Аннотация. Синдром поликистозных яичников (СПКЯ)-одна из наиболее частых форм эндокринопатий. Несмотря на высокую частоту СПКЯ и многолетнюю историю изучения, вопросы этиологии, патогенеза, диагностики и лечения синдрома до сих пор являются наиболее дискутабельными. В последние годы все большее внимание ученых привлекает вопрос о вкладе гиперинсулинемии в развитие СПКЯ. Известно, что в 50-70% случаев СПКЯ сочетается с ожирением, гиперинсулинемии и изменениями липидного спектра крови, что повышает риск развития сердечнососудистых заболеваний, сахарного диабета 2 типа и приводит к снижению средней продолжительности жизни. Многие исследователи указывают на генетическое детерминирование метаболических нарушений при СПКЯ, проявление которых усугубляется при наличии избыточной массы тела. Современный этап в изучении патогенеза СПКЯ характеризуется углубленным исследованием метаболических нарушений: инсулинрезистентности, гиперинсулинемии, ожирения, гипергликемии, дислипидемии, системного воспаления, изучением их опосредованного воздействия на патологический процесс в яичниках, и связанных с ними таких заболеваний, как инсулинонезависимый сахарный диабет и сердечно-сосудистые заболевания. Этим можно объяснить поиск новой специфической диагностики, чтобы определить, какие из маркеров могут использоваться в повседневной практике в качестве предикторов метаболического и сердечно-сосудистого риска у пациенток с СПКЯ.
Relevance. Endocrine therapy is the standard treatment for women with ER-positive breast cancer. The clinical response to Tamoxifen is variable. Approximately 30 % of patients with breast cancer will have a recurrence of the disease within 15 years after treatment, despite ongoing endocrine therapy. This article presents the results of a prospective pharmacogenetic cohort study. The study was conducted in 2018–2019. Aim. To analyze adverse drug reactions to Tamoxifen in the adjuvant regimen in breast cancer patients in relation to the carriage of genetic polymorphisms of genes encoding cytochrome P450 enzymes and drug transporter proteins and to build predictive models based on them. A comparative analysis of the relationship between genetic and non-genetic determinants with adverse events on tamoxifen therapy allowed us to build predictive models of their development. Materials and Methods. The study involved 120 women with pre- and postmenopausal breast cancer who underwent genetic testing for CYP and Pg enzyme gene polymorphisms. Entry criteria: a histologically confirmed diagnosis of breast cancer, taking Tamoxifen at the recommended doses, establishing a diagnosis not earlier than 2007, and obtaining informed voluntary consent to participate in the study. Allelic variants were determined using real-time polymerase chain reaction in the Research Institute for Molecular and Personalized Medicine of the Russian Medical Academy of Continuous Professional Education of the Ministry of Healthcare of the Russian Federation. Results. An associative analysis showed their association with the development of adverse drug reactions (ADR) to Tamoxifen, indicating the clinical significance of different genetic polymorphisms of CYP2D6, CYP3A5, CYP2C9 and ABCB1. The complex associative analysis performed using mathematical modeling made it possible to build predictive risk models for the development of such ADR, such as hot flashes, dyspepsia, bone pain, and asthenia. The resulting regression models were statistically significant (p < 0,001) and demonstrated high diagnostic efficiency. This allows them to be implemented in clinical practice. Conclusion. Thus, models that include both genetic and non-genetic determinants of response may further improve the prediction of individual response to tamoxifen
Background. One of the main stages of the treatment of breast cancer (BC) is endocrine therapy with tamoxifen or aromatase inhibitors. Five years of adjuvant tamoxifen therapy reduces the risk of disease recurrence by 39%. Tamoxifen was approved by the U.S. Food and Drug Administration in 1977 as a treatment for ER-positive BC. However, sometime after the start of tamoxifen's wide use, reports have been published on its long-term adverse effects. Most common were hot flashes, gynecological symptoms (vaginal dryness, vaginal discharge), depression, forgetfulness, sleep changes, weight gain, and decreased libido. However, more serious adverse events such as venous thromboembolic disease and endometrial hyperplasia or cancer are the most clinically significant. The article presents the results of a retrospective population-based study on assessing hyperplastic processes of the endometrium (HPE) in patients with breast cancer during TAM therapy, conducted in 2017, approved by the Ethics Committee of the Scientific Research of the Russian Medical Academy of Continuing Professional Education. Aim. To identify clinical factors that may increase the risk of HPE during tamoxifen therapy in patients with a history of breast cancer living in the Moscow region. Materials and methods. We retrospectively reviewed 230 case histories of patients with breast cancer. Of these, 120 patients who received TAM therapy had the following HPE risk factors: average age, menopausal status, body mass index, and duration of TAM therapy. Results. It was found that patients with HPE taking TAM were older (p=0.017), more likely to be postmenopausal (p=0.035), overweight (p=0.023), and received TAM for a longer period (p=0.028) than patients without HPE. Conclusion. The data obtained indicate the need for continuous monitoring by gynecologists of patients with breast cancer taking tamoxifen, paying particular attention to women from high-risk groups, namely older postmenopausal women with high body mass index receiving TAM for more than 1.52 years.
Objectives The present study investigated the analysis of adverse drug reactions (ADRs) to Tamoxifen (TAM) in breast cancer patients in relation to the carriage of genetic polymorphisms of genes encoding enzymes of CYP system and transporters of P-glycoprotein (Pg) and predictive models based on it. Methods 120 women with breast cancer taking adjuvant TAM were examined for the gene polymorphisms such as CYP2D6*4, CYP3A5*3, CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*3 and ABCB1 (C3435T). Allelic variants were determined using the real-time polymerase chain reaction method. The research material was double sampling of buccal epithelium. Medical history data and extracts from case histories were used as sources of medical information, on the basis of which questionnaires specially created by us were filled out. Results An associative analysis showed association with the development of ADRs to tamoxifen indicating their clinical significance from different genetic polymorphisms of CYP2D6, CYP3A5, CYP2C9 and ABCB1. The complex associative analysis performed using mathematical modeling made it possible to build predictive risk models for the development of ADRs such as hot flashes, dyspepsia, bone pain, and asthenia. Conclusions Models that include both genetic and non-genetic determinants of ADRs of TAM may further improve the prediction of individual response to tamoxifen.
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