Synergistic action of steroid hormones and hormone-specific autoantibodies in breast cancer progression

Aim. To study the possible synergistic action of steroid hormones and hormone-specific autoantibodies and anti-autoantibodies in conversion of ER+/PR+ tumors into ER-/PR- in breast cancer patients.Materials and Methods. Concentrations of estradiol (E2) and progesterone (Pg) and the levels of hormone-specific idiotypic IgA antibodies (IgA1-E2 and IgA1-Pg) as well as anti-idiotypic IgG antibodies (IgG2-E2 and IgG2-Pg) were studied in the serum of 979 breast cancer patients (432 patients with stage 1 and 547 patients with stages 2-4) by means of enzyme-linked immunosorbent assay. E2 and Pg receptors phenotype (ER/ PR) was determined using immunohistochemistry.Results. Simultaneous increase in IgA1-E2 and IgG2-E2 levels was associated with elevated E2 serum concentration (p = 0.007) in ER+/PR+ breast cancer patients. On the contrary, concurrent increase in IgA1-Pg и IgG2-Pg, was associated with lowered Pg concentration (p = 0.04). The frequency of ER+/PR+ tumors was low and ER-/PR- was high in patients with stages 2-4 breast cancer than in stage 1 in the following cases: 1) IgG2-E2 and IgA1-E2 levels were high regardless of serum E2 (p = 0.004); 2) IgG2-E2 levels were high and IgA1-E2 and E2 levels were low (p = 0.002); 3) IgG2-Pg and Pg levels were high regardless of IgA1-Pg levels (р < 0,001); 4) IgG2-E2 and IgG2-Pg levels were high regardless of E2, Pg, IgA1-E2 and IgA1-Pg levels (р < 0,001). In other combinations of hormones and hormone-specific antibodies and anti-antibodies, there have been no differences in the frequency of ER+/PR+ and ER-/PR- tumors between patients with ascending stages of breast cancer.Conclusion. We for the first time found a synergistic action of hormone-specific idiotypic and anti-idiotypic autoantibodies on the concentration of steroid hormones in the serum of breast cancer patients, and the synergistic action of steroid hormones and hormone-specific idiotypic and anti-idiotypic autoantibodies on tumor steroid receptor conversion.