No tool to measure diet quality on the global scale currently exist. At the same time, type 2 diabetes is a global issue for women, including those under age 50. As part of an effort to develop an instrument to assess diet quality, this analysis the ability of a global diet quality score to predict type 2 diabetes in women in a high-income country. Therefore, the objective of this analysis is to examine prospectively the association between the Global Diet Quality Score (GDQS) and risk of type 2 diabetes, and potential differences in association by age, among U.S. women. Health, lifestyle, and diet information was collected from women (n = 88,520) in the Nurses' Health Study II through repeated questionnaires between 1991 and 2017. The GDQS consisted of 25 food groups and points were awarded for higher intake of healthy groups and lower intake of unhealthy groups (maximum of 49 points). Multivariable hazard ratios (HR) were computed for confirmed type 2 diabetes using Cox proportional hazards models. We ascertained 6319 incident type 2 diabetes during follow-up. The multivariable HR comparing top to bottom quintile of GDQS was 0.83 (95% CI = 0.76–0.91, p trend < 0.001). The association for women under age 50 was 0.77 (0.68–0.88, p trend < 0.001) and for age 50+ was 0.69 (0.52–0.93, p trend < 0.001) with no significant interaction. Analysis of the healthy and unhealthy subscores of the GDQS showed an inverse association with lower intake of unhealthy components (HR comparing top to bottom quintile of the unhealthy subscore = 0.69, 95% CI = 0.62–0.77, p trend < 0.001) but not higher intake of healthy components. The inverse association for each 1-SD increase in the GDQS (HR = 0.93, CI = 0.91–0.96) was stronger (P < 0.001) than the Minimum Diet Diversity score for Women (MDDW) (HR = 1.00, CI = 0.94–1.04) but slightly weaker (P = 0.03) than the Alternate Healthy Eating Index-2010 (AHEI-2010) (HR = 0.91, CI = 0.88–0.94). A higher GDQS was inversely associated with type 2 diabetes risk in U.S. women, mainly due to lower intake of unhealthy foods. The association did not appear to differ by age. The GDQS performed nearly as well as the AHEI-2010. Funding for this work was provided by Intake - Center for Dietary Assessment at FHI Solutions.
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.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.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.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.
Abstract 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.
Electric and magnetic fields (EMFs) have been hypothesized to increase the risk of breast cancer, and electric blankets represent an important source of exposure to EMFs. The authors examined the relation between electric blanket use and invasive breast cancer in the Nurses' Health Study. On the biennial questionnaire in 1992, 87,497 women provided information on this exposure during three consecutive time periods. In a prospective analysis with 301,775 person-years of follow-up through 1996 (954 cases), the relative risk for any electric blanket use was not elevated (relative risk (RR) = 1.08, 95% confidence interval (CI): 0.95, 1.24) after controlling for breast cancer risk factors. There was a weak association between breast cancer and electric blanket use at least 16 years before diagnosis and long-term use in age-adjusted analyses but not in multivariate models. In a retrospective analysis of 1,318,683 person-years of follow-up (2,426 cases), the multivariate relative risk associated with use before disease follow-up began was null (RR = 1.05, 95% CI: 0.95, 1.16). Similar results were obtained in analyses stratified by menopause and restricted to estrogen receptor-positive breast cancers. While 95% confidence intervals for these estimates did not exclude small risks, overall, results did not support an association between breast cancer risk and exposure to EMFs from electric blankets.
360922 Background: In-vitro and in-vivo evidence suggests that aspirin may have an anti-tumor effect. Multiple epidemiologic studies have reported improved breast cancer survival among regular aspirin users compared to non-users. Pooled data from randomized trials of aspirin for cardiovascular disease have also reported a decreased risk of metastatic cancer among aspirin users. Thus, we conducted a prospective randomized controlled trial to determine the true benefits and risks of adjuvant aspirin therapy for breast cancer survivors. Methods: The primary objective was to compare the effect of 300 mg aspirin daily versus placebo upon invasive disease-free survival (iDFS) in patients with high-risk, HER2-negative breast cancer. Secondary objectives included effects on overall survival, cardiovascular disease, toxicity, and adherence. Eligible participants included patients aged 18-70 diagnosed with a primary invasive HER2-negative breast cancer. If hormone receptor (HR)–positive, tumors needed to be node positive and diagnosed within the past 10 years. If HR negative, tumors could be node positive or T2-4N0 and diagnosed within the past 18 months. Participants were randomly selected (1:1) to aspirin 300 mg versus placebo daily for 5 years in a double-blinded fashion. Stratification factors include HR status (positive vs. negative), body mass index (< or ≥ 30 kg/m2), and stage (II vs. III). Based upon an accrual goal of 2,936 patients to reach 381 iDFS events, the study was estimated to have 80% power to detect HR 0.75. Results: From January 2017 to December 2020, 3,021 participants were enrolled. Treatment arms were well balanced in terms of key characteristics. In November 2021, the Data Safety and Monitoring Board recommended that the trial be unblinded because the stratified hazard ratio had crossed a pre-specified futility boundary. After 191 iDFS events (aspirin: 107, placebo: 84) and median follow-up of 20 months, the stratified hazard ratio comparing aspirin to placebo was 1.27 (z-score: -1.64), which is greater than the pre-specified hazard ratio of futility 1.03 (z-score < -0.192). There was no difference in the frequency of grade 3/4 adverse events by study arm. Compliance was high and similar across arms. Non-protocol use of aspirin/non-steroidal anti-inflammatory drugs was similar across arms and less than 14%, consistent with prior randomized aspirin trials. Updated results on iDFS events will be provided at presentation. Conclusions: In this double-blinded, placebo-controlled, randomized trial, there was no benefit in breast cancer invasive disease-free survival with the addition of 300 mg aspirin daily. Although inflammation may still play a role in cancer progression, aspirin is not recommended for prevention of breast cancer recurrence. Clinical trial information: NCT02927249.
PURPOSE: To examine the relationship between plasma levels of reproductive sex steroid hormones in postmenopausal women and their reported fat intake. METHODS: We measured plasma sex steroid hormones levels in plasma collected in 1989 and 1990 from 381 healthy postmenopausal women. For each woman, we measured fat intake in 1986 and 1990 by a food-frequency questionnaire. The cross-sectional associations between the percentage of energy from total and specific types of dietary fat intake and plasma hormone levels were assessed by linear regression, controlling for energy intake, obesity, and protein intake. RESULTS: The plasma estradiol level was 4.3% lower (95% confidence limits, −8.3%, −0.2%) for a substitution of 5% of energy from fat intake for an equivalent amount of energy from carbohydrate when adjusted for obesity and other covariates. Estradiol was also inversely associated with all other fat types except trans fat; the inverse associations with vegetable fat and marine omega-3 fats were statistically significant. CONCLUSION: We observed an inverse association between total fat intake averaged over 4 to 5 years and estradiol levels. This result is inconsistent with the hypothesis that fat intake predisposes to breast cancer risk by raising endogenous estrogen levels.
We examined whether a history of smoking is associated with an increased risk of death from any cause or from breast cancer, among women diagnosed with breast cancer. This was a prospective observational study among 5,056 women from the Nurses' Health Study with Stages I-III invasive breast cancer diagnosed between 1978 and 2002 and for whom we had information on smoking, and who were followed until January 2002 or death, whichever came first. Subjects were classified as current, former or never smokers based upon smoking status at the biennial questionnaire immediately preceding the breast cancer diagnosis. In multivariate-adjusted analyses, compared with never smokers, women who were current smokers had a 43% increased adjusted relative risk (RR) [95% confidence interval (95% CI): 1.24-1.65] of death from any cause. A strong linear gradient was observed with the number of cigarettes per day smoked, p-trend <0.0001; the RR (95% CI) for 1-14, 15-24 and 25 or more cigarettes per day was 1.27 (1.01-1.61), 1.30 (1.08-1.57) and 1.79 (1.47-2.19). In contrast, there was no association with current smoking and breast cancer death; the RR (95% CI) was 1.00 (0.83-1.19). Current and past smokers were more likely than never smokers to die from primary lung cancer, chronic obstructive pulmonary disease and other lung diseases. We conclude that a history of smoking increased mortality following diagnosis with breast cancer, but did not increase mortality from breast cancer.
Abstract Background: Experimental evidence suggests that aspirin may inhibit breast tumor growth and reduce invasiveness of breast cancer cells. In large population-based studies (including our own), post-diagnostic aspirin use was associated with reduced breast cancer-specific and all-cause mortality. Here, we have extended our prior study with an additional 10 years of follow-up (3,785 more breast cancer cases) and investigation of the molecular underpinnings of the role of aspirin in breast cancer prognosis. Methods: Our study included 7,949 women diagnosed with stage I, II or III breast cancer from the Nurses’ Health Study (NHS) and NHSII. Cox proportional hazards regression was used to compute the multivariate hazard ratio (HR) for death, adjusting for tumor characteristics, treatment information and lifestyle factors. Post-diagnostic aspirin use was obtained at least 12 months after diagnosis and updated at every 2-year follow-up interval. We also evaluated the association between post-diagnostic aspirin use and survival according to tumor characteristics. Estrogen receptor (ER), insulin receptor (IR), PTEN, and Ki67 protein expression was evaluated by immunohistochemistry. PIK3CA mutation status was determined via polymerase chain reaction and pyrosequencing. In an exploratory analysis to identify functional enrichment of biologic pathways associated with long-term pre-diagnostic aspirin use (ever use of aspirin for ≥10 years with >2d/wk), we used a competitive gene-set testing procedure in a subgroup of cases with gene expression data (N=453). In this subset, we also computed the abundance of immune cell infiltration (B cell, CD4+ T cell, CD8+T cell, macrophage, neutrophil and dendritic cell) using Tumor IMmune Estimation Resource (TIMER). Results: During a median follow-up of 12 years after breast cancer diagnosis, we documented 2,502 deaths, including 1,373 from breast cancer. Compared with nonusers, women who regularly used aspirin after diagnosis had lower breast cancer-specific mortality: HR for 1, 2-5, 6-7 days of aspirin use per week were 0.65 (95% CI: 0.49, 0.86), 0.41 (95% CI: 0.29, 0.57) and 0.61 (95% CI: 0.47, 0.78) for, respectively (p-trend<0.0001). The association did not differ statistically by PTEN loss, PIK3CA mutation, or expression of IR (PI3K—AKT—mTOR), ER or Ki67 expression (proliferation pathways), or immune cell infiltration of the primary tumors (p-heterogeneity>0.05). Long-term regular aspirin use before diagnosis was associated with the downregulation of pathways related to inflammation (INF-α, INF-γ, and TNF-α), PI3K—AKT—mTOR signaling (mTOR and PI3K—AKT), and other proliferation (E2F and myc targets) in primary breast tumors and/or normal-adjacent tissues (FDR≤0.05). Long-term regular aspirin use prior to diagnosis was also associated with higher CD8+T cell (mean±SD=0.20±0.02 for non-users and 0.21±0.02 for users, p=0.01) and macrophage (mean±SD=0.05±0.03 for non-users and 0.06±0.02 for users, p=0.0002) relative abundance in primary tumors. Conclusion: Regular aspirin use after breast cancer diagnosis was associated with lower risk of breast cancer-specific and total mortality. The association between aspirin and mortality did not differ by molecular characteristics of primary tumors. Long-term aspirin use prior to breast cancer diagnosis was associated with downregulation of inflammatory and proliferation pathways and higher immune cell infiltration of CD8+ T cells and macrophages in breast tumors. Taken together, our large-scale population-based analysis with long-term of follow-up highlight the potential benefit of aspirin as a secondary prevention strategy across different tumor molecular characteristics. Citation Format: Cheng Peng, Michelle D. Holmes, Tengteng Wang, Alexandra Harris, Wendy Chen, Kristen Brantley, Yujing J Heng, Vanessa C. Bret-Mounet, Gabrielle M Baker, Bernard Rosner, Walter Willett, Rulla Tamimi, A. Heather Eliassen. Regular aspirin use, breast tumor characteristics and long-term breast cancer survival [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 P3-12-01.
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