Immune reactions to clinical carcinogens and steroid hormones in breast pre-cancer and cancer patients

Abstract

Detection of postmenopausal women at high risk for breast pre-cancer and cancer is a key condition to prevent these diseases. Aim of our research was to study possible usage of immunoassay for antibodies specific to benzo[a]pyrene, estradiol, and progesterone (IgA-Bp, IgA-Es, IgA-Pg) in determination of personal risks for fibrocystic disease and breast cancer at the early stage, with respect to hormone receptor status in tumor tissues. Blood serum IgA-Bp, IgA-Es, IgA-Pg were studied by ELISA in postmenopausal women: healthy controls (n = 401), patients with fibrocystic breast disease (n = 50), and breast cancer (stage I, n = 575, stages II-IV, n = 861). High individual IgA-Bp/IgA-Pg ratios of 1.5 were found in 19.7% of healthy women, and in 50.0% of fibrocystic breast disease patients (p 0.0001; OR = 4.1). IgA-Es/IgA-Pg ratios of 1.0 were revealed in 48.4% healthy women and in 68.0% fibrocystic breast disease patients (p 0.01; OR = 2.3). IgA-Bp/IgAPg values 1.0 were found in 41.9% of healthy women, and, at higher rates, in the patients with breast cancer stage I: 68.3% ER- tumors (p 0.0001; OR = 3.0) and 75.9% ER+ tumors (p 0.0001; OR = 4.4). IgA-Es/ IgA-Pg ratios 1.0 were revealed in 48.4% of healthy women, and in patients with breast cancer stage I: 65.3% ER- tumors (p 0.003; OR = 2.0), and 76.8% ER+ tumors (p 0.0001; OR = 3.5). Some associations of studied antibodies with cancer progression were revealed. Frequency of individual cases with IgA-Bp/IgA-Pg 1.0 in patients with ER- tumors increased from 12.0% at stage I to 19.9% at stage II. Frequency of cases with IgA-Bp/IgA-Pg 1.0 in the patients with ER+ tumors decreased from 62.0% at stage I to 57.3% at stage II (p = 0.002). Frequency of cases with IgA-Es/IgA-Pg 1.0 in the patients with ER- tumors increased from 11.5% at stage I to 21.4% at stage II. Frequency of cases with IgA-Es/IgA-Pg 1.0 in patients with ER+ tumors decreased from 63.3% at stage I to 56.1% at stage II (p 0.001). The cases with individual excessive IgA-Bp and IgA-Es levels are associated with fibrocystic breast disease and ER+ breast cancer at the onset of the disease. Breast cancer progression was associated with the relative decrease of ER in tumor tissues, along with higher individual levels of IgA-Bp and IgА-Es and lower IgA-Pg levels. ELISA testing of IgА-Bp, IgА-Es, IgA-Pg could be recommended for detection of individual risk for fibrocystic breast disease and stage I of breast cancer, as well as for more efficient prevention and therapy by selective modulators of estrogen receptor (raloxifene, arzoxifene and lasofoxifine) and aromatase inhibitors (exemestane, anastrozole).