Serum calcium levels, TRPM7, TRPC1, microcalcifications, and breast cancer using breast imaging reporting and data system scores

Abstract

Shravya Mandavilli,1 Brij B Singh,2 Abe E Sahmoun11Department of Internal Medicine, University of North Dakota School of Medicine and Health Sciences, Fargo, ND, USA; 2Department of Biochemistry and Molecular Biology, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, USABackground: An association between higher serum calcium (Ca2+) levels and breast cancer has been previously reported. However, little is known regarding the relationship between serum Ca2+ levels and the expression of Ca2+ channels in the presence of breast microcalcifications.Methods: A retrospective analysis of women newly diagnosed with breast microcalcifications was performed based on the Breast Imaging Reporting and Data System (BI-RADS). The expression of TRPC1, TRPC3, and TRPM7 using normal biopsy without microcalcifications (controls) and infiltrating ductal carcinoma with microcalcifications was evaluated.Results: Data on 138 women were analyzed. Seventy percent of women had a BI-RADS score (1–3) corresponding to benign disease. Seventy-six percent of women with a BI-RADS score (4 or 5) were diagnosed with breast cancer, 56% were cancers in situ, and 93% were infiltrating ductal carcinomas. No difference in the distribution of corrected serum Ca2+ levels between BI-RADS scores (1–3) and BI-RADS scores (4–5) (P = 0.82) was observed. Serum Ca2+ levels were similar in women without cancer and women diagnosed with breast cancer (P = 0.94). However, the expression of TRPM7 and TRPC1, but not TRPC3, Ca2+ channels were increased in infiltrating ductal carcinoma samples with microcalcifications when compared with age-matched controls without calcification or cancer.Conclusion: We observed an increase in the expression of TRPM7 and TRPC1 Ca2+ channels in infiltrating ductal carcinoma samples with microcalcifications, whereas no change in serum Ca2+ levels was observed. Together these data suggest that increased expression of these channels might lead to an increase in intracellular Ca2+ levels thereby restoring serum Ca2+ levels, but these can contribute to the breast microcalcifications. However, future studies exploring the intracellular Ca2+ levels as well as the role of TRPM7 and TRPC1 function according to BI-RADS scores are needed.Keywords: breast microcalcifications, BI-RADS, Ca2+, ductal carcinoma, TRPC1, TRPM7