Objective of the study is to develop and validate a predictive model for the prognosis of the probability of detection of targetable alterations using comprehensive genomic profi ling (CGP) in patients with metastatic breast cancer (BC).
Materials and Methods. Data of 28 patients with metastatic breast cancer, who had undergone comprehensive genomic profiling (CGP) using targeted next generation sequencing (NGS) and of a comparison cohort without comprehensive genomic profi ling (CGP) — 140 patients were included in the model. The predictive model was developed using decision tree approach with integration of a-priori data. The model was validated using k-fold cross-validation, and the quality assess ment was carried out using AUC ROC. Bootstrap analysis was performed to confi rm the stability of the results.
Results. Potentially targetable alterations were revealed in 67,9% of patients, of whom 35,7% corresponded to ESCAT I/II levels. The model demonstrated high prediction accuracy (AUC ROC = 0,78). The phenotype of breast cancer, number of revisions of biomaterial and the type of material (operative or biopsy) were the key predictors for the detection of alterations. The results of bootstrap analysis confirmed the stability of the model.
Conclusion. The developed predictive model allows for highly accurate prediction of the probability of detecting targetable mutations in patients with metastatic breast cancer. The use of the model contributed to the optimization of molecular testing and enhances the effectiveness of personalized therapy. Further studies with external validation are required to confirm the results.
Keywords: metastatic breast cancer, comprehensive genomic profi ling (CGP), targetable mutations, predictive model, next generation sequencing
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Introduction. Breast cancer in women under 25 years of age is rare, but it is marked by high aggressiveness and particular biology, which require individualized approach to diagnosis and treatment. Current research indicates a significant increase in breast cancer incidence among young women, that is associated with an earlier onset of the disease, genetic predisposition and a high rate of mutations in BRCA 1/2 gene. The unique clinical and morphological characteristics of this age group emphasize the need for in-depth study of this issue to develop effective methods of prevention, therapy and improving prognosis.
Objective of the study is to determine the clinical, morphological and biological characteristics of breast cancer in patients under 25 years of age.
Materials and Methods. Case medical histories of patients with breast cancer under 25 years of age were analyzed in a multicenter retrospective study carried out for the period from 2008 to 2020. These patients underwent treatment in Breast Tumor Division of the Department of Breast Cancer of Federal State Budgetary Institution “N. N. Blokhin National Medical Research Center of Oncology” of the Ministry of Healthcare of the Russian Federation (Moscow), at State Autonomous Healthcare Institution Republican Clinical Oncologic Dispensary of the Ministry of Healthcare of the Republic of Bashkor tostan (Ufa), Federal State Budgetary Educational Institution of Higher Education Tyumen State Medical University of the Ministry of Healthcare of the Russian Federation (Tyumen), Regional State Budgetary Healthcare Institution “Krasnoyarsk Regional Clinical Oncological Dispensary named after A. I. Kryzhanovskiy” of the Ministry of Healthcare of the Russian Federation. The clinical and morphological intricacies of breast cancer in this group of patients were assessed.
Results. The study comprised 65 patients aged 18 to 25 years, the mean age was 21,5 years. Stages IIA (26,1 %) and IIB (20 %) were the most frequently identifi ed in our study. By histologic subtype, invasive ductal carcinoma prevailed in 86,1 % of patients. Of the molecular biologic subtypes luminal B Her2-negative subtype predominated in 30,7 % of pa tients and triple negative subtype — in 35,3 % of patients. By the grade of malignancy G2 cancer (72,3 %) was the most common. Based on mammography results, the average size of the tumor node was 3,2 cm and regional lymph node involvement was found in 58,5 % of patients. Molecular genetic testing was performed in 55,3 % of patients, in 38,8 % of whom pathogenic mutations were identifi ed: in BRCA1 gene — in 27,7 %, in BRCA2 gene — in 8,3 %, in CHEK 2 — in 2,7 %. Mutation 5382insC in BRCA1 was the most common.
Conclusions. The results obtained in the study emphasize the need for a comprehensive and multidisciplinary approach to the treatment of young breast cancer patients, as well as the importance of further research with a view to a more profound investigation of molecular biological mechanisms, that underlie aggressive disease course at such an early age. Particular consideration should be given to the development of standardized diagnostic, treatment and monitoring protocols for this age group, which will allow to enhance the effi cacy of therapeutic measures and improve long-term prognosis.
Keywords: breast cancer in young women under 25 years of age, clinical and morphological characteristics, biological intricacies of tumors
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Objective of the study is to conduct a systematic analysis of the data available in current literature on the effect of prostheses, previously emplaced for aesthetic purposes, in complicating diagnostics and treatment of breast cancer, since the placement of implants and prior surgical intervention on the breast make a number of changes in the anatomy of the organ.
Materials and Methods. The review comprises the data of foreign and Russian scholarly articles found in PubMed on the subject published over the past 10 years.
Results. Published meta-analyses demonstrated no increase in breast cancer incidence rates after the placement of silicone and saline implants. To date, the “gold standard” for the diagnosis of breast cancer has been established which includes diagnostic ultrasound of the breast, mammography and targeted fi ne-needle biopsy of the mass. The use of MRI examination instead of mammography has become the recommended standard for patients with implants, since mammography involves direct mechanical impact on the breast, which can lead to rupture of the implant capsule, its dislocation and other adverse events.
Conclusion. In case of the established diagnosis of breast cancer the medical history of augmentation mammoplasty requires an individualized approach to diagnosis and treatment.
Keywords: augmentation, mammoplasty, breast cancer, mammography, reconstructive plastic surgery
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Objective of the study is to carry out a systematic analysis of the literature devoted to perivascular epithelioid cell tumors (PEComas), to present the current view on pathogenesis, diagnosis and treatment of this rare type of tumor.
Materials and Methods. The review comprises the data of foreign and Russian academic articles, found in PubMed on the subject, published over the past 10 years.
Results. Perivascular epithelioid cell tumors (PEComas) are the tumors of mesenchymal nature, that consist of perivas cular epithelioid cells. Perivascular epithelioid cell tumors (PEComas) classifi cation is based on their morphological and immunohistochemical characteristics, such as an expression of melanocyte markers (HMB–45, Melan-A, MiTF) and muscle markers (SMA, desmin, myosin), as well as of vimentin, estrogen receptors and the others.
Conclusion. Further research, that can contribute to develop the best approach to the treatment of this pathology is required.
Keywords: perivascular epithelioid cell tumor (PEComa), morphology, diagnosis, treatment
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Objective of the study. To evaluate the actual clinical practice of BRCA-associated ovarian cancer treatment in Russia.
Materials and Methods. The OVATAR study was conducted from 2014 to 2018 in 29 hospitals in Russia. The aim of the study was to evaluate treatment approaches of ovarian cancer (OC). The study included patients of 18 years and older with newly diagnosed serous and endometrioid cancer of the ovary, fallopian tube, and peritoneum. The drug treatment regimens, the chemotherapy effect, the volume and timing of surgical treatment were evaluated.
Results. The study included 500 patients, and 496 (99.2%) patients underwent BRCA1/2 gene mutation detection. The frequency of mutations in the BRCA1/2 genes in the Russian patient population was 28.4% (n = 141/496). In BRCA-associated OC, surgery was performed in 77.3% (n = 109/141), primary cytoreductive surgery was performed in 94.5% (n = 03/109): complete in 48.6% (n = 53/109), optimal in 11% (n = 12/109), suboptimal in 40.4% (n = 44/109). Preoperative neoadjuvant chemotherapy was performed in 23.4% (n = 33/141), of which 9% (n = 3/33) had a complete response, 72.7% (n = 24/33) had a partial response, and 18.3% (n = 6/33) had stabilization. Interval cytoreduction was performed in 18.2% (n = 6/33), and no surgical treatment was performed in 81.8% (n = 27/33). Complete interval cytoreductive surgery was performed in 50% (n = 3/6), optimal in 33.3% (n = 2/6) and suboptimal in 16.7% of cases (n = 1/6). 98.6% of patients (n = 139/141) received chemotherapy, 96.4% (n = 134/139) received multicomponent chemotherapy. Platinum based chemotherapy was performed in 99.3% (n = 138/139), non-platinum chemotherapy in 0.7% (n = 1/139). Olaparib maintenance therapy was performed in 12.8% (n = 18/141).
Conclusion. The results of the study made it possible to evaluate the treatment of ovarian cancer in real clinical practice in Russia. It has also identifi ed the disadvantages in therapeutic approaches.
Keywords: ovarian cancer, mutations in BRCA1/2 genes, cytoreductive surgery, chemotherapy, maintenance therapy
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Introduction. Malignant trophoblastic tumors are rare, but highly aggressive neoplasms, associated with pregnancy. Although most patients with this nosology are successfully treated with chemotherapy, tumors of extremely high risk (FIGO score of 12 or higher) are characterized by poorer survival rates due to the high incidence of early mortality, as well as to the development of multiple drug resistance, which requires the search for the new treatment approaches.
Objective is to analyze the experience of treating patients with malignant trophoblastic tumors of extremely high risk of drug resistance in the Russian population.
Materials and Methods. A retrospective analysis of 44 patients with malignant trophoblastic tumors of extremely high risk of drug resistance who had undergone treatment at Federal State Budgetary Institution “N. N. Blokhin National Medical Research Center of Oncology” of the Ministry of Healthcare of the Russian Federation for the period from 2005 to 2023 was carried out. The primary endpoint was 1-year progression-free survival. Secondary endpoints of the study were 1-year overall survival, complete tumor regression rate, toxicity and safety of the treatment. Statistical processing and analysis of the data obtained were performed using the MedCalc software.
Results. With a median follow-up of 60,4 months, the 1-year progression-free survival rate of extremely high — risk patients was 78,6 %, and the 1-year overall survival rate was 93,3 %. Complete tumor regression was achieved in 81,8 % of patients after the first line of chemotherapy, and this indicator differed depending on the pre-treatment, making up 64,2 % and 90 % in the subgroups with or without prior treatment, respectively (p = 0,039). All patients were diagnosed with stage III or IV of the disease. Grade 3–4 toxicity was observed in 63,6 % of patients, the majority of which were hematological adverse events.
Conclusion. Malignant trophoblastic tumors of extremely high risk of drug resistance, which have the worst cure rates, are an extremely rare pathology even in the practice of large expert centers. To improve the long-term results of treatment for this cohort of patients, it is necessary to explore new approaches, including, in addition to chemotherapy, targeted therapy and immunotherapy.
Keywords: malignant trophoblastic tumors, choriocarcinoma, extremely high risk of drug resistance, stabilization chemotherapy
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Feasibility. A pelvic exenteration is one of the treatment options for locally advanced cervical cancer with continuous growth or recurrence after chemoradiation therapy. In a number of cases, the extent or complications of tumor process require more extensive surgical intervention involving resection of the pelvic lateral wall structures which is presented in the case series below.
Materials and Methods. 5 total pelvic exenterations based on LEER technique (Laterally extended endopelvic resection, or resection of the pelvic lateral wall) for complicated course of squamous cell cervical cancer after chemoradiation treatment were performed at the Department of Oncology № 4 of Oncologic Center № 1 of the State Budgetary Healthcare Institution “City Clinical Hospital named after S.S.Yudin of Moscow Department of Healthcare” for the period from February 2020 to February 2024. The age of patients ranged from 38 to 55 years. The body mass index (BMI) of the patients varied from 16,5 to 24,8 kg/m2. All women underwent radiation therapy, from 1 to 4 lines of drug therapy, 2 patients had previously undergone surgery in the extent of radical hysterectomy and trachelectomy, respectively. In all women the intervention was a “salvage” surgery due to the presence of life-threatening complications caused by tumor disintegration.
Results. The duration of operations ranged from 300 to 500 minutes (median — 410). The volume of blood loss varied from 300 to 2000 ml (median — 1000 ml). Radical intervention (R0) was achieved in 4 patients, in 1 case a positive circumferential resection margin (R1) was identified. The average length of hospital stay after surgery was 19 days (14–28), the length of stay in the intensive care unit ranged from 1 to 4 days. There was no in-hospital mortality, however, 1 patient died 2 months after surgery due to the development of lung abscess. The quality of life of the other 4 patients improved after surgery owing to the elimination of the manifestations of tumor process. The maximum duration of relapse — free period is currently 21 months.
Conclusion. Resection of pelvic lateral wall is an important procedure of a pelvic exenteration for locally advanced cervical cancer and it can be performed with good immediate results, however, the oncological outcomes of this technique require further investigation.
Keywords: cervical cancer, pelvic exenteration, pelvic lateral wall resection, laterally extended endopelvic resection
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Borderline ovarian tumors are neoplasms with low malignancy potential, which are a group of neoplasms that have characteristics of both benign and malignant tumors. They account for 15–20 % of all ovarian epithelial neoplasms. Unlike ovarian carcinoma, this pathology occurs mainly in young women. The most common histotypes include serous types (53 %). Serous borderline ovarian tumor (SBOT) is a pathology which can manifest and even progress during pregnancy that causes signifi cant clinical and diagnostic challenges.
Objective of the study. To present a clinical case of a 26-year-old woman with a recurrence of serous borderline ovarian tumor during pregnancy after initial organ-preserving surgical treatment.
Materials and Methods. The publication describes the clinical case of a 26-year-old patient with a recurrence of serous borderline ovarian tumor during her current pregnancy, who underwent organ-preserving surgical treatment after her first emergency spontaneous labor.
Results. A 26-year-old female patient with a recurrence of serous borderline tumor in a single ovary underwent repeat minimally invasive surgery on the fi fth day postpartum after emergency spontaneous labor.
Conclusion. In this clinical case we observed a recurrence of serous borderline ovarian tumor in a patient during pregnancy. Careful monitoring of women of reproductive age after undergoing primary organ-preserving surgical treatment is of signifi cant importance. Despite the potential risks, associated with disease progression and surgical intervention during pregnancy, timely diagnosis and adequate management strategy can signifi cantly improve the prognosis for both mother and fetus. This case illustrates the need for multidisciplinary approach, involving obstetricians, gynecologists and oncologists to ensure optimal management of patients with such diseases. Future studies should focus on the development of protocols for the management of patients with recurrent serous borderline ovarian tumor during pregnancy to provide for the health of mother and fetus, as well as for the optimization of treatment outcomes.
Keywords: serous borderline ovarian tumor, recurrence, pregnancy, conservative surgical treatment, safety of mother and fetus
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Objective of the study is to carry out a systematic analysis of the evidence, accumulated in current literature to assess the modifying effect of combined oral contraceptives on ovarian and breast carcinogenesis.
Materials and Methods. The review includes the data of foreign and Russian academic articles found in PubMed on the subject, published over the past 10 years.
Results. It was established, that the overall probability of developing cancer in the population does not change with the use of oral contraceptives (OCs). An increased risk of developing breast cancer with the use of oral contraceptives (OCs) is not confi rmed in the literature; results vary from no increase in risk to an increase of 20–30 %. And this risk appears to be temporary, limited to recent or current regular use of oral contraceptives (OCs). Moreover, evidence indicates that continuous and long-term use of oral contraceptives (OCs) may reduce the risk of ovarian cancer. Although the studies do not provide unambiguous confi rmation of an increased risk with the use of oral contraceptives (OCs) in women with a family history of cancer or carriers of BRCA gene mutations, a personalized approach is needed for clinical decision making.
Conclusion. It is necessary to continue further research in this regard.
Keywords: combined contraceptives, breast cancer, ovarian cancer
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