Tumor Ki-67, ER and PR, and antibodies against estradiol and progesterone in breast cancer patients

Aim . To investigate the associations of cell proliferation marker Ki-67 in estrogen receptor (ER) and progesterone receptor (PR) positive (ER + / PR + ) and negative (ER - /PR - ) tumors with the ratio of antibodies against estradiol and progesterone (IgA 1 -E2/IgA 1 -Pg) in the serum of breast cancer (BC) patients. Materials and Methods . Antibodies against steroid hormones were analyzed by ELISA in the serum of 432 healthy women and 1212 patients with BC (573 patients with I stage and 639 patients with II–IV stages). Expression of Ki-67, ER and PR in tumors was determined by immunohistochemical staining. Serum estradiol and progesterone were measured by enzyme-linked immunosorbent assay. Results . In total, low IgA 1 -E2/IgA 1 -Pg (≤ 1) and high IgA 1 -E2/IgA 1 -Pg (> 1) ratio were revealed in 49.3% and 50.7% of healthy women; in 25.7% and 74.3% of stage I BC patients with tumor Ki-67 < 14 (р < 0.001; OR = 0.4 and OR = 2.8, respectively), and in 17.1% and 82.9% of stage I BC patients with tumor Ki-67 > 30 (р < 0.001; OR = 0.2 and OR = 4.7, respectively). The differences between patients with low and high tumor Ki-67 levels in relation to low and high IgA 1 -E2/IgA 1 -Pg ratio were statistically significant (p = 0.03). In stage I BC patients with ER + /PR + and tumors with Ki-67 < 14, low and high IgA 1 -E2/IgA 1 -Pg ratio were found in 25.0% and 75.0% cases (р < 0.001; OR = 0.3 and OR = 2.9, respectively). In stage I BC patients with ER + /PR + and tumors with Ki-67 > 30, low and high IgA 1 -E2/IgA 1 -Pg ratio were found in 12.9% and 87.1% cases (р < 0.001; OR = 0.2 and OR = 6.6, respectively). In patients with ER + /PR + tumors, the differences between patients with low and high tumor Ki-67 levels in relation to low and high IgA 1 -E2/IgA 1 -Pg ratio were also statistically significant (p = 0.009). In patients with ER - /PR - tumors, the differences between patients with low and high Ki-67 levels in relation to low and high IgA 1 -E2/IgA 1 -Pg ratio were not revealed. The proportion of breast cancer patients with tumor Ki-67 > 30 increased from I to II–IV BC stages regardless of IgA 1 -E2/IgA 1 -Pg ratio. Conclusion . IgA 1 -E2/IgA 1 -Pg ratio may serve as a predictor of tumor proliferative activity in stage I BC patients with ER + /PR + tumors.