Immuno-hormonal network in postmenopausal women: disturbance in breast cancer patients.

INTRODUCTION: Antibodies to estradiol and progesterone (Es and Pg) modulated their blood serum concentration and biological effects in immunized animals. Antibodies to membrane steroid receptors acted as hormone agonists or antagonists in cell cultures. MATERIAL AND METHODS: Here we studied the levels of Es and Pg, idiotypic immunoglobulin (Ig) A1 and anti-idiotypic IgG2 specific to Es and Pg in the serum of postmenopausal women (82 healthy donors and 443 breast cancer patients). RESULTS: It was found that individual high ratios of Pg/Es (> 4), IgA-Pg1/IgA-Es1 (> 1) and IgG-Pg2/IgG-Es2 (> 1) were associated with low breast cancer risk (OR = 0.4-0.5). High ratios of IgA-Pg1/IgA-Es1 and IgG-Pg2/IgG-Es2 were associated with a high Pg/Es ratio in healthy women but not in breast cancer patients. The levels of idiotypic IgA to benzo[a]pyrene correlated significantly with IgA-Es1 and IgA-Pg1 levels in both compared groups. IgA-Pg1/IgA-Es1 ratio correlated with IgG-Pg2/IgG-Es2 only in healthy women but not in breast cancer patients. CONCLUSIONS: The normal immune-hormonal balance supports the real adaptation of the organism to environmental carcinogens and inhibits the initiation and promotion of carcinogenesis. The disturbance between certain elements of this network (immune-hormonal disbalance) could stimulate carcinogenesis. Further studies of immune-hormonal interaction could be helpful for understanding the pathogenesis of other carcinogen-induced steroid-dependent diseases in humans.

Postmenopausal Breast Cancer Risk in Relation to Antibodies Specific to Benzo[a]Pyrene, Estradiol and Progesterone.

BACKGROUND: Antibodies might protect against low doses of environmental carcinogens by decreasing systemic uptake, activation of metabolic pathways, and redistribution of carcinogens within the organism. The features of antibody formation in relation to environmental carcinogens and sex steroids under natural conditions should be determined to identify breast cancer risk, then to develop cancer immune prevention strategies. OBJECTIVES: The purpose of this study was to investigate antibodies specifications to benzo(a)pyrene, estradiol and progesterone in postmenopausal women with invasive breast cancer. PATIENTS AND METHODS: A semi-quantitative non-competitive immunoassay of IgG antibodies to benzo(a)pyrene (IgG-Bp), estradiol (IgG-Es), and progesterone (IgG-Pg) has conducted. The assay has performed on 322 serum samples from patients with breast cancer and 179 serum samples from healthy postmenopausal women by using low-molecular-weight Bp, Es, and Pg conjugated with bovine serum albumin. ROC analysis has also conducted to determine the odds ratio (OR). RESULTS: Combination of the high levels of IgG-Bp and IgG-Es without IpG-Pg was more frequent in breast cancer patients than that in healthy women, and the OR has increased to 3.8. Combination of the high levels of IgG-Pg with high levels of both IgG-Bp and IgG-Es were significantly more frequent in breast cancer patients (36.9%) than that in healthy women (5.6%), and the OR increased to 11.7. These differences have peculiarly expressed in breast cancer patients with hormone status ER+/PR- (OR = 26.7). The minimum OR (0.4) has obtained at low levels of the three antibodies. CONCLUSIONS: Immunoassay of antibodies against environmental carcinogens and sex steroid hormones could use to detect breast cancer risk. Induction of antibodies against Bp for cancer immunoprevention could lead to antibody formation against steroid hormones, thereby increasing breast cancer risk.

Frequency of EGFR mutations in non-small cell lung cancer patients: screening data from West Siberia.

BACKGROUND: Incorporation of molecular analysis of the epidermal growth factor receptor (EGFR) gene into routine clinical practice has shown great promise to provide personalized therapy of the non-small cell lung cancer (NSCLC) in the developed world. However, the genetic testing of EGFR mutations has not yet become routine clinical practice in territories remote from the central regions of Russia. Therefore, we aimed to study the frequency of major types of activating mutations of the EGFR gene in NSCLC patients residing in West Siberia. MATERIALS AND METHODS: We examined EGFR mutations in exons 19 and 21 in 147 NSCLC patients (excluding squamous cell lung carcinomas) by real time polymerase chain reaction. RESULTS: EGFR mutations were detected in 28 of the 147 (19%) patients. There were 19 (13%) cases with mutations in exon 19 and 9 cases (6%) in exon 21. Mutations were more frequently observed in women (42%, p=0.000) than in men (1%). A significantly higher incidence of EGFR mutations was observed in bronchioloalveolar carcinomas (28%, p=0.019) and in adenocarcinomas (21%, p=0.024) than in large cell carcinomas, mixed adenocarcinomas, and NOS (4%). The EGFR mutation rate was much higher in never-smokers than in smokers: 38% vs. 3% (p=0.000). The frequency of EGFR mutations in the Kemerovo and Tomsk regions was 19%. CONCLUSIONS: The incorporation of molecular analysis of the EGFR gene into routine clinical practice will allow clinicians to provide personalised therapy, resulting in a significant increase in survival rates and improvement in life quality of advanced NSCLC patients.