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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.