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Insulin resistance and hyperinsulinemia play important roles in the progression of multiple chronic disease and conditions. Diet modulates insulin response; however, evidence is limited regarding whether diets with higher insulinemic potential increase the risk of invasive breast cancer.We aimed to prospectively evaluate the association between a food-based empirical dietary index for hyperinsulinemia (EDIH) and the incidence of invasive breast cancer.We prospectively followed 76,686 women from the Nurses' Health Study (NHS; 1984-2016) and 93,287 women from the Nurses' Health Study II (NHSII; 1991-2017). Diet was assessed by food-frequency questionnaires every 4 y. The insulinemic potential of diet was evaluated using the previously established EDIH based on circulating C-peptide concentrations. Higher scores indicate higher insulinemic potential of the diet. Covariates included reproductive, hormonal, and anthropometric factors (height and BMI at age 18 y); race; socioeconomic status; total alcohol intake; total caloric intake; and physical activity.During 4,216,106 person-years of follow-up, we documented 10,602 breast cancer cases (6689 NHS, 3913 NHSII). In the pooled multivariable-adjusted analyses, women in the highest, compared with the lowest, EDIH quintile (Q) were at higher breast cancer risk (HRQ5 vs. Q1 = 1.15; 95% CI: 1.07, 1.24; P-trend 0.01). Although heterogeneity by estrogen receptor (ER) status was nonsignificant, the strongest association between EDIH and breast cancer was observed for ER-negative tumors (HRQ5 vs. Q1 = 1.21; 95% CI: 1.00, 1.46; P-trend = 0.02). Among tumor molecular subtypes, the strongest associations were observed for human epidermal growth factor receptor 2 (HER2)-enriched tumors (HRQ5 vs. Q1 = 1.62; 95% CI: 1.01, 2.61; P-trend = 0.02).A dietary pattern contributing to hyperinsulinemia and insulin resistance was associated with greater breast cancer risk, especially ER-negative and HER2-enriched tumors. Our findings suggest that dietary modifications to reduce insulinemic potential may reduce the risk of breast cancer.

Avocados contain nutrients and phytochemicals that make it promising for cancer prevention, and chemopreventive properties have been demonstrated in prior studies. Prospective studies on avocado consumption and cancer risk have yet to be conducted. This study included data from 45,289 men in the Health Professionals Follow-Up Study (HPFS, 1986–2016) and 67,039 women in the Nurses’ Health Study (NHS, 1986–2014). Avocado consumption was assessed using validated food frequency questionnaires every 4 years. Cox proportional hazards models calculated multivariable HRs and 95% confidence intervals (CI) for associations between avocado consumption and risk of total and site-specific cancers in each cohort. In HPFS, consumption of ≥1 weekly serving of avocados was associated with decreased risk of total (HR, 0.85; 95% CI, 0.80–0.91), colorectal (HR, 0.71; 95% CI, 0.59–0.85), lung (HR, 0.71; 95% CI, 0.57–0.90), and bladder cancer (HR, 0.72; 95% CI, 0.57–0.90). In NHS, avocado consumption was associated with increased risk of breast cancer (HR, 1.21; 95% CI, 1.07–1.37). No associations were observed between avocado consumption and risk of total cancer (HR, 1.06; 95% CI, 0.98–1.14) or other site-specific cancers in NHS. Considering the surprising breast cancer finding, analyses were repeated using data from 93,230 younger women in the parallel NHSII (1991–2017). In NHSII, avocado consumption was not associated with breast cancer risk (HR, 0.93; 95% CI, 0.76–1.13). Overall, avocado consumption may be associated with reduced risk of total and some site-specific cancers in men. The positive association with breast cancer risk in NHS was not seen in the younger NHSII.Prevention Relevance:The results of this prospective study suggest that avocado consumption may be associated with decreased risk of total and some site-specific cancers in men.See related Spotlight, p. 187

Supplementary Table S1 shows associations of avocado consumption and risk of cancer excluding current smokers, with similar results as the overall cohort.

Background: Insulin resistance and hyperinsulinemia play important roles in the progression of multiple chronic disease and conditions. Diet modulates insulin response; however, evidence is limited regarding whether diet with higher insulinemic potential is associated with invasive breast cancer risk.Objectives: We prospectively evaluated the association between adherence to a food-based empirical dietary index for hyperinsulinemia (EDIH) and the incidence of invasive breast cancer.Methods: We prospectively followed 76,595 women from the Nurses’ Health Study (NHS, 1984-2016) and 93,295 women from the Nurses’ Health Study II (NHSII, 1991-2017). Diet was assessed by food frequency questionnaires every 4 years. The insulinemic potential of diet was evaluated using the EDIH that was pre-defined based on circulating C-peptide concentrations. Higher scores indicate higher insulinemic potential, while lower scores indicate lower insulinemic potential.Results: During 4,215,162 person-years of follow-up, we documented 10,595 breast cancer cases (6,639 NHS; 3,914 NHSII). Being in the highest, compared with the lowest, EDIH quintile was associated with higher breast cancer risk (HRQ5vsQ1 1.18; 95% CI 1.10, 1.27; P-trend Citation Format: Andrea Romanos-Nanclares, Walter C. Willett, Bernard A. Rosner, Rulla M. Tamimi, Fred K. Tabung, Michelle D. Holmes, Wendy Y Chen, A. Heather Eliassen. Insulinemic potential of diet and risk of total and subtypes of breast cancer among US women [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-09-06.

Background Although unopposed estrogen exposure is considered a major driver of endometrial carcinogenesis, chronic inflammation and insulin resistance and hyperinsulinemia are also major endometrial cancer risk factors. However, it is unclear whether diets with inflammatory or insulinemic potential are associated with risk of endometrial cancer. Methods We followed 48 330 women from the Nurses’ Health Study (1984-2016) and 85 426 women from the Nurses’ Health Study II (1989-2017). Using food frequency questionnaires, we calculated repeated measures of empirical dietary inflammatory pattern (EDIP) and empirical dietary index for hyperinsulinemia (EDIH) scores, which characterize the potential of the whole diet to modulate circulating biomarkers of inflammation or C-peptide, respectively. We used multivariable-adjusted Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for type I endometrial cancer risk. Results We documented 1462 type I endometrial cancer cases over 2 823 221 person-years of follow-up. In the pooled multivariable-adjusted analyses, women in the highest compared with lowest quintiles were at higher risk of type I endometrial cancer (EDIP HRQ5vsQ1 = 1.46, 95% CI = 1.24 to 1.73; Ptrend < .001; EDIH HRQ5vsQ1 = 1.58, 95% CI = 1.34 to 1.87; Ptrend < .001). Additional adjustment for body mass index attenuated the associations (EDIP HR = 1.03, 95% CI = 0.87 to 1.22; EDIH HR = 1.01, 95% CI = 0.85 to 1.21), and mediation analyses showed that body mass index may explain 60.4% (95% CI = 37.4% to 79.6%; P < .001) and 71.8% (95% CI = 41.0% to 90.4%; P < .001) of the association of endometrial cancer with EDIP and EDIH, respectively. Conclusions In this large cohort study, higher dietary inflammatory and insulinemic potential were each associated with increased endometrial cancer incidence, and this association may be almost entirely mediated by adiposity.

Background: Plant-based diets have been associated with lower risk of various diseases, including type 2 diabetes, cardiovascular disease, and other cardiometabolic risk factors. However, the association between plant-based diet quality and breast cancer remains unclear. Methods: We prospectively followed 76,690 women from the Nurses' Health Study (NHS, 1984–2016) and 93,295 women from the NHSII (1991–2017). Adherence to an overall plant-based diet index (PDI), a healthful PDI (hPDI), and an unhealthful PDI (uPDI) was assessed using previously developed indices. Cox proportional hazards models were used to estimate HR and 95% confidence intervals (CI) for incident invasive breast cancer. Results: Over 4,841,083 person-years of follow-up, we documented 12,482 incident invasive breast cancer cases. Women with greater adherence to PDI and hPDI were at modestly lower risk of breast cancer [(HRQ5 vs. Q1, 0.89; 95% CI, 0.84–0.95); (HRQ5 vs. Q1, 0.89; 95% CI, 0.83–0.94)]. We observed significant heterogeneity by estrogen receptor (ER) status, with the strongest inverse association between hPDI and breast cancer observed with ER-negative tumors [HRQ5 vs. Q1, 0.77; 95% CI, 0.65–0.90; Ptrend < 0.01]. We also found an inverse association between extreme quintiles of healthy plant foods and ER-negative breast cancer [HR, 0.74; 95% CI, 0.61–0.88; Ptrend < 0.01]. Conclusions: This study provides evidence that adherence to a healthful plant-based diet may reduce the risk of breast cancer, especially those that are more likely to be aggressive tumors. Impact: This is the first prospective study investigating the relation between healthful and unhealthful plant-based dietary indices and risk of total and subtype-specific breast cancer.

Background: Dietary patterns promoting chronic inflammation, including the empirical dietary inflammatory pattern (EDIP), have been shown to strongly influence risk of weight gain, type 2 diabetes, cardiovascular disease, and colorectal cancer. However, it is unclear if this dietary pattern is associated with other tumors in which the mechanisms are not totally understood such as breast cancer. Methods: We prospectively followed 76,295 women from the Nurses’ Health Study (NHS, 1984-2016) and 91,078 women from the Nurses’ Health Study II (NHSII, 1991-2017). Diet was assessed by food frequency questionnaires (FFQs) every 4 years. The inflammatory potential of diet was evaluated using the previously established EDIP based on plasma C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha receptor 2 (TNF-αR2). Higher scores indicate higher inflammatory potential of the diet. Results: During 4,153,676 person-years of follow-up, we documented 10,632 invasive breast cancer cases (6,807 NHS; 3,825 NHSII). In the pooled multivariable-adjusted analyses, women in the highest, compared with the lowest, EDIP quintile were at higher breast cancer risk (HRQ5vsQ1=1.12; 95% CI 1.05, 1.20; P-trend< 0.001). This association was attenuated after adjusting for weight change since age 18 y, although it remained significant (HRQ5vsQ1=1.07; 95% CI 1.00, 1.14; P-trend=0.01). In subtype analyses, we found evidence that the inflammatory potential of diet influenced breast cancer risk differentially by ER status (P-heterogeneity=0.038) and by molecular phenotype (P-heterogeneity=0.007), with the association between EDIP and breast cancer limited to ER-negative tumors (HRQ5vsQ1=1.31; 95% CI: 1.11, 1.55; P-trend=0.002; for ER-positive tumors, HR Q5vsQ1=1.03; 95% CI, 0.96, 1.12;P-trend=0.10) and basal-like tumors (HRQ5vsQ1=1.78; 95% CI: 1.19, 2.65; P-trend=0.004). Further adjustment for weight change since age 18 y did not materially alter the association for these subtypes. Conclusions: Dietary patterns with high potential to contribute to chronic systemic inflammation, based on higher EDIP scores, were associated with a modestly increased risk of breast cancer, which was more pronounced for ER-negative and basal-like breast tumors. Citation Format: Andrea Romanos-Nanclares, Walter C Willett, Bernard A Rosner, Daniel G Stover, Sarah Asad, Sagar Sardesai, Michelle D Holmes, Wendy Y Chen, Rulla M. Tamimi, Fred K Tabung, A Heather Eliassen. Proinflammatory Dietary Patterns and Risk of Total and Subtypes of Breast Cancer Among US Women [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-03-14.

AIM The association between caesarean delivery and the risk of overweight/obesity in the offspring has been previously reported using conventional measures of association (relative risks or odds ratios). We aimed at refining the existing evidence by calculating the marginal effect of the exposure and estimating the unmeasured residual confounding. METHODS In the 'SEguimiento del Nino para un Desarrollo Optimo' Project, a dynamic multipurpose paediatric cohort study, we collected information from parents through self-administered online questionnaires. We estimated the offspring's risk of overweight/obesity at age 4-6 years, associated with the type of delivery through marginal effect of the exposure. Unmeasured residual confounding was assessed using the E-value. RESULTS Among 407 participants (mean-age: 5.0 years (standard deviation: 0.9)), 86 (21.1%) were born by caesarean delivery. Children born by caesarean delivery had higher odds of overweight/obesity than those born vaginally. Subgroup analyses showed similar results. The multivariable adjusted marginal effect showed that caesarean delivery was associated with an 8.0% (95% confidence interval: 0.2-15.7) absolute increase in the prevalence of overweight/obesity. The estimated residual confounding showed an E-value of 4.03, higher than the OR obtained for all the confounding factors we accounted for. CONCLUSIONS Caesarean delivery was associated with an 8% absolute increase in the risk of overweight/obesity that is very unlikely explained by residual confounding.

OBJECTIVES: Beyond the quantity of carbohydrate intake, further research is needed on the relevance of carbohydrate quality and chronic conditions. No previous longitudinal study has assessed the association between an integrated multi-dimensional index for carbohydrate intake quality and the risk of breast cancer (BC). Thus, we evaluated the association between an a priori defined carbohydrate quality index (CQI) and the incidence of BC in a Mediterranean cohort study. METHODS: We used a validated semi-quantitative 136-item food-frequency questionnaire (FFQ) to evaluate the CQI at baseline, as previously described (PMID: 31,868,210), based on 4 criteria: dietary fiber intake, glycemic index, whole grain/total grain ratio, and solid carbohydrate/total carbohydrate ratio), in 10,812 middle-aged women. RESULTS: During a median follow-up of 11.8 years, we confirmed 101 incident cases of BC. A higher CQI (fourth quartile) was associated with a lower risk of BC [HR (Q4 vs. Q1) 0.39 (95% CI 0.17, 0.87) p for trend: 0.049]. When we additionally included probable incident cases (n = 190) this association between CQI and BC persisted with a relative risk reduction of 48% for the overall sample of women [HR (Q4 vs. Q1) 0.52, 95% CI 0.31, 0.89; p for trend: 0.034]. Furthermore, when we stratified by menopausal status, we found a significant inverse association between the CQI and premenopausal BC for both confirmed (HR (T3 vs. T1) 0.32, 95% CI 0.10, 1.00) and probable (HR (T3 vs. T1) 0.46, 95% CI 0.22, 0.96) cases. CONCLUSIONS: In this Mediterranean cohort, a better quality of dietary carbohydrate intake showed a significant inverse association with the incidence of BC, particularly among premenopausal women, which suggests that strategies for cancer prevention should focus, in relation to diet, on the quality of this macronutrient. FUNDING SOURCES: The SUN Project has been supported by the Institute of Health Carlos III, the European Regional Development Fund, the Navarra Regional Government, and the University of Navarra.

The global growing rates of cognitive decline and dementia, together with the absence of curative therapies for these conditions, support the interest in researching potential primary prevention interventions, with particular focus on dietary habits. The aim was to assess the association between polyphenol intake and 6-year change in cognitive function in the ‘Seguimiento Universidad de Navarra’ (SUN) Project, a Spanish prospective cohort study. Changes (final – initial) in cognitive function were evaluated in a subsample of 806 participants (mean age 66 (sd 5) years, 69·7 % male) of the SUN Project using the validated Spanish Telephone Interview for Cognitive Status-modified score. Polyphenol intake was derived from a validated semi-quantitative FFQ and matching food composition data from the Phenol-Explorer database. Multivariable linear regression models were used to evaluate the association between total polyphenol intake, polyphenol subclasses and cognitive changes. No significant association between total polyphenol intake and changes in cognitive function was found. However, a higher intake of lignans (βQuintile (Q) 5 v. Q1 0·81; 95 % CI 0·12, 1·51; Ptrend = 0·020) and stilbenes (βQ5 v. Q1 0·82; 95 % CI 0·15, 1·49; Ptrend = 0·028) was associated with more favourable changes in cognitive function over time, particularly with respect to immediate memory and language domains. Olive oil and nuts were the major sources of variability in lignan intake, and wine in stilbene intake. The results suggest that lignan and stilbene intake was associated with improvements in cognitive function.

BACKGROUND: Breast cancer is the leading type of cancer in women worldwide. Some factors, like leisure-time physical activity (LTPA), have been inversely associated with the risk of breast cancer. Nevertheless, evidence on the influence of sedentary lifestyles, LTPA, and their combined exposure on breast cancer risk is still limited. We aimed to assess sedentary behavior and recreational PA in relation to subsequent risk of breast cancer in a Mediterranean cohort. METHODS: The SUN Project is a Spanish dynamic prospective cohort of university graduates initiated in 1999. The baseline assessment included a validated questionnaire on LTPA and sedentary habits. Participants completed biennial follow-up questionnaires, which inquired about medical diagnosis of breast cancer. Self-reported information was confirmed with medical reports; self-reported cases pending confirmation were added to confirmed cases and together they were labeled as "probable cases". For our analyses, we included 10,812 women, with a median follow-up of 11.8 years. Multivariable Cox regression models were used to estimate the hazard ratio (HR) for breast cancer according to 3 categories of weekly METs-hours of LTPA (low: 0-6, medium: 6.1-16.5, high >16.5), h/d of TV watching (2 h) and an 8-item PA Score (low: RESULTS: Mean baseline age of our participants was 34.7 years (SD: 10.6 years). Among 115,802 women-years of follow-up, we identified 190 probable incident cases of breast cancer, out of which we confirmed 101. In multivariable-adjusted analyses, women in the highest category of LTPA showed a significantly lower risk of breast cancer (HR=0.55; 95% CI: 0.34-0.89) compared to women in the lowest category. Women watching >2 h/d of TV had a significantly higher risk of breast cancer (HR=1.71; 95% CI:1.05-2.78) compared to women who watched CONCLUSION: In this Mediterranean cohort, women in the highest leisure-time PA categories showed a significant decrease in breast cancer risk. More than 2 h/day of TV watching was associated with a higher risk of breast cancer development. The harmful effect of TV watching persisted despite the practice of >6 MET-h/week of PA. Hazard ratio (HR) and 95% confidence interval (95% CI) of breast cancer according to levels of LTPA.MET-h/week categoriesLow (0-6)Medium (6.1-16.5)High (>16.5)Cases/ Women-years31/2359032/3963238/52580Multivar. adjusted1 (ref)0.61 (0.37 - 1.00)0.55 (0.34 - 0.89)Hours/day of TV watching< 1 hour1-2 hours>2 hoursCases/ Women-years30/3546930/4484241/35491Multivar. adjusted1 (ref)0.92 (0.55 - 1.54)1.71 (1.05 - 2.78)Joint classificationMET>6MET>6MET2hTV2hCases/ Women-years42/6471728/2749518/1559413/7996Multivar. adjusted1 (ref)1.77 (1.09 - 2.88)1.73 (0.99 - 3.03)3.05(1.61 - 5.77)Physical Activity ScoreLow ( Citation Format: Rodrigo Sánchez-Bayona, Itziar Gardeazabal, Cesar Ignacio Fernandez-Lazaro, Miguel Angel Martinez-Gonzalez, Andrea Romanos-Nanclares, Ismael Alvarez-Alvarez, Alfredo Gea, Marta Santisteban, Estefanía Toledo. Physical activity, sedentary behaviour, and risk of breast cancer: Results from the SUN (‘Seguimiento Universidad de Navarra’) project [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-08-04.

Breast cancer prevalence is growing worldwide. Many factors, such as diet and lifestyle could be determinants of the incidence of breast cancer. Coffee has been extensively studied in relation to several chronic diseases because of its multiple effects in health maintenance and its elevated consumption. We studied the relationship between coffee intake and breast cancer risk in the SUN (Seguimiento Universidad de Navarra) prospective cohort. We evaluated 10,812 middle-aged, Spanish female university graduates from the SUN Project, initially free of breast cancer. Coffee consumption was assessed with a 136-item validated food-frequency questionnaire (FFQ). Incident breast cancer cases were confirmed by a trained oncologist using medical records and by consultation of the National Death Index. We fitted Cox regression models to assess the relationship between baseline categories of coffee consumption and the incidence of breast cancer during follow-up. We stratified the analysis by menopausal status. During 115,802 person-years of follow-up, 101 new cases of breast cancer were confirmed. Among postmenopausal women, more than 1 cup of coffee per day was associated with a lower incidence of breast cancer (HR 0.44; 95% confidence interval: 0.21, 0.92) in the fully adjusted model, compared to women who consumed one cup of coffee or less per day. We observed no significant differences in regard to premenopausal women. Even though the number of cases was low, slight indications of an inverse association between coffee consumption and breast cancer risk among postmenopausal women were observed. Further longitudinal studies are warranted to confirm this finding.

Background The association between parental perception of child’s weight and their attitudes towards his/her dietary habits has not been reported yet. This study aimed to assess the association between parental underestimation of child’s weight and parental attitudes towards child’s dietary habits. Methods We conducted a cross-sectional analysis of SENDO cohort participants recruited between January 2015 and June 2020. All information was collected through online questionnaires completed by parents. We calculated crude and multivariable-adjusted odds ratio (OR) and 95% confidence intervals (CI) for unhealthy attitudes towards child’s dietary habits associated with parental underestimation of child’s weight. Results Sixteen percent of children in the SENDO project had parents who underestimated their weight. Parents who underestimated their child’s weight status were more likely to have unhealthy attitudes toward his/her dietary habits [OR 3.35; 95% CI (1.71–6.53)]. Conclusions Parental underestimation of child's weight was associated with unhealthy attitudes towards child’s dietary habits. Pediatricians and public health practitioners should pay attention to the parental perception of child’s weight to identify parents who underestimate it as an at-risk group in which to inquire about lifestyle and dietary habits.

BACKGROUND: Whether consumption of sugar-sweetened beverages (SSBs) or artificially sweetened beverages (ASBs) is associated with the risk of breast cancer is of public health interest. OBJECTIVES: We sought to evaluate associations between consumption of SSBs and ASBs and risks of total and subtype-specific breast cancer. METHODS: We followed 82,713 women from the Nurses’ Health Study (1980 to 2016) and 93,085 women from the Nurses’ Health Study II (1991 to 2017). Cumulatively averaged intakes of SSBs and ASBs from FFQs were tested for associations with incident breast cancer cases and subtypes using Cox regression models. We also evaluated the associations stratified by menopausal status, physical activity, BMI, and alcohol intake. RESULTS: We documented 11,379 breast cancer cases during 4,655,153 person-years of follow-up. Consumption of SSBs or ASBs was not associated with total breast cancer risk: pooled HRs comparing extreme categories (≥1/day compared with

Evidence is still limited on the influence of sedentary lifestyles on breast cancer (BC) risk. Also, prospective information on the combined effects of both sedentariness and leisure-time physical activity (LTPA) is scarce. We aimed to assess the association of higher sedentary behavior and LTPA (separately and in combination) with the risk of BC in a middle-aged cohort of university graduates. The SUN Project is a follow-up study initiated in 1999 with recruitment permanently open. Baseline assessments included a validated questionnaire on LTPA and sedentary habits. Subsequently, participants completed biennial follow-up questionnaires. Multivariable adjusted Cox models were used to estimate the hazard ratios (HR) for incident BC according to LTPA, TV-watching, the joint classification of both, and a combined 8-item multidimensional active lifestyle score. We included 10,812 women, with 11.8 years of median follow-up of. Among 115,802 women-years of follow-up, we confirmed 101 incident cases of BC. Women in the highest category of LTPA (>16.5 MET-h/week) showed a significantly lower risk of BC (HR = 0.55; 95% CI: 0.34–0.90) compared to women in the lowest category (≤6 MET/h-week). Women watching >2 h/d of TV sh owed a higher risk (HR = 1.67; 95% CI:1.03–2.72) than those who watched TV 2 h/d may substantially increase BC risk, independently of each other.

Objective:To assess whether higher adherence to the traditional Mediterranean diet (MedDiet) was associated with lower consumption of ultra-processed foods (UPF) and lower free sugar intake.Design:Cross-sectional analysis of baseline information among participants in the SENDO project, a Spanish paediatric cohort. Dietary information was collected through a semi-quantitative FFQ. Food items were classified according to the NOVA classification. Adherence to the MedDiet was evaluated through the KIDMED index.Setting:Spain.Participants:Three hundred eight-six children (52 % boys) with a mean age of 5·3 years old (sd 1·0) were included in the analysis.Results:74·4 % of the children had moderate adherence to the MedDiet (mean KIDMED score: 5·9 points; sd 1·7) and overall, 32·2 % of the total energy intake came from UPF. Each two additional points in the KIDMED score was associated with 3·1 % (95 % CI 2·1, 4·0) lower energy intake from UPF. Compared to those with low adherence to the MedDiet, children with medium and high adherence reported 5·0 % (95 % CI 2·2, 7·7) and 8·5 % (95 % CI 5·2, 11·9) lower energy intake from UPF, respectively. We also found that 71·6 % of the variability in free sugar intake was explained by the variability in UPF consumption.Conclusions:Adherence to the traditional MedDiet was inversely associated with energy intake from UPF. Furthermore, most of the variability in free sugar intake was explained by the variability of UPF consumption. Public health strategies are needed to strengthen the adherence to the MedDiet in pre-schoolers while regulating the production, marketing and advertising of UPF.

Epidemiological evidence concerning the relationship between calcium and vitamin D intake and breast cancer (BC) is inconclusive. Moreover, the association according to menopausal status remains unclear. We aimed to assess whether total intakes from dietary and supplemental sources of calcium and vitamin D were associated with the incidence of BC in a Mediterranean cohort. We prospectively evaluated the association between intakes of calcium and vitamin D and BC risk among 10,812 women in the Seguimiento Universidad de Navarra (SUN) Project, a Spanish cohort of university graduates. During a mean follow-up of 10.7 years, 101 incident BC cases were confirmed. Evidence of a non-linear association between total calcium intake and BC risk was found (Pnon-linearity = 0.011) with risk reductions associated with higher intake up to approximately 1400 mg/day. Moderate intake [Tertile 2 (T2)] of total calcium was associated with lower overall BC risk [HR for T2 vs. Tertile 1 (T1): 0.55; 95% CI 0.33–0.91] and also among postmenopausal women (HRT2 vs. T1 = 0.38; 95% CI 0.16–0.92). Intake of vitamin D was not associated with BC risk. Our findings suggest an L-shaped association between total calcium intake and BC incidence. Moderate calcium intake may be associated with lower BC risk among overall and postmenopausal women, but not among premenopausal women. No evidence for any association between vitamin D intake and BC was found. Adherence to current guidelines recommendations for calcium intake may help to reduce BC risk.

Dietary polyphenol intake is associated with improvement of metabolic disturbances. The aims of the present study are to describe dietary polyphenol intake in a population with metabolic syndrome (MetS) and to examine the association between polyphenol intake and the components of MetS. This cross-sectional analysis involved 6633 men and women included in the PREDIMED (PREvenci&oacute, n con DIeta MEDiterranea-Plus) study. The polyphenol content of foods was estimated from the Phenol-Explorer 3.6 database. The mean of total polyphenol intake was 846 &plusmn, 318 mg/day. Except for stilbenes, women had higher polyphenol intake than men. Total polyphenol intake was higher in older participants (&gt, 70 years of age) compared to their younger counterparts. Participants with body mass index (BMI) &gt, 35 kg/m2 reported lower total polyphenol, flavonoid, and stilbene intake than those with lower BMI. Total polyphenol intake was not associated with a better profile concerning MetS components, except for high-density lipoprotein cholesterol (HDL-c), although stilbenes, lignans, and other polyphenols showed an inverse association with blood pressure, fasting plasma glucose, and triglycerides. A direct association with HDL-c was found for all subclasses except lignans and phenolic acids. To conclude, in participants with MetS, higher intake of several polyphenol subclasses was associated with a better profile of MetS components, especially HDL-c.

Alcohol intake is associated with the risk of breast cancer. Different patterns of alcohol-drinking may have different effects on breast cancer even when keeping constant the total amount of alcohol consumed. We aimed to assess the association between binge drinking and breast cancer risk. The SUN Project is a Spanish dynamic prospective cohort of university graduates initiated in 1999. In the 556-item lifestyle baseline questionnaire a validated food-frequency questionnaire was embedded. Participants completed biennial follow-up questionnaires. Cox regression models were used to estimate the hazard ratio (HR) for breast cancer associated with the exposure to binge drinking. A stratified analysis was performed according to menopausal status. We included 9577 women (mean age = 34 years, SD = 10 years), with a median follow-up of 11.8 years. Among 104,932 women-years of follow-up, we confirmed 88 incident cases of breast cancer. Women in the binge drinking group showed a higher risk of breast cancer (HR = 1.76, 95% CI: 1.03&ndash, 2.99) compared to women in the non-binge drinking category. In the stratified analysis, a 2-fold higher risk for premenopausal breast cancer was associated with binge drinking habit (HR = 2.06, 95% CI: 1.11&ndash, 3.82). This study adds new evidence on the association of binge drinking with breast cancer risk.

Objectives Provegetarian diets, also known as predominantly plant-based (but not vegetarian or vegan) or plant-forward diets, have been associated with health benefits. However, a distinction is needed between high- and low-quality provegetarian dietary patterns (PVGs). We sought to examine potential associations between PVG indices and breast cancer (BC) incidence. Methods We assessed 10 812 women in the Seguimiento Universidad de Navarra cohort. We calculated an overall PVG pattern from a validated semi-quantitative food-frequency questionnaire as proposed by Martinez-Gonzalez et al, assigning positive scores (based on quintiles) to plant foods and reversing the quintile scores for animal foods. Participants were categorized according to tertiles of the overall score. We also calculated a healthful PVG (hPVG) and unhealthful PVG (uPVG) as proposed by Satija et al. Results After a median of 11.5 years of follow-up, 101 incident BC cases, confirmed by medical records, were observed. A significant inverse association with BC (comparing tertile 2 vs. tertile 1, HR= 0.55; 95% confidence interval, 0.32–0.95) was identified for a modest overall PVG, but not for hPVG and uPVG separately. Nevertheless, the highest tertile was not associated with BC. Conclusions In this large prospective cohort study, a moderate adherence to a PVG might decrease the risk of BC. Further studies should replicate and expand these results to other racial, ethnic, and socioeconomic groups.

OBJECTIVE: Due to the growing interest in the role of dietary patterns (DPs) on chronic diseases, we assessed the association between a posteriori identified DPs in the Seguimiento Universidad de Navarra (SUN) Project - a prospective cohort study in a Mediterranean country - and breast cancer (BC) risk. DESIGN: DPs were ascertained through a principal component analysis based on 31 predefined food groups. BC cases were initially identified through self-report or, if deceased, from death certificates or by notification by the next kin. Women reporting BC were asked to provide a copy of their medical report and diagnoses for confirmation purposes. We fitted Cox regression models to assess the association between adherence to the identified DPs and BC risk. SETTING: Spanish university graduates. PARTICIPANTS: We included 10 713 young and middle-aged - mainly premenopausal - women. RESULTS: After a median follow-up of 10·3 years, we identified 100 confirmed and 168 probable incident BC cases. We described two major DPs: 'Western dietary pattern' (WDP) and 'Mediterranean dietary pattern' (MDP). A higher adherence to a WDP was associated with an increased risk of overall BC (multivariable-adjusted HR for confirmed BC Q4 v. Q1 1·70; 95 % CI 0·93, 3·12; P for trend = 0·045). Contrarily, adherence to a MDP was inversely associated with premenopausal BC (multivariable-adjusted HR Q4 v. Q1 0·33; 95 % CI 0·12, 0·91). No significant associations were observed for postmenopausal BC. CONCLUSIONS: Whereas a higher adherence to the WDP may increase the risk of BC, a higher adherence to the MDP may decrease the risk of premenopausal BC. The study was supported by the “Acción Transversal del Cáncer", approved on the Spanish Ministry Council on the 11th October 2007, by the Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), by the Instituto de Salud Carlos III grants, cofunded by FEDER funds -a way to build Europe- PI08/1770 (to M. Kogevinas), PI09/0773 and FIS 12/00715 (to J. Llorca), PI09/1903 (to R. Peiró), PI09/2078 (to F.J. Caballero), PI09/1662 (to J.J. Jiménez- Moleón), PI11/01403 (to N. Aragonés), PI12/00150 (to B.Pérez- Gómez), PI12/00488 (to M.Pollán), by the Fundación Marqués de Valdecilla grant API 10/09 (to J. Llorca), by the Consejería de Salud of the Junta de Andalucía grant 2009-S0143 (to J. Alguacil), by the Conselleria de Sanitat of the Generalitat Valenciana grant AP061/10 (to R. Peiró), by the Regional Government of the Basque Country, by the Fundación Caja de Ahorros de Asturias, by the University of Oviedo and by the Spanish Ministry of Economyand Competitiveness Juan de la Cierva de Incorporación grant IJCI-2014-20900 (to A. Castelló). None of the funding institutions played any role in the present work. The content and views of this publication are those of the authors and do not necessarily reflect the official position of the Instituto de Salud Carlos III. Sí

Breast cancer (BC) incidence is increasing worldwide. Higher insulin resistance may potentially lead to an increased risk of BC. Sugar-sweetened beverages (SSB) are an acknowledged dietary factor that increases insulin resistance. However, the association between SSB and BC has not been widely explored. We evaluated the association between baseline consumption of SSB and the incidence of BC among relatively young women in a cohort of Spanish university graduates. We evaluated 10,713 middle-aged, Spanish female university graduates (median age 33) from the Seguimiento Universidad de Navarra (SUN) cohort, initially free of BC. SSB consumption was collected at baseline using a validated 136-item semi-quantitative food-frequency questionnaire. Incidence of BC was confirmed by a trained oncologist using medical records. We fitted Cox regression models to assess the relationship between baseline categories of SSB consumption and the incidence of BC during follow-up. We stratified the analyses by menopausal status. During 106,189 person-years follow-up, 100 incident cases of BC were confirmed. Among postmenopausal women, regular consumption of SSB was associated with a significantly higher incidence of BC (HR 2.12; 95% CI 1.02, 4.41) in the fully adjusted model, compared to women who never or seldom consumed SSB. No association was found among premenopausal women (HR 1.16; 95% CI 0.66, 2.07). Even though the number of cases was small, in this Mediterranean cohort, we observed a direct association between SSB consumption and BC risk among postmenopausal women. Nonetheless further larger longitudinal studies are needed to support this association.

Purpose: Plant-based diets have been associated with lower risk of various diseases, including type 2 diabetes, cardiovascular disease and other cardiometabolic risk factors and are recommended for both health and environmental benefits. However, the association between plant-based diet quality and breast cancer remains unclear. Therefore, we examined the associations of plant-based diet quality with risk of total and subtypes of breast cancer. Methods: We followed 74,516 women from the Nurses' Health Study (NHS, 1984-2016), and 93,915 women from the Nurses' Health Study II (NHSII, 1991-2017), without cancer at baseline. Incident invasive breast cancer cases were confirmed with medical records, and subtypes were determined by tissue microarray data and pathology reports. We assessed an overall plant-based diet index (PDI) from dietary data collected using repeated semi-quantitative food-frequency questionnaires (FFQ), by assigning positive scores to plant foods and reverse scores to animal foods. We also investigated a healthful PDI (hPDI) where healthy plant foods (whole grains, fruits/vegetables, nuts/legumes, oils, tea/coffee) received positive scores, while less healthy plant foods (juices/sweetened beverages, refined grains, potatoes/fries, sweets) and animal foods received reverse scores. We also assessed an unhealthful PDI (uPDI), assigning positive scores to less healthy plant foods, and reverse scores to healthy plant foods and animal foods. Multivariable hazard ratios (HRs) and 95% confidence intervals (CI) were calculated with Cox proportional hazards models using data pooled across cohorts, adjusting for breast cancer risk factors. Results: Over 4,193,915 person-years of follow-up, we documented 11,281 incident invasive breast cancer cases. Women with greater adherence to PDI were at modestly lower risk of breast cancer [HR Q5vsQ1 0.92; 95% CI 0.86, 0.99; p trend=0.02]. Furthermore, greater adherence to a hPDI was associated with a decreased risk of overall breast cancer [HR Q5vsQ1 0.90; 95% CI 0.85, 0.96, p trend= Conclusions: This study provides evidence that adherence to a plant-based dietary pattern and, specifically, its healthful version, may reduce the risk of breast cancer, especially those that are more likely to be aggressive tumors. In contrast, a low-quality plant-based diet may be associated with an increased risk of ER-negative breast cancer. Citation Format: Andrea Romanos-Nanclares, Walter C. Willett, Bernard Rosner, Laura C. Collins, Frank B. Hu, Estefania Toledo, A. Heather Eliassen. Healthful and unhealthful plant-based diets and risk of breast cancer in U.S. women: Results from the Nurses' Health Studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 837.

OBJECTIVES: Whether consumption of sugar-sweetened beverages (SSBs) or artificially sweetened beverages (ASBs) is associated with risk of breast cancer is of public health interest. Therefore, we aimed to evaluate associations between consumption of SSBs and ASBs with risk of total and subtype-specific breast cancer. METHODS: We followed 80,677 women from the Nurses’ Health Study (NHS; 1980 to 2016) and 86,115 women from the Nurses’ Health Study II (NHSII; 1991 to 2017) who were free from breast cancer at baseline. Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: We documented 10,248 breast cancer cases during 3,990,008 person-years of follow-up. Consumption of SSBs or ASBs were not associated with total breast cancer risk; pooled HR (95% CI) comparing extreme categories were 1.05 (0.97, 1.15) and 0.97 (0.91, 1.03), respectively. In cohort-specific analysis, SSBs were associated with a higher risk of breast cancer in NHS (HR (≥1/day vs.

There is growing interest in natural antioxidants and their potential effects on breast cancer (BC). Epidemiological evidence, however, is inconsistent. We prospectively evaluated the association between dietary intake of vitamins A, C, and E, selenium, and zinc and BC among 9983 female participants from the SUN Project, a Mediterranean cohort of university graduates. Participants completed a food frequency questionnaire at baseline, and biennial follow-up information about incident BC diagnosis was collected. Cases were ascertained through revision of medical charts and consultation of the National Death Index. Cox proportional hazards models were used to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CI). During an average follow-up of 11.3 years, 107 incident BC cases were confirmed. The multivariable HRs (95% CI) for BC comparing extreme tertiles of energy-adjusted dietary intakes were 1.07 (0.64–1.77, Ptrend = 0.673) for vitamin A, 1.00 (0.58–1.71, Ptrend = 0.846) for vitamin C, 0.92 (0.55–1.54, Ptrend = 0.728) for vitamin E, 1.37 (0.85–2.20, Ptrend = 0.135) for selenium, and 1.01 (0.61–1.69, Ptrend = 0.939) for zinc. Stratified analyses showed an inverse association between vitamin E intake and postmenopausal BC (HRT3 vs. T1 = 0.35, 95% CI, 0.14–0.86, Ptrend = 0.027). Our results did not suggest significant protective associations between dietary vitamins A, C, and E, selenium, or zinc and BC risk.

A proportion of breast cancer cases are attributable to combined modifiable risk factors. The World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) has recently updated the recommendations for cancer prevention and a standard scoring system has been published. The aim of this study was to evaluate the association between compliance with the 2018 WCRF/AICR cancer prevention recommendations (Third Expert Report) and the risk of breast cancer in the SUN (&ldquo, Seguimiento Universidad de Navarra&rdquo, ) prospective cohort. Spanish female university graduates, initially free of breast cancer, were included (n = 10,930). An 8-item score to measure compliance to the recommendations was built: body fat, physical activity, consumption of wholegrains/vegetables/fruit/beans, &ldquo, fast foods&rdquo, red/processed meat consumption, sugar-sweetened drinks consumption, alcohol intake, and breastfeeding. A stratified analysis was conducted according to menopausal status. A non-significant inverse association was observed for overall breast cancer. The inverse association became statistically significant for post-menopausal breast cancer after multivariable adjustment (hazard ratio for &gt, 5 vs. &le, 3 points = 0.27, 95% CI: 0.08-0.93). The results suggested that the possible inverse association with breast cancer was attributable to the combined effects of the different nutritional and lifestyle components.

Summary Background & aims Breast cancer (BC) is the most commonly diagnosed cancer, and diet is suspected to play a role in its development. Dietary factors may mediate this process through modulation of inflammation, though findings from previous studies have not been consistent. We aimed to longitudinally assess the association between the dietary inflammatory index (DII®), a frequently used method to assess the inflammatory potential of the diet, and incident BC. Methods We included 10,713 middle-aged, Spanish female university graduates from the SUN cohort. DII® scores were derived from a validated 136-item food-frequency questionnaire, and it was based on scientific evidence on the relationship between diet and inflammatory biomarkers. Diagnosis of BC was reported by the participant or, if deceased, by the next of kin or identified from death certificates. Self-reports of BC were confirmed by revision of medical reports by an experienced oncologist. Cox proportional hazard models were used to estimate multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) for the association between quartiles of DII® and incident BC. Results After 10.3 years of median follow-up, we identified 100 confirmed and 168 probable incident BC cases. The multivariable-adjusted HR for participants in the 4th quartile to the 1st quartile was 1.44 (95% CI 0.76–2.72; p-trend: 0.339) when confirmed cases were analyzed, and 1.20 (95% CI 0.72–1.99; p-trend: 0.757) for the probable cases. We neither observed statistically significant differences in regard to menopausal status. Conclusions The apparent increase in risk between DII® scores and BC in our cohort was not statistically significant, which could be partly explained by the small number of observed cases.