We studied the effect of functionally significant polymorphic markers of the ESR1 gene on the risk of breast cancer, tamoxifen resistance, and survival of patients with this type of cancer. The study included 239 primary breast cancer patients without distant metastases. The analysis of genotype frequency distribution for the studied ESR1 gene polymorphic markers showed the association of the rs2228480 and rs2234693 markers with tamoxifen resistance in the group of patients with luminal B type breast cancer. An association of these two polymorphic markers with the risk of tumor development was also revealed; for rs2234693 polymorphic marker, a relationship with the survival of patients was also showed.

Рак молочной железы (РМЖ), является заболеванием, в патогенезе которого принимают участие множество различных факторов, в том числе и генетические, а именно однонуклеотидные замены в генах биотрансформации ксенобиотиков и одноуглеродного обмена. В частности, изменения в генах GSTP1 и MTHFR, влияют на риск развития РМЖ, и могу приводить к нечувствительности опухоли к препаратам антрациклинового ряда, например, к доксорубицину. Целью данной работы являлось изучение влияния полиморфных маркёров rs1695 гена GSTP1 и rs1801133 и rs1801131 гена MTHFR на риск развития РМЖ и чувствительность к терапии доксорубицином. Методы. В работу было включено 239 больных РМЖ из Москвы и Московской области, для которых был установлен диагноз и клинические патоморфологические особенности, включая иммуногистологический статус опухоли. В качестве популяционного контроля использовали сопоставимую по возрасту выборку онкологически здоровых женщин (n = 200). Определение генотипов полиморфных маркёров rs1695, rs1801133, rs1801131 проводилось методом анализа кривых плавления ДНК с помощью ПЦР «в реальном времени» на амплификаторе “Real-time CFX96 Touch” (Bio-Rad, США) с использованием готовой смеси для ПЦР qPCRmix-HS (Евроген, Россия). Результаты. Выявлены статистически значимые ассоциации полиморфного маркёра rs1695 гена GSTP1 и rs1801133 гена MTHFR с риском развития РМЖ (OR = 1,15, CI95% = 1,14-2,00, р = 0,0114 и OR = 1,57, CI95% = 1,19-2,08, р = 0,0023, соответственно). При анализе ассоциации изученных полиморфных маркёров с эффективностью ответа на химиотерапию доксорубицином было показано, что в группе больных с «плохим» ответом на химиотерапию выявлялось значимое увеличение частоты аллеля Val полиморфного маркёра rs1695 гена GSTP1 и аллеля С полиморфного маркёра rs1801133 гена MTHFR. Нами также выявлена статистически значимая ассоциация полиморфного маркёра rs1801133 гена MTHFR (р = 0,0397) с выживаемостью больных с РМЖ. Заключение. Полученные нами результаты дополняют информацию о причинах возникновения резистентности к доксорубицину, и дают возможность сформировать группы риска с негативным ответом на данную химиотерапию. Background. Breast cancer (BC) is a multifactorial disease. Different factors contribute to the BC pathogenesis, including genetic factors, such as single-nucleotide variations in genes of xenobiotic biotransformation and one-carbon metabolism. Specifically, changes in GSTP1 and MTHFR genes influence the risk of BC and may result in a decreased response of the tumor to anthracycline drugs, such as doxorubicin. Aim. The aim of this study was to evaluate the effect of polymorphic markers, rs1695 of the GSTP1 gene and rs1801133 and rs1801131 of the MTHFR gene, on the risk of BC and sensitivity to the doxorubicin therapy. Methods. The study included 239 BC patients from Moscow and the Moscow Region with established clinical pathomorphological features of the tumor, including the immune histological status. The population control group consisted of age-matched women without an oncological disease (n = 200). Genotypes of rs1695, rs1801133, and rs1801131 polymorphic markers were determined by analysis of DNA melting curves with real-time PCR performed on a Real-time CFX96 Touch amplifier (Bio-Rad, USA) with a qPCRmix-HS ready-to-use PCR kit (Eurogen, Russia). Results. The study showed statistically significant associations of the GSTP1 gene rs1695 polymorphic marker and the MTHFR gene rs1801133 polymorphic marker with the risk of BC (OR = 1.15, CI95% = 1.14-2.00; p = 0.0114 and OR = 1.57, CI95% = 1.19-2.08; p = 0.0023, respectively). The study of polymorphic marker association with response to the doxorubicin chemotherapy showed that in the group of patients with a poor response to chemotherapy, frequencies of the Val allele in the GSTP1 gene rs1695 polymorphic marker and the C allele in the MTHFR gene rs1801133 polymorphic marker were significantly increased. Also, the MTHFR gene rs1801133 polymorphic marker (p = 0.0397) was significantly associated with survival of BC patients. Conclusion. The results of this study supplemented information about causes for resistance to doxorubicin and will allow isolating groups at risk with a negative response to the doxorubicin chemotherapy.

Breast cancer ranks first among all cancers in women in the world. Despite the great achievements of complex treatment, there is a category of patients is not sensitive to drug therapy. One of the reasons for the lack of effect of drug therapy in patients with breast cancer may be multi-drug resistance. The article presents the experience of the use of the marker of multidrug resistance Pgp, as a predictive factor for the effectiveness of the proposed chemotherapy.

Currently, there is a marked tendency towards improvement of early detection of breast cancer that allows patients at extremely low risk for developing recurrent disease to be identified. Therefore, it is necessary to search for biological markers of unfavorable prognosis for patients with hormone-dependent breast cancer. In order to introduce these markers into routine clinical practice, they should be validated in welldesigned clinical studies, provide additional predictive information and be easily reproducible. The standard immunohistochemical parameters (estrogen and progesterone receptors and Ki67 cell proliferation index) can be served as these markers. However, the dynamic changes in these parameters during hormone therapyrather than their initial expression levels in the tumor are of great significance for the individualized hormone therapy.

Today one of the discussed issues of surgical treatment of primary operable breast cancer is the appropriateness of performing lymphadenectomy in different volumes. Conducting mammographic screening increases the proportion of patients with minimal breast cancer in which a standard lymphadenectomy in the majority of cases is excessive and crippling procedure. We have analyzed the results of several multicenter studies, which in our opinion have changed the attitude of clinicians to the advisability and scope of lymphadenectomy.

The article presents an overview of the literature about breast sarcomas (nonepithelial malignances). Primary sarcomas are extremely rare, with less than 1 % of all malignant tumors of the breast. Breast carcinomas cause an increased interest of the scientists due to their unique clinical and pathological features and unpredictable prognosis.