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The role of vitamin D and calcium use in the development of breast cancer among women in the general population is not clear. Furthermore, whether vitamin D and calcium supplement use are associated with breast cancer in high-risk populations has not been evaluated. Thus, we evaluated the association between vitamin D and/or calcium supplement use and breast cancer among women with a pathogenic variant (mutation) in BRCA1 or BRCA2. BRCA mutation carriers enrolled in a longitudinal study were invited to complete a supplemental questionnaire on lifetime supplement use. Cases included women with a prevalent diagnosis of invasive breast cancer, and controls had no history of breast cancer. Vitamin D and calcium use were categorized as never/ever use, and as tertiles of supplement intake (total average daily supplement use). Unconditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence intervals (CIs) of breast cancer. This study included 134 breast cancer cases and 276 controls. Women who used vitamin D-containing supplements had 46% lower odds of having breast cancer compared to those who never used supplements (OR 0.54; 95% CI 0.31, 0.91; p = 0.02). Increasing vitamin D and calcium supplement intake was inversely associated with the odds of having breast cancer (p-trend = 0.04). Findings were suggestively stronger among BRCA1 mutation carriers; however, analyses were limited by small strata. These findings suggest a potential inverse association between vitamin D and calcium supplementation and BRCA breast cancer. Additional studies are warranted to confirm these findings and accurately inform clinical care guidelines.

Background: Use of vitamin D and calcium-containing supplements are associated with a decreased risk of breast cancer among women in the general population. Whether this association exists among women at a high-risk due to a BRCA1 or BRCA2 mutation is not known. Thus, we conducted a case-control study to evaluate the association between vitamin D and/or calcium supplement use and the risk of breast cancer among BRCA mutation carriers. Methods: BRCA mutation carriers enrolled in a longitudinal study, that collected information on cancer history and lifestyle factors, were invited to complete a supplemental questionnaire on past supplement use. Vitamin D and calcium supplement use were categorized as never or ever use. Total average daily vitamin D and calcium use was stratified as never, moderate, or high intake based on tertiles. Unconditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence intervals (CI) of invasive breast cancer associated with supplement use. Analyses were stratified by BRCA mutation type and menopausal status at breast cancer diagnosis. Results: This study included 134 cases and 276 controls. Compared to never users, ever vitamin D or calcium-containing supplement use was associated with decreased odds of breast cancer (OR=0.54; 95%CI 0.31, 0.91; P=0.02 for vitamin D; OR=0.61; 95%CI 0.36, 1.05; P=0.07 for calcium). The protective effect of vitamin D and calcium was stronger for those with the highest intake of each supplement (OR=0.44; 95% CI 0.22, 0.89; P=0.02 for vitamin D; OR=0.55; 95% CI 0.28, 1.08; P=0.08 for calcium), compared to never use. For vitamin D use, findings were significant among premenopausal women while for calcium use, the inverse associations were stronger among postmenopausal women. Findings were also significant for BRCA1 mutation carriers only, however, stratified analyses were limited by small strata. Conclusions: Although based on a relatively small sample, our findings suggest a potential protective effect of vitamin D and calcium-containing supplement use for breast cancer among high-risk women. Future studies with larger samples and prospective study design are warranted. Citation Format: Emma Guyonnet, Shana J. Kim, Cindy X. Zhang, Jeanna McCuaig, Susan Armel, Steven A. Narod, Joanne Kotsopoulos. Vitamin D, calcium supplement use and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers: A case-control study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5942.

Background: The empirical dietary inflammatory pattern (EDIP) is a hypothesis-driven dietary pattern used to assess the inflammatory potential of diet in the US population. Food-frequency questionnaire responses are used to build regression models comparing this dietary information to circulating inflammatory profiles, to help determine which food groups have more or less inflammatory potential on specific individuals. We will eventually use this tool in a cancer patient intervention to modify inflammation and improve chances of survival. Methods: EDIP scores were calculated for 4 models from 24hr recalls reported by 67 women noncancer controls that had signed an informed consent prior to participation. The Luminex Human Chemokine Multiplex Assay was used to measure 11 chemokines and cytokines. As seen in previous studies, we first derived a model, EDIP-Limited (EDIP-L), by using a reduced rank regression model of all 17 food groups followed by a multivariable regression analysis to identify a dietary pattern that predicts concentrations of two inflammatory biomarkers: IL-6 and TNF-a. We derived a secondary EDIP score using a new model, EDIP-All Inclusive (EDIP-AI), which included the same 17 food groups to predict all 11 circulating biomarkers in our panel. Lastly, we developed two additional EDIP models to test how the biomarker predication may change when we regrouped our food variables from 17 to 14 groupings. EDIP-Limited New (EDIP-LN) used 14 new food groups derived from the same 24hr recalls, only predicting IL-6 and TNF-a. EDIP-All New (EDIP-AN) used those same 14 food groups with all 11 biomarkers. Results: In this study, we optimize models for EDIP and report the differences in EDIP scores based on the inflammatory biomarkers and food groups used in analysis. Briefly, the components of EDIP-L were not significant. After including all the biomarkers, the components of EDIP-AI were: “fruit juice” (p = 0.0009), “snacks” (p = 0.0008), “leafy green vegetables” (p = 0.0074), “low-energy beverages” (p = 0.0098), “red meat” (p = 0.0038), “fruit” (p = 0.0002) and “whole wheat grains” (p = 0.0138). Similarly, after reorganizing our food items into 14 food groups, the components of EDIP-LN were not significant. However, components of EDIP-AN were: “fruit juice” (p = 0.0107), “snacks” (p = 0.0116) and “fruit” (p = 0.0026). Conclusions: Findings demonstrate the EDIP scores differ based on the inflammatory biomarkers and food groups used in the analysis on the same noncancer controls. Depending on the methods used, an individual’s diet may be considered more pro- or anti-inflammatory. This study provides insight into the inflammatory potential of an individual’s diet and the factors that may affect how we calculate this potential.

Background: The empirical dietary inflammatory pattern (EDIP) is a hypothesis- driven dietary pattern used to assess the inflammatory potential of diet in the US population. It is usually composed of food groups obtained from a food-frequency questionnaire. Methods: EDIP scores were calculated for 4 models from 24hr recalls reported by 67 women noncancer controls that had signed an informed consent prior to participation. The Luminex Human Chemokine Multiplex Assay was used to measure 11 chemokines and cytokines. As seen in previous studies, we first derived a model, EDIP-Limited (EDIP-L), by entering 18 food groups in reduced rank regression models followed by a multivariable regression analysis to identify a dietary pattern that predicts concentrations of two inflammatory biomarkers: IL-6 and TNF-a. We derived another EDIP score using a new model, EDIP-All Inclusive (EDIP-AI), which included the same 18 food groups to predict all 11 biomarkers. Lastly, we developed two other EDIP models. EDIP-Limited New (EDIP-LN) used 14 new food groups derived from the same 24hr recalls, only predicting IL-6 and TNF-a. EDIP-All New (EDIP-AN) used those 14 food groups with all 11 biomarkers. Results: In this study, we optimize models for EDIP and report the differences in EDIP scores based on the inflammatory biomarkers and food groups used in analysis. Briefly, the components of EDIP-L were not significant. After including all the biomarkers, the components of EDIP-AI were: “fruit juice” (p = 0.0009), “snacks” (p = 0.0008), “leafy green vegetables” (p = 0.0074), “low-energy beverages” (p = 0.0098), “red meat” (p = 0.0038), “fruit” (p = 0.0002) and “whole wheat grains” (p = 0.0138). Similarly, after reorganizing our food items into 14 food groups, the components of EDIP-LN were not significant. However, components of EDIP-AN were: “fruit juice” (p = 0.0107), “snacks” (p = 0.0116) and “fruit” (p = 0.0026). Conclusions: Findings demonstrate the EDIP scores differ based on the inflammatory biomarkers and food groups used in the analysis on the same noncancer controls. Depending on the methods used, an individual’s diet may be considered more pro- or anti-inflammatory. This study provides insight into the inflammatory potential of an individual’s diet and the factors that may affect how we calculate this potential. Citation Format: Emma Guyonnet, Millicent Amankwah, Yalei Chen, Rachel Martini, Melissa Davis, Lisa Newman. Development of Empirical Dietary Inflammatory Pattern (EDIP) scores with different food groups and biomarkers [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-142.