Vitamin B12 and folic acid associated megaloblastic anemia: Could it mislead the diagnosis of breast cancer?

Abstract

CA 15-3 is a tumor-associated antigen and is overexpressed in breast tumors, and may also be high in some other non-cancerous conditions. The aim of this study was to investigate the effect of megaloblastic anemia due to vitamin B12 or folic acid deficiency on the levels of tumor markers. Five-year patient data were retrospectively analyzed. The associations between megaloblastic anemia due to vitamin B12 deficiency and CA 15-3, CA 125, CA 19-9, CEA, and AFP levels were analyzed. Furthermore, association between CA 15-3 level and megaloblastic anemia due to folic acid deficiency was evaluated. Median CA 15-3 level was 38.1U/mL in the group with megaloblastic anemia due to vitamin B12 deficiency(n=15), 46.7U/mL in the group with megaloblastic anemia related to folic acid deficiency (n=3), and 17.8U/mL in the normal group(n=1724). CA 15-3 levels were significantly higher among patients with vitamin B12- and folic acid-associated megaloblastic anemia compared to the normal group (p=0.001 and p=0.005, respectively). Megaloblastic anemia due to vitamin B12 deficiency was not associated with any significant differences in CA 125, CA 19-9, CEA, or AFP levels compared to the normal group (p=0.777, p=0.327, p=0.577, and p=0.197, respectively). The numbers of anemic and normal subjects compared in these tests were 12 vs. 1501, 17 vs. 1827, 4 vs. 897, and 8 vs. 1041, respectively. In conclusion, megaloblastic anemia results in ineffective erythropoiesis, and increased levels of CA 15-3 may be associated with this issue. Clinicians should take this into account when evaluating for a pre-diagnosis of breast cancer.