Associations of antibodies to benzo[a]pyrene, estradiol and progesterone with estrogen receptor phenotype in breast cancer tissue

Aim. To reveal the associations of IgA antibodies to benzo[a]pyrene, estradiol and progesterone (IgA-Bp, IgA-Es, IgA-Pg) with the conversion of estrogen-receptor positive (ER+) into estrogen-receptor negative (ER-) tumors during breast cancer progression.Materials and Methods. Having collected serum samples from 338 healthy volunteers and 1407 breast cancer patients, we have profiled them for IgA-Bp, IgA-Es, IgA-Pg by means of enzyme-linked immunosorbent assay. Conjugates of bovine serum albumin with Bp, Es and Pg were used as adsorbed antigens and anti-human IgA horseradish peroxidase-conjugated antibodies were used for the detection of specific antigen-bound antibodies. Individual IgA-Bp/IgA-Pg and IgA-Es/IgA-Pg ratios were calculated. Estrogen receptor phenotype was determined using immunohistochemistry.Results. Low IgA-Bp/IgA-Pg ratios (≤ 1) in combination with low IgA-Es/IgA-Pg ratios (≤ 1) indicative of protective immunophenotype were more frequently revealed in healthy women (43.8%) in comparison with stage 1 breast cancer patients with ER+ (12.9%) and ER- (23.9%) tumors. High IgA-Bp/IgA-Pg ratios (>1) with high IgA-Es/IgA-Pg ratios (>1) suggestive of pro-carcinogenic immunological phenotype were less often detected in healthy women (27.5%) as compared with stage 1 breast cancer patients with ER+ (65.5%) and ER- (58.7%) tumors. Prevalence of protective and pro-carcinogenic phenotypes significantly differed in stage 1breast cancer patients with ER+ and ER- tumor phenotypes (p = 0.017). ER- tumor phenotype was more prevalent at II-IV tumor stages (25.6%) than at the stage 1 (16.3%). Conversion of ER+ to ER- tumors reflecting the breast cancer progression was characteristic for the patients with pro-carcinogenic immunological phenotype (p<0.0001).Conclusion. Detection of antibodies against Bp, Es and Pg may be applied as a risk marker of breast cancer development and progression.