Associations of steroid-specific immunological phenotypes with tumor cell proliferation in breast cancer patients: CART analysis

Aim. To study the associations between IgA and IgG autoan tibodies against estradiol and progesterone (IgA1-E2 and IgA1 Pg; IgG1-E2 and IgG1-Pg) and the corresponding anti-idiotyp ic IgG autoantibodies (IgG2-E2 and IgG2-Pg) with tumor Ki-67 expression in breast cancer patients. Materials and Methods. Idiotypic and anti-idiotypic antibodies specific to steroid hor mones were studied in the sera of 1,115 postmenopausal women with breast cancer (stage I: 525 patients, stages II–IV: 590 pa tients) prior to treatment by enzyme-linked immunosorbent as say. Tumor Ki-67 expression was determined by an immunohis tochemical staining. Associations were analyzed using CART (Classification and Regression Tree) analysis. Results. Among patients with stage II–IV breast cancer, six groups with distinct individual combinations of antibody levels (immunological phe notypes) were identified, each associated with Ki-67 expression in tumors. High levels of Ki-67-positive cells in tumors (> 20 %) were found in: 1) 53.3 % patients with IgG 2 -Pg ≤ 1.9+ IgA 1 -Pg ≤ 2.2 + IgG2-E2 ≤ 4.1; 2) 85,0 % patients with IgG 2 -Pg ≤ 1.9 + IgA 1 -Pg ≤ 2.2 + IgG 2 -E2 > 4.1 (p = 0.011 vs 1 group); 3) 87.2 % patients with IgG 2 -Pg ≤ 1.9 + IgA 1 -Pg > 2.2; 4) 82.7 % patients with IgG 2 -Pg > 1.9 + IgA 1 -Pg < 0.7; 5) 58.5 % patients with IgG 2 -Pg = 1,9–4,1 + IgA 1 -Pg > 0,7 (p = 0.012 vs 4 group); 6) 39.7 % patients with IgG 2 -Pg > 4.1 + IgA 1 -Pg > 0.7 (p = 0.008 vs 5 group). An increased proportion of patients with Ki-67 > 20 % at stages II–IV compared with stage I (p < 0.001) was ob served in groups 2, 3, 4, and 5. Suppression of tumor cell prolif eration was seen in groups 1 and 6. Conclusion. Enzyme-linked immunosorbent assay measurements of IgG 2 -Pg, IgA 1 -Pg, and IgG1-E2 may be useful for predicting tumor proliferative activ ity in stage I breast cancer patients during further disease pro gression.