospective cohort study is to evaluate associations between whole and refined grains and their food sources in relation to adiposity-related cancer risk. Participants were adults from the Framingham Offspring cohort (N = 3,184; ≥18 yr). Diet, measured using a food frequency questionnaire, medical and lifestyle data were collected at exam 5 (1991-95). Between 1991 and 2013, 565 adiposity-related cancers were ascertained using pathology reports. Cox proportional hazards models were used to estimate adjusted hazard ratios and 95% confidence intervals for associations of whole and refined grains with risk of adiposity-related cancers combined and with risk of breast and prostate cancers in exploratory site-specific analyses. Null associations between whole and refined grains and combined incidence of adiposity-related cancers were observed in multivariable-adjusted models (HR: 0.94; 95% CI: 0.71-1.23 and HR: 0.98; 95% CI: 0.70-1.38, respectively). In exploratory analyses, higher intakes of whole grains (oz eq/day) and whole grain food sources (servings/day) were associated with 39% and 47% lower breast cancer risk (HR: 0.61; 95% CI: 0.38-0.98 and HR: 0.53; 95% CI: 0.33-0.86, respectively). In conclusion, whole and refined grains were not associated with adiposity-related cancer risk. Whole grains may protect against breast cancer, but findings require confirmation within a larger sample and in other ethnic groups.

Consumption of Sugars, Sugary Foods, and Sugary Beverages in Relation to Cancer Risk: A Systematic Review of Longitudinal Studies.

High sugar intake may increase cancer risk by promoting insulin-glucose dysregulation, oxidative stress, inflammation, and body adiposity, but epidemiologic evidence is unclear. Associations between dietary sugars and lifestyle-related cancer risk from longitudinal studies were evaluated. We systematically searched PubMed, Embase, and CINAHL and identified 37 prospective cohort studies (1990-2017) reporting multivariable adjusted risk estimates for dietary sugars in relation to cancer. Of 15 and 14 studies on total sugar and sucrose respectively, 11 reported a null association in relation to cancer. Of 14 studies on fructose, 8 reported null associations, and 2 reported protective and 4 reported detrimental associations. In two of five studies on added sugars, a 60-95% increased cancer risk was observed with higher intakes. In 8 of 15 studies on sugary foods and beverages, a 23-200% higher cancer risk was observed with higher sugary beverage consumption. In conclusion, most studies were indicative of a null association, but suggestive detrimental associations were reported for added sugars and sugary beverages.

Consumption of Sugars, Sugary Foods, and Sugary Beverages in Relation to Adiposity-Related Cancer Risk in the Framingham Offspring Cohort (1991-2013).

Background: Higher sugar consumption may increase cancer risk by promoting insulin-glucose dysregulation, oxidative stress, hormonal imbalances, and excess adiposity. This prospective study investigates the association between dietary sugars (fructose and sucrose) and sugary foods and beverages in relation to combined and site-specific (breast, prostate, colorectal) adiposity-associated cancers.Methods: The analytic sample consisted of 3,184 adults, aged 26-84 years, from the Framingham Offspring cohort. Diet data were first collected between 1991 and 1995 using a food frequency questionnaire. Intakes of fructose, sucrose, sugary foods, and sugary beverages (fruit juice and sugar-sweetened beverages) were derived. Participants were followed up until 2013 to ascertain cancer incidence; 565 doctor-diagnosed adiposity-related cancers, including 124 breast, 157 prostate, and 68 colorectal cancers occurred. Multivariable-adjusted Cox proportional hazards models were used to evaluate associations. Tests for interaction with BMI and waist circumference were conducted.Results: No associations were observed between fructose, sucrose, sugary food consumption, and combined incidence of adiposity-related cancers or the examined site-specific cancers. While total consumption of sugary beverages was not associated with site-specific cancer risk, higher intakes of fruit juice were associated with 58% increased prostate cancer risk (HR: 1.58; 95% CI, 1.04-2.41) in multivariable-adjusted models. In exploratory stratified analyses, higher sugary beverage intakes increased overall adiposity-related cancer risk by 59% in participants with excessive central adiposity (HR: 1.59; 95% CI, 1.01-2.50; Ptrend = 0.057).Conclusions: In this cohort of American adults, higher sugary beverage consumption was associated with increased cancer risk among participants with central adiposity.Impact: These analyses suggest that avoiding sugary beverages represents a simple dietary modification that may be used as an effective cancer control strategy. Cancer Prev Res; 11(6); 347-58. ©2018 AACR.

Carbohydrate nutrition and risk of adiposity-related cancers: results from the Framingham Offspring cohort (1991-2013).

Higher carbohydrate intake, glycaemic index (GI), and glycaemic load (GL) are hypothesised to increase cancer risk through metabolic dysregulation of the glucose-insulin axis and adiposity-related mechanisms, but epidemiological evidence is inconsistent. This prospective cohort study investigates carbohydrate quantity and quality in relation to risk of adiposity-related cancers, which represent the most commonly diagnosed preventable cancers in the USA. In exploratory analyses, associations with three site-specific cancers: breast, prostate and colorectal cancers were also examined. The study sample consisted of 3184 adults from the Framingham Offspring cohort. Dietary data were collected in 1991-1995 using a FFQ along with lifestyle and medical information. From 1991 to 2013, 565 incident adiposity-related cancers, including 124 breast, 157 prostate and sixty-eight colorectal cancers, were identified. Cox proportional hazards models were used to evaluate the role of carbohydrate nutrition in cancer risk. GI and GL were not associated with risk of adiposity-related cancers or any of the site-specific cancers. Total carbohydrate intake was not associated with risk of adiposity-related cancers combined or prostate and colorectal cancers. However, carbohydrate consumption in the highest v. lowest quintile was associated with 41 % lower breast cancer risk (hazard ratio (HR) 0·59; 95 % CI 0·36, 0·97). High-, medium- and low-GI foods were not associated with risk of adiposity-related cancers or prostate and colorectal cancers. In exploratory analyses, low-GI foods, were associated with 49 % lower breast cancer risk (HR 0·51; 95 % CI 0·32, 0·83). In this cohort of Caucasian American adults, associations between carbohydrate nutrition and cancer varied by cancer site. Healthier low-GI carbohydrate foods may prevent adiposity-related cancers among women, but these findings require confirmation in a larger sample.

The Relation between Polyphenols and Body Composition in US Hispanics/Latinos: Results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Study of Latinos Nutrition and Physical Activity Assessment Study (SOLNAS).

Background: Polyphenols offer high antioxidant potential that may protect against chronic diseases. Epidemiologic evidence documenting their influence on body composition and obesity risk is limited, particularly among Hispanics/Latinos who are disproportionately prone to obesity. Objectives: The aims of this study were to evaluate cross-sectional associations of urinary polyphenols with body mass index (BMI) and body fat percentage (%BF) in a diverse Hispanic/Latino population and to assess the reliability of polyphenol measurements. Methods: Participants were 442 adults from the Study of Latinos/Nutrition and Physical Activity Assessment Study (SOLNAS) aged 18-74 y. Doubly labeled water was used as an objective recovery biomarker of energy. Polyphenol excretion from 24-h urine samples was assessed. Measures were repeated in a subsample (n = 90) to provide a reliability measure. Anthropometric measures were obtained by trained personnel, and %BF was measured by 18O dilution. Linear regression models were used to evaluate multivariable associations between body composition and polyphenols. Spearman correlation coefficients between BMI and %BF with polyphenols and intraclass correlation coefficients (ICCs) between polyphenol measures were computed. Results: A weak correlation was observed for resveratrol and %BF (r = -0.11, P = 0.02). In multivariable-adjusted regression models, weak inverse associations were observed for resveratrol and urolithin A with %BF [ß ± SE: -0.010 ± 0.004 (P = 0.007) and -0.004 ± 0.002 (P = 0.03), respectively]. For every 50% increase in these urinary polyphenols, there was a 1% and 0.4% decrease in %BF. Urolithin A was inversely associated with BMI (ß ± SE: -0.004 ± 0.002; P = 0.02) and with 5% lower odds of obesity in models not adjusted for total energy expenditure (TEE; OR: 0.95; 95% CI: 0.91, 0.99; P = 0.02). For every 50% increase in urolithin A, there was a 0.4-unit decrease in BMI. Associations were attenuated after adjustment for TEE. Reliability study findings were indicative of weak to moderate correlations (ICCs: 0.11-0.65), representing a degree of within-person variation in polyphenol biomarkers. Conclusions: Although associations were weak, resveratrol and urolithin A were inversely associated with obesity. Repeated polyphenol urine measures could clarify their long-term impact on body adiposity.

Consumption of whole grains and cereal fiber in relation to cancer risk: a systematic review of longitudinal studies.

CONTEXT: Evidence from previous reviews is supportive of the hypothesis that whole grains may protect against various cancers. However, the reviews did not report risk estimates for both whole grains and cereal fiber and only case-control studies were evaluated. It is unclear whether longitudinal studies support this conclusion. OBJECTIVE: To evaluate associations between whole grains and cereal fiber in relation to risk of lifestyle-related cancers data from longitudinal studies was evaluated. DATA SOURCES: The following 3 databases were systematically searched: PubMed, EMBASE, and Cochrane CENTRAL. STUDY SELECTION: A total of 43 longitudinal studies conducted in Europe and North America that reported multivariable-adjusted risk estimates for whole grains (n = 14), cereal fiber (n = 23), or both (n = 6) in relation to lifestyle-related cancers were included. DATA EXTRACTION: Information on study location, cohort name, follow-up duration, sample characteristics, dietary assessment method, risk estimates, and confounders was extracted. DATA SYNTHESIS: Of 20 studies examining whole grains and cancer, 6 studies reported a statistically significant 6%-47% reduction in risk, but 14 studies showed no association. Of 29 studies examining cereal fiber intake in relation to cancer, 8 showed a statistically significant 6%-49% reduction in risk, whereas 21 studies reported no association. CONCLUSIONS: This systematic review concludes that most studies were suggestive of a null association. Whole grains and cereal fiber may protect against gastrointestinal cancers, but these findings require confirmation in additional studies.

Insulin receptor variants and obesity-related cancers in the Framingham Heart Study.

PURPOSE: The insulin-signaling pathway plays a pivotal role in cancer biology; however, evidence of genetic alterations in human studies is limited. This case-control study nested within the Framingham Heart Study (FHS) examined the association between inherited genetic variation in the insulin receptor (INSR) gene and obesity-related cancer risk. METHODS: The study sample consisted of 1,475 controls and 396 cases from the second familial generation of the FHS. Participants who provided consent were genotyped. Nineteen single-nucleotide polymorphisms (SNPs) in the INSR gene were investigated in relation to risk of obesity-related cancers combined and breast, prostate and colorectal cancers. Generalized estimation equation models controlling for familial correlations and include age, sex, smoking and body mass index as covariates, assuming additive models, were used. RESULTS: Three SNPs, rs2059807, s8109559 and rs919275, were significantly associated with obesity-related cancers (p value < 0.02) with the most significantly associated SNP being rs2059807 (p value = 0.008). Carriers of two copies of SNP rs2059807 risk allele T were significantly less prevalent among subjects with obesity-related cancers [f(TT)cases = 14 vs. f(TT)controls = 18 %; OR 1.23]. In exploratory analyses evaluating site-specific cancers, the INSR rs2059807 association with these cancers was consistent with that observed for the main outcome (ORs colorectal cancer = 1.5, breast cancer = 1.29, prostate = 1.06). There was no statistically significant interaction between the INSR-SNP and blood glucose in relation to obesity-related cancer. CONCLUSIONS: The INSR gene is implicated in obesity-related cancer risk, as 3 of 19 SNPs were nominally associated, after false discovery rate (FDR) correction, with the main outcome. Risk allele homozygotes (rs2059807) were less prevalent among subjects with obesity-related cancer. These results should be replicated in other populations to confirm the findings.

Concordance with World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) guidelines for cancer prevention and obesity-related cancer risk in the Framingham Offspring cohort (1991-2008).

PURPOSE: This prospective cohort study evaluates associations between healthful behaviors consistent with WCRF/AICR cancer prevention guidelines and obesity-related cancer risk, as a third of cancers are estimated to be preventable. METHODS: The study sample consisted of adults from the Framingham Offspring cohort (n = 2,983). From 1991 to 2008, 480 incident doctor-diagnosed obesity-related cancers were identified. Data on diet, measured by a food frequency questionnaire, anthropometric measures, and self-reported physical activity, collected in 1991 was used to construct a 7-component score based on recommendations for body fatness, physical activity, foods that promote weight gain, plant foods, animal foods, alcohol, and food preservation, processing, and preparation. Multivariable Cox regression models were used to estimate associations between the computed score, its components, and subcomponents in relation to obesity-related cancer risk. RESULTS: The overall score was not associated with obesity-related cancer risk after adjusting for age, sex, smoking, energy, and preexisting conditions (HR 0.94, 95 % CI 0.86-1.02). When score components were evaluated separately, for every unit increment in the alcohol score, there was 29 % lower risk of obesity-related cancers (HR 0.71, 95 % CI 0.51-0.99) and 49-71 % reduced risk of breast, prostate, and colorectal cancers. Every unit increment in the subcomponent score for non-starchy plant foods (fruits, vegetables, and legumes) among participants who consume starchy vegetables was associated with 66 % reduced risk of colorectal cancer (HR 0.44, 95 % CI 0.22-0.88). CONCLUSIONS: Lower alcohol consumption and a plant-based diet consistent with the cancer prevention guidelines were associated with reduced risk of obesity-related cancers in this population.

Availability of Outpatient Clinical Nutrition Services for Patients With Cancer Undergoing Treatment at Comprehensive Cancer Centers.

PURPOSE: The mission of US Comprehensive Cancer Centers (CCC) is to reduce cancer morbidity and mortality. The type of clinical nutrition services available to outpatients seeking treatment at CCCs is unknown. The purpose of this cross-sectional study was to determine the prevalence and types of outpatient clinical nutrition services available at CCCs. METHODS: A list of the National Cancer Institute (NCI) -designated CCCs was compiled. A telephone survey that queried clinical nutrition services available to outpatients undergoing treatment was developed. The survey was conducted with clinical nutrition personnel during usual working hours between April and October 2012. RESULTS: Of the 40 CCCs, 32 (80%) completed the survey. Thirty CCCs offered referral- or consult-based services with a clinical nutrition professional such as a registered dietitian (RD). Other services included nutrition classes (56%), nutrition pamphlets (94%), and counseling by non-nutrition health care providers (81%). Twenty-three of the centers monitored patients regularly, but less than half followed a clinical nutrition protocol such as those established by the Academy of Nutrition and Dietetics. Referral-based services were provided for cancers with a high prevalence of malnutrition, such as head and neck and GI, with most monitoring patients regularly but less than half using evidence-based protocols. CONCLUSION: CCCs rely on referral-based clinical nutrition service, which are not consistently a part of multidisciplinary care. An in-depth comparison of clinical nutrition services among other approaches to cancer care, including a comparison of clinical outcomes among these different approaches, is needed.

Treatment and outcomes in diabetic breast cancer patients.

Effective breast cancer management is more complex with diabetes present and may contribute to poor outcomes. Therefore, we conducted two simultaneous systematic reviews to address the association of diabetes with (1) treatment patterns in breast cancer patients and (2) breast cancer recurrence rates or breast cancer-specific and all-cause mortality. We searched major databases for English language peer-reviewed studies through November 2013, which addressed either of the above research questions, following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) method. Analyses compared treatment patterns or health outcomes for breast cancer subjects with and without diabetes. We used STROBE quality criteria and conducted a random-effects meta-analysis of all-cause mortality. The review yielded 11 publications for question 1 and 26 for question 2, with nine overlapping. Treatment studies showed chemotherapy was less likely in patients with diabetes. Of 22 studies, 21 assessing all-cause mortality indicated a statistically significant increased overall mortality for patients with diabetes (hazard ratios: 0.33-5.40), with meta-analysis of eligible studies indicating a 52 % increased risk. Nine studies assessing breast cancer-specific mortality had inconsistent results, with five showing significantly increased risk for diabetes patients. Results were inconsistent for recurrence and metastases. The majority of studies reported detrimental associations between diabetes and optimal treatment or all-cause mortality among women with breast cancer. Divergence in variable and outcomes inclusion and definitions, potential participation bias in individual studies, and differing analytic methods make inferences difficult. This review illuminates the importance of the impact of diabetes on breast cancer patients and explicitly recognizes that co-management of conditions is necessary to prevent excess morbidity and mortality.

Dietary fat in breast cancer survival.

Laboratory evidence suggests a plausible role for dietary fat in breast cancer pathophysiology. We conducted a systematic literature review to assess the epidemiological evidence on the impact of total dietary fat and fat subtypes, measured pre- and/or postcancer diagnosis, in relation to breast cancer-specific and all-cause mortality among breast cancer survivors. Studies were included if they were in English, had a sample size ≥200, and presented the hazard ratio/rate ratio for recurrence, disease-specific mortality, or all-cause mortality (n = 18). Although the results are mixed, most studies suggested that higher saturated fat intake prediagnosis was associated with increased risk of breast cancer-specific and all-cause mortality. Postdiagnostic trans fat intake was associated with a 45% and 78% increased risk of all-cause mortality. Higher monounsaturated fat intake before and after diagnosis was generally associated with increased risk of all-cause and breast cancer-specific mortality, albeit the majority of the studies were statistically nonsignificant. Two studies evaluating omega-3 fat intake suggested an inverse association with all-cause mortality. Although there were too few studies on fat subtypes to draw definitive conclusions, high consumption of saturated fat may exert a detrimental effect on breast cancer-specific and all-cause mortality, whereas omega-3 fat may be beneficial. The inconsistent and limited evidence warrants research to assess the impact of consumption of fat subtypes on breast cancer recurrence and mortality.