Associations of low-carbohydrate diets with breast cancer survival.

BACKGROUND: The objective of this study was to evaluate the role of low-carbohydrate diets after breast cancer diagnosis in relation to breast cancer-specific and all-cause mortality. METHODS: For 9621 women with stage I-III breast cancer from two ongoing cohort studies, the Nurses' Health Study and Nurses' Health Study II, overall low-carbohydrate, animal-rich low-carbohydrate, and plant-rich low-carbohydrate diet scores were calculated by using food frequency questionnaires collected after breast cancer diagnosis. RESULTS: Participants were followed up for a median 12.4 years after breast cancer diagnosis. We documented 1269 deaths due to breast cancer and 3850 all-cause deaths. With the use of Cox proportional hazards regression and after controlling for potential confounding variables, we observed a significantly lower risk of overall mortality among women with breast cancer who had greater adherence to overall low-carbohydrate diets (hazard ratio for quintile 5 vs. quintile 1 [HRQ5vsQ1 ], 0.82; 95% CI, 0.74-0.91; ptrend  = .0001) and plant-rich low-carbohydrate diets (HRQ5vsQ1 , 0.73; 95% CI, 0.66-0.82; ptrend < .0001) after breast cancer diagnosis but not animal-rich low-carbohydrate diets (HRQ5vsQ1 , 0.93; 95% CI, 0.84-1.04; ptrend  = .23). However, greater adherence to overall, animal-rich, or plant-rich low-carbohydrate diets was not significantly associated with a lower risk of breast cancer-specific mortality. CONCLUSIONS: This study showed that greater adherence to low-carbohydrate diets, especially plant-rich low-carbohydrate diets, was associated with better overall survival but not breast cancer-specific survival among women with stage I-III breast cancer.

Physical activity and breast cancer survival: results from the Nurses' Health Studies.

BACKGROUND: Physical activity is generally associated with better outcomes following diagnosis; however, few studies have evaluated change in pre- to postdiagnosis activity and repeated measures of activity by intensity and type. METHODS: We evaluated physical activity and survival following a breast cancer diagnosis in the Nurses' Health Study and Nurses' Health Study II (n = 9308 women, n = 1973 deaths). Physical activity was evaluated as updated cumulative average of metabolic equivalent of task (MET)-h/wk (assigned per activity based on duration and intensity) and change in pre- to postdiagnosis activity. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Higher postdiagnosis activity was inversely associated with breast cancer-specific mortality in categories from ≥9 MET-h/wk (vs <3 MET h/wk, HR≥9 to <18 = 0.74 [95% CI = 0.55 to 0.99]; HR≥27 = 0.69 [95% CI = 0.50 to 0.95]; Ptrend = .04) and all-cause mortality from ≥3 MET-h/wk (HR≥3 to <9 = 0.73 [95% CI = 0.61 to 0.88]; HR≥27 = 0.51 [95% CI = 0.41 to 0.63]; Ptrend < .001). Associations were predominantly observed for estrogen receptor-positive tumors and in postmenopausal women. Walking was associated with lower risk of all-cause mortality (≥9 vs <3 MET-h/wk, HR= 0.69 [95% CI = 0.57 to 0.84]) as was strength training. Relative to stable activity pre- to postdiagnosis (±3 MET-h/wk), increases from ≥3 to 9 MET-h/wk were associated with lower all-cause mortality risk (Ptrend < .001). Results were robust to adjustment for prediagnosis physical activity. CONCLUSIONS: Physical activity was associated with lower risk of death following diagnosis. Increased pre- to postdiagnosis activity corresponding to at least 1-3 h/wk of walking was associated with lower risk of death. These results provide further impetus for women to increase their activity after a breast cancer diagnosis, though reverse causation cannot be fully excluded.

Dietary and Supplemental Vitamin C Intake and Risk of Breast Cancer: Results from the Nurses' Health Studies.

BACKGROUND: Some previous studies suggested that high supplemental vitamin C intake may be associated with an increased risk of breast cancer, although evidence is inconsistent. OBJECTIVES: Our objective was to study the association between vitamin C intake and breast cancer risks using regularly updated assessments of intake over a long follow-up. METHODS: We prospectively followed 88,041 women aged 33 to 60 years from the Nurses' Health Study (1980-2014) and 93,372 women aged 26 to 45 years from the Nurses' Health Study II (1991-2013). A total of 11,258 incident invasive breast cancers among 181,413 women were diagnosed. Data on vitamin C intake were collected every 2-4 years via a validated FFQ and specific questions on dietary supplement use. Multivariate HRs and 95% CIs for incident invasive breast cancer were estimated with Cox models. RESULTS: During follow-up, 82% of participants ever used supplements containing vitamin C, including multivitamins. Cumulative total vitamin C intake (HR for quintiles 5 compared with 1 = 0.97; 95% CI: 0.91-1.03; Ptrend = 0.81), dietary vitamin C intake (HR for quintiles 5 compared with 1 = 0.98; 95% CI: 0.92-1.04; Ptrend = 0.57), and supplemental vitamin C intake (HR for quintiles 5 compared with 1 in users = 1.02; 95% CI: 0.94-1.09; Ptrend = 0.77) were not associated with breast cancer risks. Results were unchanged when different exposure latencies were considered. The results did not differ by menopausal status, postmenopausal hormone therapy use, or BMI. No differences were observed by estrogen receptor status of the tumor. CONCLUSIONS: Our results do not support any important association between total, dietary, or supplemental vitamin C intake and breast cancer risks.

The Association of Religion and Spirituality with Obesity and Weight Change in the USA: A Large-Scale Cohort Study.

The association between religion, spirituality, and body weight is controversial, given the methodological limitations of existing studies. Using the Nurses' Health Study II cohort, follow-up occurred from 2001 to 2015, with up to 35,547 participants assessed for the religious or spiritual coping and religious service attendance analyses. Cox regression and generalized estimating equations evaluated associations with obesity and weight change, respectively. Religious or spiritual coping and religious service attendance had little evidence of an association with obesity. Compared with not using religious or spiritual coping at all, the fully adjusted hazard ratios (HRs) were minimally different across categories: a little bit (HR = 1.05, 95% CI: 0.92-1.18), a medium amount (HR = 1.09, 95% CI: 0.96-1.24), and a lot (HR = 1.10; 95% CI: 0.96-1.25) (Ptrend = 0.17). Compared with participants who never or almost never attend religious meetings or services, there was little evidence of an association between those attending less than once/month (HR = 1.08, 95% CI: 0.97-1.10), 1-3 times/month (HR = 1.01, 95% CI: 0.90-1.13), once/week (HR = 0.92, 95% CI: 0.83-1.02), and more than once/week (HR = 0.94, 95% CI: 0.82-1.07) (Ptrend = 0.06). Findings were similar for weight change. There was no significant association between religious or spiritual coping, religious service attendance, obesity, and weight change. While religion and spirituality are prominent in American society, they are not important psychosocial factors influencing body weight in this sample.

Religious or spiritual coping, religious service attendance, and type 2 diabetes: A prospective study of women in the United States.

PURPOSE: To investigate religion and spirituality (R/S) as psychosocial factors in type 2 diabetes risk. METHODS: Using the Nurses' Health Study II, we conducted a 14-year prospective analysis of 46,713 women with self-reported use of religion or spiritual beliefs to cope with stressful situations, and 42,825 women with self-reported religious service attendance, with respect to type 2 diabetes. Cox regression was used to assess the associations. RESULTS: Compared with not using religious or spiritual coping at all, the fully-adjusted hazard ratios (HR) were minimally different across all categories: a little bit (HR=1.01; 95% CI:0.85, 1.19), a medium amount (HR=0.96; 95% CI:0.80, 1.14), a lot (HR=0.93; 95% CI: 0.77, 1.11) (Ptrend=0.24). Similarly, compared with participants who never or almost never attend religious meetings or services, there were minimal differences with participants attending less than once/month (HR=1.06; 95% CI:0.92, 1.22), 1-3 times/month (HR=1.00; 95% CI:0.85, 1.17), once/week (HR=0.98; 95% CI:0.85, 1.14), more than once/week (HR=1.20; 95% CI:1.01, 1.43) (Ptrend=0.29). Perceived stress did not modify these associations. Our hypothesis of mediated effects through lifestyle factors and social integration was not supported. CONCLUSIONS: R/S was not significantly associated with type 2 diabetes, but its role in other chronic conditions may be important.

Consumption of red meat and processed meat and cancer incidence: a systematic review and meta-analysis of prospective studies.

Red meat and processed meat consumption has been hypothesized to increase risk of cancer, but the evidence is inconsistent. We performed a systematic review and meta-analysis of prospective studies to summarize the evidence of associations between consumption of red meat (unprocessed), processed meat, and total red and processed meat with the incidence of various cancer types. We searched in MEDLINE and EMBASE databases through December 2020. Using a random-effect meta-analysis, we calculated the pooled relative risk (RR) and 95% confidence intervals (CI) of the highest versus the lowest category of red meat, processed meat, and total red and processed meat consumption in relation to incidence of various cancers. We identified 148 published articles. Red meat consumption was significantly associated with greater risk of breast cancer (RR = 1.09; 95% CI = 1.03-1.15), endometrial cancer (RR = 1.25; 95% CI = 1.01-1.56), colorectal cancer (RR = 1.10; 95% CI = 1.03-1.17), colon cancer (RR = 1.17; 95% CI = 1.09-1.25), rectal cancer (RR = 1.22; 95% CI = 1.01-1.46), lung cancer (RR = 1.26; 95% CI = 1.09-1.44), and hepatocellular carcinoma (RR = 1.22; 95% CI = 1.01-1.46). Processed meat consumption was significantly associated with a 6% greater breast cancer risk, an 18% greater colorectal cancer risk, a 21% greater colon cancer risk, a 22% greater rectal cancer risk, and a 12% greater lung cancer risk. Total red and processed meat consumption was significantly associated with greater risk of colorectal cancer (RR = 1.17; 95% CI = 1.08-1.26), colon cancer (RR = 1.21; 95% CI = 1.09-1.34), rectal cancer (RR = 1.26; 95% CI = 1.09-1.45), lung cancer (RR = 1.20; 95% CI = 1.09-1.33), and renal cell cancer (RR = 1.19; 95% CI = 1.04-1.37). This comprehensive systematic review and meta-analysis study showed that high red meat intake was positively associated with risk of breast cancer, endometrial cancer, colorectal cancer, colon cancer, rectal cancer, lung cancer, and hepatocellular carcinoma, and high processed meat intake was positively associated with risk of breast, colorectal, colon, rectal, and lung cancers. Higher risk of colorectal, colon, rectal, lung, and renal cell cancers were also observed with high total red and processed meat consumption.

Types of carbohydrate intake and breast cancer survival.

OBJECTIVE: To investigate the associations of different types of carbohydrate intake after breast cancer diagnosis with breast cancer-specific and all-cause mortality. METHODS: We prospectively assessed post-diagnostic intake of total sugar, added sugar, and natural sugar as well as carbohydrate from different sources, among 8932 women with stage I-III breast cancer that were identified in the Nurses' Health Study from 1980 to 2010 and Nurses' Health Study II from 1991 to 2011. Participants completed a validated food frequency questionnaire every four years after diagnosis and were followed up for death. RESULTS: We prospectively documented 1071 deaths due to breast cancer and 2532 all-cause deaths, over a mean of 11.5 years of follow-up. After adjustment for confounding variables, greater post-diagnostic total sugar intake was suggestively associated with greater risk of breast cancer-specific mortality [hazard ratio (HR)Q5vsQ1 = 1.16, 95% confidence interval (CI ) = 0.95-1.41; Ptrend = 0.02] and significantly associated with greater risk of all-cause mortality (HRQ5vsQ1 = 1.23, 95% CI = 1.08-1.41; Ptrend = 0.0001). Greater post-diagnostic added sugar intake was significantly associated with greater risk of all-cause mortality (HRQ5vsQ1 = 1.20, 95% CI = 1.06-1.36; Ptrend = 0.001). Post-diagnostic natural sugar (occurring in foods and not added as an ingredient) intake was not associated with mortality risk. Greater post-diagnostic fructose intake was significantly associated with greater risk of breast cancer-specific mortality (HRQ5vsQ1 = 1.34, 95% CI = 1.10-1.64; Ptrend = 0.005) and all-cause mortality (HRQ5vsQ1 = 1.16, 95% CI = 1.02-1.32; Ptrend = 0.01). High post-diagnostic intake of sucrose was associated with higher risk of breast cancer-specific and all-cause mortality. Increased post-diagnostic intake of carbohydrate from fruit juice was significantly associated with higher risk of breast cancer-specific and all-cause mortality and carbohydrate from vegetables was significantly associated with lower risk of all-cause mortality. High post-diagnostic intake of carbohydrate from potatoes was suggestively associated with higher risk of breast cancer-specific mortality and carbohydrate from refined grains was suggestively associated with higher risk of all-cause mortality. CONCLUSIONS: We found that higher total sugar intake, especially added sugar, sucrose, and fructose, as well as carbohydrate from fruit juice after a breast cancer diagnosis were associated with poorer prognosis. High post-diagnostic intake of carbohydrate from vegetables was associated with reduced risk of mortality.

Diabetes Risk Reduction Diet and Survival after Breast Cancer Diagnosis.

Type II diabetes is associated with poor breast cancer prognosis. To study the association between a diabetes risk reduction diet (DRRD) and survival following breast cancer, we followed 8,482 women with breast cancer from two large cohort studies. Information on diet and other factors was repeatedly measured in validated questionnaires every two to four years. The DRRD includes 9 components: higher intakes of cereal fiber, coffee, nuts, whole fruits and polyunsaturated/saturated fat ratio; and lower glycemic index, trans fat, sugar-sweetened beverages, and red meat. Cumulative average DRRD score was calculated using repeated measures of postdiagnostic diet. Deaths were assessed by family members or via National Death Index. Multivariable-adjusted HRs and 95% confidence intervals (CI) were estimated using Cox proportional hazards models. During a median of 14 years of follow-up since diagnosis, 2,600 deaths occurred among participants, 1,042 of which were due to breast cancer. Women with higher postdiagnostic DRRD score had a 20% lower risk of breast cancer-specific mortality (top vs. bottom quintile HR = 0.80; 95% CI = 0.65-0.97; P trend = 0.02) and 34% lower risk of all-cause mortality (HR = 0.66; 95% CI = 0.58-0.76; P trend < 0.0001). Compared with women who consistently had lower score (≤median) before and after diagnosis, those whose score improved from low to high had a lower risk of breast cancer-specific mortality (HR = 0.77; 95% CI = 0.62-0.95) and overall mortality (HR = 0.85; 95% CI = 0.74-0.97). These findings demonstrate that greater adherence to DRRD was associated with better survival, suggesting postdiagnosis dietary modification consistent with type II diabetes prevention may be important for breast cancer survivors. SIGNIFICANCE: This study suggests that greater adherence to the diabetes risk reduction diet after diagnosis associates with improved survival outcomes among a large number of breast cancer survivors.

Fruit and vegetable consumption and incident breast cancer: a systematic review and meta-analysis of prospective studies.

BACKGROUND: We conducted a systematic review and meta-analysis of prospective studies to clarify the relation of fruit and vegetable consumption with incident breast cancer. METHODS: We searched systematically PubMed and EMBASE databases up to November 2020 to include prospective studies that reported the association of fruit and vegetable consumption with incident breast cancer. The pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated for the highest versus the lowest category of total fruit and vegetable, total fruit and total vegetable consumption, as well as fruit juice and subgroups of vegetables in relation to breast cancer incidence, using a random-effect model. RESULTS: Total fruit and vegetable consumption was associated with lower overall (RR = 0.91, 95% CI = 0.87-0.95) and postmenopausal breast cancer risk (RR = 0.88, 95% CI = 0.79-0.99). Total fruit consumption was associated with lower overall (RR = 0.93, 95% CI = 0.88-0.99) and postmenopausal breast cancer risk (RR = 0.93, 95% CI = 0.87-0.99). Total fruit and vegetable intake were associated with 11% and 26% lower risk of oestrogen- and progesterone-receptor-positive (ER+/PR+) and -negative (ER-/PR-) breast cancer, respectively. Total vegetable consumption was associated with 27% lower risk of ER-/PR- breast cancer. Fruit juice consumption was associated with increased overall breast cancer risk (RR = 1.04, 95% CI = 1.01-1.07). We did not find significant associations for subgroups of vegetable intake and breast cancer risk. CONCLUSIONS: These findings suggest that high total fruit and vegetable consumption are associated with reduced risk of overall, postmenopausal, ER+/PR+ and ER-/PR- breast cancer.

Consumption of sugar-sweetened and artificially sweetened beverages and breast cancer survival.

BACKGROUND: The activation of insulin pathways is hypothesized to promote tumor growth and worsen breast cancer survival. Sugar-sweetened beverages (SSBs) can lead to a higher risk of insulin resistance and may affect survival. The authors prospectively evaluated the relation of postdiagnostic SSB and artificially sweetened beverage (ASB) consumption with mortality among women with breast cancer. METHODS: In total, 8863 women with stage I through III breast cancer were identified during follow-up of the Nurses' Health Study (NHS; 1980-2010) and Nurses' Health Study II (NHSII; 1991-2011). Women completed a validated food frequency questionnaire every 4 years after diagnosis and were followed until death or the end of follow-up (2014 for the NHS and 2015 for the NHSII). Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of breast cancer-specific and all-cause mortality after adjusting for measures of adiposity and other potential predictors of cancer survival. RESULTS: With a median follow-up of 11.5 years, 2482 deaths were prospectively documented, including 1050 deaths from breast cancer. Compared with women who had no consumption, women who had SSB consumption after diagnosis had higher breast cancer-specific mortality (>1 to 3 servings per week: HR, 1.31 [95% CI, 1.09-1.58]; >3 servings per week: HR, 1.35 [95% CI, 1.12-1.62]; Ptrend = .001) and all-cause mortality (>1 to 3 servings per week: HR, 1.21 [95% CI, 1.07-1.37]; >3 servings per week: HR, 1.28 [95% CI, 1.13-1.45]; Ptrend = .0001). In contrast, ASB consumption was not associated with higher breast cancer-specific or all-cause mortality. Furthermore, replacing 1 serving per day of SSB consumption with 1 serving per day of ASB consumption was not associated with a lower risk of mortality. CONCLUSIONS: Higher postdiagnostic SSB consumption among breast cancer survivors was associated with higher breast cancer-specific mortality and death from all causes.

Post-diagnostic coffee and tea consumption and breast cancer survival.

BACKGROUND: We examined the role of post-diagnostic coffee and tea consumption in relation to breast cancer-specific and all-cause mortality among women with breast cancer in prospective cohort studies. METHODS: We identified 8900 women with stage I-III breast cancer from 1980 through 2010 in the Nurses' Health Study (NHS) and from 1991 through 2011 in the NHSII. Post-diagnostic coffee and tea consumption was assessed by a validated food frequency questionnaire every 4 years after diagnosis. RESULTS: During up to 30 years of follow-up, we documented 1054 breast cancer-specific deaths and 2501 total deaths. Higher post-diagnostic coffee consumption was associated with a lower breast cancer-specific mortality: compared with non-drinkers, >3 cups/day of coffee was associated with a 25% lower risk (hazard ratio (HR) = 0.75, 95% confidence interval (CI) = 0.59-0.96; Ptrend = 0.002). We also observed a lower all-cause mortality with coffee consumption: compared with non-drinkers, >2 to 3 cups/day was associated with a 24% lower risk (HR = 0.76, 95% CI = 0.66-0.87) and >3 cups/day was associated with a 26% lower risk (HR = 0.74, 95% CI = 0.63-0.87, Ptrend < 0.0001). Post-diagnostic tea consumption was associated with a lower all-cause mortality: compared with non-drinkers, >3 cups/day was associated with a 26% lower risk (HR = 0.74, 95% CI = 0.58-0.95; Ptrend = 0.04). CONCLUSIONS: Among breast cancer survivors, higher post-diagnostic coffee consumption was associated with better breast cancer and overall survival. Higher post-diagnostic tea consumption may be related to better overall survival.

Dairy intake during adolescence and risk of colorectal adenoma later in life.

BACKGROUND: Higher dairy intake during adulthood has been associated with lower colorectal cancer risk. As colorectal carcinogenesis spans several decades, we hypothesised that higher dairy intake during adolescence is associated with lower risk of colorectal adenoma, a colorectal cancer precursor. METHODS: In 27,196 females from the Nurses' Health Study 2, aged 25-42 years at recruitment (1989), who had completed a validated high school diet questionnaire in 1998 and undergone at least one lower bowel endoscopy between 1998 and 2011, logistic regression for clustered data was used to calculate odds ratios (ORs) and 95% confidence intervals (CI). RESULTS: Colorectal adenomas were diagnosed in 2239 women. Dairy consumption during adolescence was not associated with colorectal adenoma risk (OR highest vs. lowest [≥4 vs. ≤1.42 servings/day] quintile [95% CI] 0.94 [0.80, 1.11]). By anatomical site, higher adolescent dairy intake was associated with lower rectal (0.63 [0.42, 0.95]), but not proximal (1.01 [0.80, 1.28]) or distal (0.97 [0.76, 1.24]) colon adenoma risk. An inverse association was observed with histologically advanced (0.72 [0.51, 1.00]) but not non-advanced (1.07 [0.86, 1.33]) adenoma. CONCLUSIONS: In this large cohort of younger women, higher adolescent dairy intake was associated with lower rectal and advanced adenoma risk later in life.

Postdiagnostic Dietary Glycemic Index, Glycemic Load, Dietary Insulin Index, and Insulin Load and Breast Cancer Survival.

BACKGROUND: We investigated the associations of postdiagnostic dietary glycemic index (GI), glycemic load (GL), insulin index (II), and insulin load (IL) with breast cancer-specific and all-cause mortality. METHODS: Among 8,932 women with stage I-III breast cancer identified in the Nurses' Health Study (NHS; 1980-2010) and NHSII (1991-2011), we prospectively evaluated the associations between postdiagnostic GI, GL, II, and IL, and breast cancer-specific and all-cause mortality. Participants completed a validated food frequency questionnaire every 4 years after diagnosis. RESULTS: During follow-up by 2014 in the NHS and 2015 in the NHSII, 2,523 deaths, including 1,071 from breast cancer, were documented. Higher postdiagnostic GL was associated with higher risk of both breast cancer-specific mortality [HRQ5vsQ1 = 1.33; 95% confidence interval (CI) = 1.09-1.63; P trend = 0.008] and all-cause mortality (HRQ5vsQ1 = 1.26; 95% CI = 1.10-1.45; P trend = 0.0006). Higher all-cause mortality was also observed with higher postdiagnostic GI (HRQ5vsQ1 = 1.23; 95% CI = 1.08-1.40; P trend = 0.001), II (HRQ5vsQ1 = 1.20; 95% CI = 1.04-1.38; P trend = 0.005), and IL (HRQ5vsQ1 = 1.23; 95% CI = 1.07-1.42; P trend = 0.0003). The associations were not modified by insulin receptor or estrogen receptor status of the tumor, or body mass index. CONCLUSIONS: We found that higher dietary GL, reflecting postprandial glucose response, after a breast cancer diagnosis was associated with higher risk of breast cancer-specific mortality. Higher dietary GI, GL, II, and IL after a breast cancer diagnosis were associated with higher risk of death from any cause. IMPACT: These results suggest that carbohydrate quantity and quality may be important in breast cancer prognosis.See related commentary by McTiernan, p. 252.

Postdiagnostic Fruit and Vegetable Consumption and Breast Cancer Survival: Prospective Analyses in the Nurses' Health Studies.

Fruits and vegetables contain many bioactive components that may contribute to improved survival after diagnosis of breast cancer, however, evidence to date is insufficient. We prospectively assessed the associations of postdiagnostic fruit and vegetable consumption with breast cancer-specific and all-cause mortality among 8,927 women with stage I-III breast cancer identified during follow-up of the Nurses' Health Study (NHS; 1980-2010) and NHSII (1991-2011), using a validated food frequency questionnaire completed every 4 years after diagnosis. We prospectively documented 2,521 deaths, including 1,070 from breast cancer through follow-up until 2014 in the NHS and 2015 in the NHSII. Total fruit and vegetable and total vegetable consumption was related to lower all-cause [HRQ5vsQ1, 0.82; 95% confidence interval (CI), 0.71-0.94; P trend = 0.004, and HRQ5vsQ1, 0.84; 95% CI, 0.72-0.97; P trend = 0.001, respectively], but not breast cancer-specific mortality. Total fruit consumption was not related to breast cancer-specific or all-cause mortality. Greater intake of green leafy and cruciferous vegetables was associated with lower all-cause mortality. Each 2 servings/week of blueberries was associated with a 25% (HR, 0.75; 95% CI, 0.60-0.94) lower breast cancer-specific and a 17% (HR, 0.83; 95% CI, 0.72-0.96) lower all-cause mortality. In contrast, higher fruit juice consumption was associated with higher breast cancer-specific (HRQ5vsQ1, 1.33; 95% CI, 1.09-1.63; P trend = 0.002) and all-cause mortality (HRQ5vsQ1, 1.19; 95% CI, 1.04-1.36; P trend = 0.003). Apple juice largely accounted for these higher risks and orange juice was not associated with risk. Higher postdiagnostic fruit and vegetable consumption among breast cancer survivors was not associated with breast cancer-specific mortality. However, our findings suggest that higher vegetable consumption, particularly green leafy and cruciferous vegetables, was associated with better overall survival among patients with breast cancer. Higher fruit juice consumption, but not orange juice, was associated with poorer breast cancer-specific and all-cause survival. SIGNIFICANCE: A large-scale study shows that high fruit and vegetable consumption may be associated with better overall survival among breast cancer patients, while high fruit juice consumption may be associated with poorer porgnosis.

Prospective study of a diabetes risk reduction diet and the risk of breast cancer.

BACKGROUND: Hyperinsulinemia and higher insulin-like growth factors may increase breast cancer risk. We evaluated a diabetes risk reduction diet (DRRD) and breast cancer risk. OBJECTIVES: We prospectively evaluated the association between adherence to a DRRD and the incidence of breast cancer. METHODS: We followed 88,739 women from the Nurses' Health Study (NHS; 1980-2016) and 93,915 women from the NHSII (1991-2017). Incident breast cancer cases (n = 11,943) were confirmed with medical records, and subtypes were determined by tissue microarray data and pathology reports. Information on diet and breast cancer risk factors was repeatedly ascertained in follow-up questionnaires. A DRRD score was derived with 9 factors: lower glycemic index of diet; lower intakes of trans fat, sugar-sweetened beverages/fruit juices, and red/processed meat; higher intakes of cereal fiber, coffee, nuts, and whole fruits; and a higher ratio of polyunsaturated to saturated fat (score range: 9-45). Multivariable-adjusted hazard ratios (MVHRs) and 95% CIs were calculated with Cox proportional hazards models. RESULTS: Being in the highest compared with the lowest DRRD adherence quintile was associated with a modestly lower breast cancer risk (MVHRQ5vsQ1: 0.89; 95% CI: 0.84, 0.95; P-trend = 0.0002); this was attenuated after adjusting for weight change since age 18 y (MVHRQ5vsQ1: 0.92; 95% CI: 0.87, 0.98; P-trend = 0.01). The inverse association was strongest among women with current BMI < 25 kg/m2 (MVHRQ5vsQ1: 0.89; 95% CI: 0.81, 0.98; P-trend = 0.004; P-interaction = 0.04). Among tumor molecular subtypes, the strongest inverse association was observed with basal-type tumors (MVHRQ5vsQ1: 0.67; 95% CI: 0.45, 1.01; P-trend = 0.04). CONCLUSIONS: Greater DRRD-adherence was associated with lower breast cancer risk, likely mediated by less weight gain with a DRRD; however, independently of weight change, DRRD-adherence was modestly associated with lower breast cancer risk, particularly among lean women.

Erythrocyte membrane fatty acids and breast cancer risk by tumor tissue expression of immuno-inflammatory markers and fatty acid synthase: a nested case-control study.

BACKGROUND: Previous studies of fatty acids and breast cancer risk have shown mixed results, which may be due in part to tumor heterogeneity. Prior research has also illustrated an important role of specific fatty acids in immune regulation, T cell function, and inflammation, indicating that the effects of specific fatty acids on breast cancer risk may vary by tumor expression of immuno-inflammatory markers. We therefore aimed to evaluate the relationships between prediagnostic erythrocyte membrane fatty acids and breast cancer risk by tumor tissue expression of immuno-inflammatory markers (CD4, CD8, CD20, CD163, COX-2) and fatty acid synthase (FAS). METHODS: We conducted a matched case-control study nested within the Nurses' Health Study II (n = 235 cases and 235 controls). Blood samples were collected from 1996 to 1999. Tumor tissue blocks were collected for cases diagnosed after blood collection and through 2006. Unconditional nominal polytomous logistic regression adjusted for matching factors and potential confounders was used to assess whether associations between fatty acids and breast cancer risk varied by tumor expression subtype, ascertained via immunohistochemistry. Odds ratios (OR) and 95% confidence intervals (CI) were estimated separately by tumor expression subtype using unconditional logistic regression. RESULTS: Associations between fatty acids and breast cancer risk did not vary substantially by tumor CD4, CD20, CD163, or COX-2. However, n-3 polyunsaturated fatty acids (PUFAs) were inversely associated with CD8low but not CD8high cancers (CD8low ORT3 vs T1 = 0.45, 95% CI 0.23-0.87, Ptrend = 0.02; CD8high ORT3 vs T1 = 1.19, 95% CI 0.62-2.26, Ptrend = 0.62; Phet = 0.04). n-6 PUFAs were suggestively inversely associated with CD8high but not CD8low cancers (CD8high ORT3 vs T1 = 0.61, 95% CI 0.32-1.14, Ptrend = 0.11; CD8low ORT3 vs T1 = 1.63, 95% CI 0.87-3.04, Ptrend = 0.12; Phet = 0.02). Trans fatty acids were positively associated with FAShigh but not FASlow tumors (FAShigh ORT3 vs T1 = 2.94, 95% CI 1.46-5.91, Ptrend = 0.002; FASlow ORT3 vs T1 = 0.99, 95% CI 0.52-1.92, Ptrend = 0.97; Phet = 0.01). CONCLUSION: Results indicate that the effects of n-3 PUFAs, n-6 PUFAs, and trans fatty acids on breast cancer risk may vary by tumor tissue expression subtypes. Findings suggest potential immuno-modulatory and FAS-mediated mechanisms.

Fiber consumption and breast cancer incidence: A systematic review and meta-analysis of prospective studies.

BACKGROUND: Associations between fiber intake and breast cancer risk have been evaluated in prospective studies, but overall, the evidence is inconsistent. The authors performed a systematic review and meta-analysis of prospective studies to investigate the relation between intake of total and types of fiber with breast cancer incidence. METHODS: The MEDLINE and Excerpta Medica dataBASE (EMBASE) databases were searched through July 2019 for prospective studies that reported on the association between fiber consumption and incident breast cancer. The pooled relative risk (RR) and 95% confidence intervals (95% CI) were estimated comparing the highest versus the lowest category of total and types of fiber consumption, using a random-effects meta-analysis. RESULTS: The authors identified 17 cohort studies, 2 nested case-control studies, and 1 clinical trial study. Total fiber consumption was associated with an 8% lower risk of breast cancer (comparing the highest versus the lowest category, pooled RR, 0.92; 95% CI, 0.88-0.95 [I2  = 12.6%]). Soluble fiber was found to be significantly inversely associated with risk of breast cancer (pooled RR, 0.90 [95% CI, 0.84-0.96; I2 = 12.6%]) and insoluble fiber was found to be suggestively inversely associated with risk of breast cancer (pooled RR, 0.93 [95% CI, 0.86-1.00; I2 = 33.4%]). Higher total fiber intake was associated with a lower risk of both premenopausal and postmenopausal breast cancers (pooled RR, 0.82 [95% CI, 0.67-0.99; I2  = 35.2%] and pooled RR, 0.91 [95% CI, 0.88-0.95; I2  = 0.0%], respectively). Furthermore, the authors observed a nonsignificant inverse association between intake of total fiber and risk of both estrogen and progesterone receptor-positive and estrogen and progesterone receptor-negative breast cancers. CONCLUSIONS: A random-effects meta-analysis of prospective observational studies demonstrated that high total fiber consumption was associated with a reduced risk of breast cancer. This finding was consistent for soluble fiber as well as for women with premenopausal and postmenopausal breast cancer.

Religious Service Attendance, Religious Coping, and Risk of Hypertension in Women Participating in the Nurses' Health Study II.

The association between religious service attendance, religious coping, and hypertension is unclear. Prospective research and assessment of potential mediators is needed to understand this relationship. From 2001-2013, we prospectively followed 44,281 nonhypertensive women who provided information on religious service attendance and religious coping in the Nurses' Health Study II. Cox regression and mediation analyses were conducted to assess associations between religion and hypertension. There were 453,706 person-years of follow-up and 11,773 incident hypertension cases. Women who attended religious services were less likely to develop hypertension. In the fully adjusting model, compared with women who never or almost never attend religious meetings or services, women attending less than once per month (hazard ratio (HR) = 0.97, 95% confidence interval (CI): 0.91, 1.03), 1-3 times per month (HR = 0.94, 95% CI: 0.88, 1.00), once per week (HR = 0.93, 95% CI: 0.88, 0.98), or more than once per week (HR = 0.91, 95% CI: 0.86, 0.97) showed a decreased risk of hypertension (P for trend = 0.001). Body mass index was an important mediator (11.5%; P < 0.001). Religious coping had a marginal association with hypertension. In conclusion, religious service attendance was modestly associated with hypertension in an inverse dose-response manner and partially mediated through body mass index. Future research is needed on biological or social reasons for the lower risk of hypertension.

The application of six dietary scores to a Middle Eastern population: a comparative analysis of mortality in a prospective study.

Background The associations between dietary indices and mortality have not been evaluated in populations from the Middle East, which have different dietary patterns compared to the US and Europe. In this study, we evaluated the association between six dietary indices and mortality in the Golestan Cohort Study (GCS) in Iran, which is the largest prospective study in the Middle East with 50,045 participants. Methods The six dietary indices, namely the Healthy Eating Index (HEI-2015), Alternative Healthy Eating Index (AHEI-2010), Alternative Mediterranean Diet (AMED), Dietary Approach to Stop Hypertension created by Fung (DASH-Fung) and Mellen (DASH-Mellen), and the World Cancer Research Fund (WCRF/AICR) index, were applied to data from a food frequency questionnaire, computed and divided into quintiles. Adjusted Cox models were used to estimate hazards ratio (HR) and 95% confidence intervals (CI) for overall and cause-specific mortality, using the lowest quintile as a reference group. Results Among 42,373 participants included in the current analyses, 4424 subjects died during 10.6 years of follow-up. Participants with the highest quintile dietary scores, compared with the lowest quintile dietary scores, had significantly decreased overall mortality in the AHEI-2010, AMED, DASH-Fung, and WCRF/AICR indices (HR 0.88, 95% CI = 0.80-0.97; 0.80, 0.70-0.91; 0.77, 0.70-0.86; and 0.79, 0.70-0.90, respectively). A reduced cardiovascular mortality was found for high AHEI-2010 and DASH-Fung scores (17% and 23%, respectively), and a reduced cancer mortality for high HEI-2015, AMED, and DASH-Fung scores (21, 37 and 25%, respectively). Conclusion Various indices of dietary quality are inversely associated with overall mortality, and selectively with cancer and cardiovascular mortality in the GCS, which contribute to the generalizability and validity of dietary guidelines.

Fruit and vegetable consumption and breast cancer incidence: Repeated measures over 30 years of follow-up.

We evaluated the relation of fruit and vegetable consumption, including specific fruits and vegetables, with incident breast cancer characterized by menopausal status, hormone receptor status and molecular subtypes. Fruit and vegetable consumption, cumulatively averaged across repeated, validated questionnaires, was examined in relation to risk of invasive breast cancer among 182,145 women initially aged 27-59 years in the Nurses' Health Study (NHS, 1980-2012) and NHSII (1991-2013). Cox proportional hazards regression, adjusted for known risk factors, was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) and assessed tumors by hormone receptor status and molecular subtypes. We prospectively documented 10,911 invasive breast cancer cases. Greater intake of total fruits and vegetables, especially cruciferous and yellow/orange vegetables, was associated with significantly lower breast cancer risk (>5.5 vs. ≤2.5 servings/day HR = 0.89, 95% CI = 0.83-0.96; ptrend = 0.006). Intake of total vegetables was especially associated with lower risk of estrogen receptor negative tumors (HR per 2 additional servings/day as a continuous variable = 0.84, 95%CI = 0.77-0.93; pheterogeneity = 0.02). Among molecular subtypes, higher intake of total fruits and vegetables (HR per 2 additional servings/day as a continuous variable) was most strongly associated with lower risk of human epidermal growth factor receptor 2 (HER2)-enriched (HR = 0.79, 95%CI = 0.67-0.93), basal-like (HR = 0.84, 95%CI = 0.72-0.97) and luminal A (HR = 0.94, 95%CI = 0.89-0.99), but not with luminal B tumors (pheterogeneity = 0.03). In conclusion, our findings support that higher intake of fruits and vegetables, and specifically cruciferous and yellow/orange vegetables, may reduce the risk of breast cancer, especially those that are more likely to be aggressive tumors.