Epidemiology of breast cancer (BC) is the most studied, not only because of the high incidence of this tumor, but also of the significant aesthetic and social importance of this organ for women [2,5]. The incidence of breast cancer holds a leading place for more than 20 years in the structure of cancer pathology in women in the Russian Federation and in the Altai region [5,8]. There are no trends in decreasing of morbidity: in 2002 in the Russian Federation this parameter was 38.89 per 100 thousand (%ooo, standardized parameter), in 2012 - 46.17%ooo (increase during past 10 years - 19.94%) [5]. There is the same trend in the Altai region: the growth of "rough" parameter of the incidence of breast cancer in the period 2004-2012 was 28.2%, the standardized parameter - 46.76%ooo in 2012 [5]. Breast cancer - one of the 3 malignant neoplasms (MN) which is designed for mammography screening, which significantly reduces the mortality from this MN in women aged 50-69 years [2,7,9,15]. Today, multiple risk factors are studied and identified enabling the development of oncological risk group, which aims is the prevention and early diagnosis of breast cancer [1,3,6,12,19,23]. It is proved that up to 10% of malignant breast tumors are genetically determined and, perhaps, the most of molecular genetic studies in oncology are focused on breast cancer problems [10,13,14,16,17,24]. At the same time, despite the many advances in the prevention and diagnosis of this disease, the high levels of mortality are stably maintained. Mortality from breast cancer in the Altai region in 2013 was 28.1%ooo (in the Russian Federation in 2012 - 29.8%ooo) [5]. Thus, the problem of prevention of malignant tumors of the breast is not yet resolved and remains extremely relevant.

Epidemiology of breast cancer (BC) is the most studied, not only because of the high incidence of this tumor, but also of the significant aesthetic and social importance of this organ for women [2,5]. The incidence of breast cancer holds a leading place for more than 20 years in the structure of cancer pathology in women in the Russian Federation and in the Altai region [5,8]. There are no trends in decreasing of morbidity: in 2002 in the Russian Federation this parameter was 38.89 per 100 thousand (%ooo, standardized parameter), in 2012 - 46.17%ooo (increase during past 10 years - 19.94%) [5]. There is the same trend in the Altai region: the growth of "rough" parameter of the incidence of breast cancer in the period 2004-2012 was 28.2%, the standardized parameter - 46.76%ooo in 2012 [5]. Breast cancer - one of the 3 malignant neoplasms (MN) which is designed for mammography screening, which significantly reduces the mortality from this MN in women aged 50-69 years [2,7,9,15]. Today, multiple risk factors are studied and identified enabling the development of oncological risk group, which aims is the prevention and early diagnosis of breast cancer [1,3,6,12,19,23]. It is proved that up to 10% of malignant breast tumors are genetically determined and, perhaps, the most of molecular genetic studies in oncology are focused on breast cancer problems [10,13,14,16,17,24]. At the same time, despite the many advances in the prevention and diagnosis of this disease, the high levels of mortality are stably maintained. Mortality from breast cancer in the Altai region in 2013 was 28.1%ooo (in the Russian Federation in 2012 - 29.8%ooo) [5]. Thus, the problem of prevention of malignant tumors of the breast is not yet resolved and remains extremely relevant.

The genetic polymorphism of enzymes of synthesis and metabolism of estrogens can input into predisposition to breast cancer. The purpose of actual study was to analyze the associations of polymorphic loci CYP17/B1rs10556836, CYP1A 1rs1048943, CYP1A2rs762551, CYP19A1rs2470152 and CYP17A1rs743572 with risk of development of breast cancer in Russian residents of the Western-Siberian region of Russia. The rates of alleles and genotypes of the given loci were determined in sampling of women suffering with breast cancer (n = 670 females) and in control group (480 females without oncological diseases). The sub-groups of patients with breast cancer in pre-menopause--and post-menopause were analyzed separately. The border-line association of locus CYP17A1rs743572 is demonstrated with increasing of risk of breast cancer during pre-menopause (allele C: p = 0.04). Among the rest of polymorphic loci no association was detected.

The genetic polymorphism of enzymes of synthesis and metabolism of estrogens can input into predisposition to breast cancer. The purpose of actual study was to analyze the associations of polymorphic loci CYP171B1rs10556836, CYP1A1rs1048943, CYP1A2rs762551, CYP19A1rs2470152 and CYP17A1rs743572 with risk of development of breast cancer in Russian residents of the Western-Siberian region of Russia. The rates of alleles and genotypes of the given loci were determined in sampling of women suffering with breast cancer (n=670 females) and in control group (480 females without oncological diseases). The sub-groups of patients with breast cancer in pre-menopause and postmenopause were analyzed separately. The border-line association of locus CYP17A1rs743572 is demonstrated with increasing of risk of breast cancer during pre-menopause (allele C: p=0.04). Among the rest of polymorphic loci no association was detected.

e12560 Background: Breast cancer (BC) for more than 10 years is the most frequent cancer in females in the Altai territory of Russian Federation. The share of patients under 40 years old varies from 2.6% to 16.0%. Genetically dependent nature of BC in young female is scientifically confirmed fact. The aim of this study was to analyze characteristics of BRCA-associated and sporadic BC in fertile females. Methods: 161 female patients of fertile age (under 40 years old) with BC were examined. Clinical, morphological and genetic (BRCA1) factors were analyzed. BRCA1 mutation was revealed in 22 patients (139 patients did not have it). Results: 82.0% of patients with BRCA1 mutations had positive family cancer history. In this group BC was diagnosed more frequently at the age of 31-35 y.o. (40.9%), while in the group of sporadic cancer – at the age of 36-40 y.o. (58.2%). Pathomorphological forms of BC were analyzed and in both groups infiltrative forms of BC were the most frequent (95.5% and 91.4% correspondingly). I stage cases of BC were diagnosed more frequently the group of sporadic cancers than in the group of BRCA-associated cancers (23.0% and 4.5% correspondingly, P<0.05). Hormone status of the tumours was analyzed. BRCA-associated cancers were significantly more often ER and PR negative (87.5%, P<0.05). Hyperexpression of Her2neu was not revealed in this group. In the group of patients without BRCA mutation ER and PR negative tumours were also prevalent (60.5%, P<0.05). Hyperexpression of Her2neu (+++) was revealed in 6.9%. Triple negative cancers were prevalent in the both groups, while in the group of BRCA-associated cancers there were 91.7% of such tumours. The percentage of polyneoplasia in the group of patients with BRCA mutations was higher than in the group without them (12.0 and 1.0 correspondingly, P<0.05). Conclusions: In females of fertile age carriage of BRCA mutations in 82.0% connected with family cancer history. In the group of sporadic cancers I stage cases of BC are more frequent. In both groups hormone receptor negative and triple negative cancer are prevalent, but in the group of BRCA-associated cancers the percentage of such tomours and polyneoplasia are significantly higher.

e11047 Background: MPC represents the interest for their prognosis and more effective treatment. The objectives of our research was to investigate clinical and genetic characteristics of MPC among women with familial and sporadic BC. Methods: The research is based on data of 1407 Caucasian women with BC aged 20-79 years (555-familial BC, 852– sporadic BC), control group consisted of 1006 women without a history of cancer. In all groups were analyzed more than 100 phenomic and genotypic factors. Processing of the results was performed using modern methods of biomedical statistics. Statistically significant differences taken at p<0.05. Genotyping was carried out by real-time PCR using competitive Taq-Man probes or with allele-specific PCR using SYBR Green intercalating dye. Results: Specific weight of MPC in group of familial BC [18,0% (14,74-21,26] was higher than in group of sporadic BC [2,0% (1,04-2,96)]. Among women with familial BC with MPC premenopause status met more rapidly [10,1 (4,06-16,14)] than in the group of sporadic BC with MPC [5,0 (1,26-8,74)]. Specific weight of BRCA-negative cases and FGFR-mutations were higher in familial group with MPC than in the group of sporadic BC with MPC [68,7% (59,38-78,02) against 40,0% (18,10-61,90); 3,0% (0,42-6,42) against 35,0% (13,66-56,34)]. Patients with triple negative and HER2neu positive BC met more frequently in familial group with MPC than in the group of sporadic BC with MPC. Reproductive factors such as obesity, aborts and others also had significance. Conclusions: Clinical and genetic characteristics of MPC in group of familial BC have different characters as against as group of sporadic BC.

Рак молочной железы – одно из самых распространенных онкологических заболеваний у женщин. Изучена роль аллельных вариантов генов фолатного цикла – C677T и A1298C гена MTHFR, C1420T гена SHMT1 и G1258A гена MTHFD – в формировании предрасположенности к этому виду рака. Определены частоты встречаемости аллелей и генотипов указанных однонуклеотидных полиморфизмов в контрольной группе (810 женщин) и в группе больных со спорадической формой рака молочной железы (850 женщин). Ни один из полиморфных локусов не показал статистически значимой ассоциации с риском рака молочной железы. С целью увеличения статистической мощности исследования проведен мета-анализ, в который вошли как опубликованные данные, так и результаты, полученные в нашей работе. В результате мета-анализа не обнаружено статистически значимой ассоциации ни одного из изучаемых полиморфных локусов с риском рака молочной железы.

Breast cancer is one of the most widely distributed cancers in women. We investigated the role of allele variants in the folate metabolizing genes MTHFR (C677T and A1298C alleles), SHMT1 (C1420T allele), and MTHFD (G1258A allele) as a possible factor in predisposition to breast cancer. We determined allele and genotype frequencies of single nucleotide polymorphisms (SNPs) in the case (850 women with sporadic form of breast cancer) and control (810 healthy women) groups. None of the polymorphisms were significantly associated with breast cancer risk. To increase the statistical power of our study, we conducted a meta-analysis which included published genotype data and the results of our work. The meta-analysis revealed no significant association between the studied SNPs and breast cancer risks either.

Abstract Background: Breast cancer (BC) is the most prevalent cause of mortality from cancer in women aged 40-69 years in Russian Federation. There are results of clinical researches about triple negative BC [ER(-); PR(-); HER2/neu (-)]. Materials and Methods: The register consisted of 1428 Caucasian women with BC aged 20-79 years (756 — familial and 672 — sporadic BC), control group composed 1581 Caucasian women aged 19-84 years without of cancer. The questioning including data of pheno- and genotype. BRCA or other mutations were performed to all patients. The researching morphological traits of tumor were histological type, estrogen receptor (ER), progesterone receptor (PR) and HER2/neu. Results: Triple negative BC was found out by 21 BRCA positive patients, 32 BRCA negative patients and 27 patients with sporadic BC. Some of reproductive and clinical factors differed in two groups: triple negative and non-triple negative BC. Among triple negative BC patients, women with sporadic BC were older and had clinical stage higher. Specific gravity of rare tumors was higher by patients with BRCA mutations. Conclusion: The women with BC can be divided into two groups: having triple negative phenotype and all the rest. Considering these factors let us prognosticate progress notes and form an individual plan of special treatment. Citation Information: Cancer Prev Res 2010;3(12 Suppl):B72.

The frequencies of the polymorphic gene variants MnSOD Ala9Val, GPX1 Pro198Leu, and GSTP1 Ile105 Val were estimated in female residents of Altai krai with breast cancer. The frequency distributions of the genotypes for all genes studied in both patients and control subjects fit the Hardy-Weinberg equilibrium. The estimated frequencies of the genotypes for the studied genes in the control group did not differ from those earlier reported for Caucasoid women living in Europe. The T(rs1050450) allele of the GPX1 gene was demonstrated to protect against sporadic breast cancer (OR = 0.74 (95% CI = 0.58-0.94), p = 0.012). Carriers of the genotype combination MnSOD CC + GPX1 CC were found to have a 1.6 times higher risk of sporadic breast cancer compared to the control group (OR = 1.59 (1.05-2.41), p = 0.0258). The polymorphic loci GSTP1 (rs1695) and MnSOD (rs4880) were not found to be significantly associated with the risk of familial or sporadic breast cancer.

e12064 Background: It is known that the presence of syndrome operated breast significantly increases risk of cancer in this organ. However, not all women, who had a history of breast surgery at the non-neoplastic diseases, develops breast cancer. The objectives of our study was to reliably identify significant factors influencing the development of breast cancer among women with the syndrome of the operated breast. Methods: The study is based on data on 505 women in history, who had a surgical trauma of breast over the non–neoplastic pathologies. In 73 of them (14.5%), subsequently, detected breast cancer. In both groups were analyzed more than 40 endo- and exogeneous factors. Processing of the results was performed using modern methods of biomedical statistics, the definition of relative risk (RR). Statistically significant differences taken at p < 0.05. Results: Among the endogenous endocrine factors, high relative risk (RR = 2.82 [1.59-4.98]) detected in women with the presence of the factor of obesity...

e22223 Background: Hereditary breast carcinomas that are attributable to BRCA1 mutations have their own morphological and immunohistochemical characteristics. This study was aimed to analyze the level of expression of steroids (estrogen and progesterone) and HER2-neu receptors in BRCA1 associated breast cancer. Methods: DNA patterns from 264 patients with hereditary breast cancers (breast cancer diagnosed at the age under 40; bilateral breast cancer; combination of breast and ovarian cancers; 2 and more breast cancers in blood relatives). All the patients were residents of the Altai Territory. BRCA1 gene mutations were registered in 34 patients (12.9%): 5382insC gene mutation - in 28 patients; 300A/C - in 2 patients; 4153del - in 3 patients; 185del - in 1 patient. The frequency of the BRCA1 5382insC allele mutation was 7.3; 300A/C - 0.52; 4153del - 0.26; 185del - 0.83. Immunohistochemical characteristics of BRCA1-associated breast tumors tissue from these patients were investigated. Results: 32 BRCA1-associated breast carcinomas were estrogen receptor- negative; 1 - week positive (H-score 50–100); 1 - moderate positive (H- score 100–200). 33 BRCA1-associated breast carcinomas were progesterone receptor- negative; 1 - positive (H-score 200 and more). HER2-negative were 31 BRCA1-associated breast carcinomas; 2 were week positive (HER2-neu +); 1 - was moderate positive (HER2-neu ++). Conclusion: BRCA1-associated beast carcinomas have been found to be more frequently estrogen receptor-, progesterone receptor-, and HER2- negative. These data show that hereditary breast cancer associated with BRCA1 gene mutations poses poor prognosis. No significant financial relationships to disclose.