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Tumors of female reproductive system

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Vol 18, No 2 (2022)
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https://doi.org/10.17650/1994-4098-2022-18-2

MAMMOLOGY. ORIGINAL ARTICLE

14-20 869
Abstract

Background. Comprehensive treatment of breast cancer includes surgery, radiation therapy and systemic treatment. Radiation therapy plays an integral role in the treatment of early breast cancer. The appointment of a targeted dose of radiation to the bed of the primary tumor reduces the risk of local recurrence.

Objective: to evaluate the effectiveness of intraoperative radiation therapy in the treatment of early breast cancer.

Materials and methods. A retrospective study was conducted on the basis of the St. Petersburg City Clinical Oncology Center. Patients with organ-preserving surgery and intraoperative radiation therapy were selected. Of the 352 patients, 273 patients met the inclusion/non-inclusion criteria. Inclusion criteria were verified breast cancer, clinical stage I–IIA, tumor size no more than 3 cm, absence of visible axillary lymph nodes and monocentric nature of tumor growth. All patients underwent sectoral resection of the mammary gland with a biopsy of the sentinel lymph nodes and intraoperative radiation therapy.

Results. The mean age of the patients was 59 years. For 273 patients, the median follow-up was 59.1 months. During this period, 18 (6.6 %) local recurrences of the disease were noted, of which 7 (39 %) patients with luminal A, 6 (33 %) patients with luminal B, 1 (6 %) patient with luminal B HER2/neu 3+, and 4 (22 %) patients with triple negative breast cancer. Within 3 years of follow-up, recurrence-free survival was 98.5 %, within 5 years – 96.4 %.

Conclusion. The use of intraoperative radiation therapy for early breast cancer is an effective and safe treatment method. 

21-28 274
Abstract

To identify the features of breast cancer metastases and assess stress after reconstructive operations, young patients were examined, surveyed for HADS and determined cortisol levels. It has been shown that the appearance of metastases can be influenced by the level of anxiety and depression. Performing breast reconstruction operations by improving the psycho-emotional state reduces the risk of metastasis. 

29-39 442
Abstract

Background. It is suggested that defects in BRCA1 / 2 genes contribute to a high mutational load and high immunogenicity, which modulates immune microenvironment. At the same time, it was shown that BRCA1 / 2-associated breast cancer tumors do not belong to the category of immunoactive ones. These tumors have low expression of immune response genes and exhibit an immunosuppressive type of microenvironment. This indicates the need of antitumor immune response modulation and maintaining of the optimal balance of tumor CD4/CD8 T-lymphocytes ratio. In addition, there is evidence of the additional evaluation of TP53 mutation in these tumors and disruption of the cell death process, which can also be a factor of resistance to therapy, including PARP inhibitors, and serve as a therapeutic target.

Materials and methods. The prospective study included 20 patients with BRCA1-associated breast cancer. BRCA1 / 2 mutations (BRCA1 185delAG, 4153delA, 5382insC, 3819delGTAAA, 3875delGTCT, 300T>G, 2080delA, BRCA2 6174delT) were detected in by real-time polymerase chain reaction. Immunohistochemical study was performed on paraffin embedded tissue blocks by an automated method on a ThermoScentific immunohistotainer using monoclonal antibodies. The expression of markers of tumor-infiltrating CD4+ and CD8+ T-lymphocytes, markers of macrophages (CD68, CD163), apoptosis (Bcl-2, p53), cell adhesion markers (E-cadherin, β-catenin) in breast cancer in carriers of BRCA1 mutations was assessed.

Results. High CD4/CD8 ratio, which characterizes immunosuppressive microenvironment, occurred in 75 % of cases. BRCA1 5382insC mutation is associated with high level of CD4+ TILs (p˂0.05), G2 is associated with a low CD4/CD8 ratio (p = 0.039) and a high level of CD163 (p = 0.02, AUC = 0.739); T1 correlates with high levels of CD8+ TILs (p = 0.038) and high levels of CD163 (p = 0.033). High Ki-67 is associated with a lack of Bcl-2 expression (p = 0.04) and a low level of E-cadherin (p = 0.02). Negative expression of Bcl-2 occurred in 75 % of cases. High level of p53 expression has been described as the main type of expression in these tumors, suggesting a combination of TB53 and BRCA1 mutations and a violation of cell death mechanism of in these tumors.

Conclusion. Breast cancer tumors of patients with hereditary mutations in BRCA1 gene demonstrate immunosuppressive type of microenvironment and a violation of the cell death mechanism. The main directions of future therapy of these tumors may include tumor immune microenvironment modification and activation of cell death mechanisms. 

40-52 469
Abstract

Background. Currently, there is growth evidence on prognostic and clinical differences in breast cancer (BC) associated with different types of BRCA1 / 2 mutations. At the same time, a triple negative tumor phenotype is not an absolute pathognomonic sign of BRCA1 / 2-associated cancer, where luminal phenotypes are being detected increasingly. In addition, attention is paid to the significance of estrogen signaling mechanism depending on the surrogate tumor type, including a triple negative phenotype due to alternative mechanisms.

Objective: to evaluate significance of BRCA1 / 2-mutations in luminal BC subtypes and multiple tumors.

Materials and methods. A prospective study conducted in Clinical Oncology Dispensary No. 1 in Krasnodar included 443 patients with breast cancer who underwent a genetic analysis on BRCA1 / 2 genes status by real-time polymerase chain reaction. In diagnostic cases of luminal phenotype and multiple cancers histological material and blood were sent to the N.N. Petrov Research Institute of Oncology of Ministry of Health of Russia to assess the mutation status of the BRCA1 / 2, ATM, CHEK2, NBS1, PALB2 genes by next-generation sequencing (NGS). Statistical analysis of clinical and morphological parameters correlated with mutational status was performed using the IBM SPSS Statistics v.22 statistical package.

Results. An interim analysis of data in April 2022 showed that 71 out of 304 breast cancer patients tested by polymerase chain reaction were found to be carriers of BRCA1 gene mutations. NGS method revealed 20 additional mutations of the BRCA1 / 2 genes: 11 BRCA1 mutations and 9 BRCA2 mutations. PALB2 mutation was also detected in 1 patient, NBS1 mutation – in 3, CHEK2 mutation – in 2, ATM mutation – in 2 patients. Out of 91 BRCA1 / 2-associated breast cancer 21 BRCA1-mutated tumors and 9 tumors with BRCA2-mutation demonstrated luminal phenotypes. The median age of breast cancer disease did not differ in BRCA1- and BRCA2-carriers (42 years versus 40 years, p ˃0.05). BRCA1 mutations are associated with poor differentiation (G3), BRCA2 mutations are associated with G2 (p ˂0.001). The BRCA2 mutation is characterized by a luminal tumor phenotype (p ˂0.001). There was no association of BRCA1 / BRCA2 gene mutations with T and N status (p ˃0.05). Of the 91 cases of BRCA-deficient tumors, 30 (33 %) patients had primary multiple cancer: 27 (90 %) with germinal mutation BRCA1 and 3 (10 %) with germinal mutation BRCA2. Contralateral breast cancer in the presence of germinal mutation BRCA1 was detected in 14 patients. The frequency of primary multiple cancer and contralateral breast cancer detection did not depend on the type of BRCA1 / 2 mutations (p ˃0.05).

Conclusion. With the primary multiplicity of the tumor process and the luminal subtype of the tumor, the determination of mutations by polymerase chain reaction in real time is clearly insufficient. It is obvious that the NGS method can identify additional pathogenic mutations that predict the clinical course and indicate the possibility of personalizing therapy and the need to test relatives, including tumors with luminal phenotype and tumors of several localizations. 

53-59 1222
Abstract

Background. The neutrophil to lymphocyte ratio (NLR) is a prognostic marker in various carcinomas, including breast cancer. The NLR reflects the balance of systemic immunity and is associated with survival in patients with solid tumors.

Aim. This study retrospectively evaluated the significance of the NLR and the absolute lymphocyte count in patients with breast cancer who received eribulin therapy.

Materials and methods. The prognostic significance of the NLR and the absolute lymphocyte count in 33 patients with metastatic breast cancer treated with eribulin in 2020–2021 was analyzed.

Results. The median follow-up time for patients was 9 [6; 15] months. Twenty-six of 33 (78.8 %) patients progressed. Seven of 33 (21.2 %) patients were censored due to therapy discontinuation, complete discontinuation after 1 course was required in 3 (9.1 %) patients and was associated with the development of hematological toxicity: 1 (3 %) case of a combination of grade 3 leucopenia and grade 3 thrombocytopenia, 2 (6 %) cases of grade 3 neutropenia. According to the analysis results, the NLR was a statistically significant risk factor for progression in patients on eribulin therapy, both without taking into account the influence of other factors (univariate model) and with the underlying influence of the absolute neutrophil count and the absolute lymphocyte count: hazard ratio (95 % confidence interval) was 1.21 [1.04; 1.41], p = 0.015 and 1.30 [1.07; 1.57], p = 0.008, respectively. There was no statistically significant effect of the absolute neutrophil count and the absolute lymphocyte count in both univariate and multivariate models. To illustrate the impact of SNL on the onset of progression, patients were divided into two subgroups based on median SNL: SNL˂ 2.46 and SNL ≥2.46. The median survival in patients with SNL ≥2.46 was 9 months, and in patients with SNL˂ 2.46 it was 15 months.

Conclusion. The results of the pilot study state the NLR is a potential prognostic marker of long-term treatment with eribulin for patients with metastatic breast cancer, and can be used in clinical practice. 

MAMMOLOGY. REVIEWS

60-66 325
Abstract

The aim of the work was to review randomized controlled trials regarding the efficacy of screening mammography in women aged 40–49 years.

Google Scholar and PubMed databases were searched for English-language publications for randomized controlled trials. Inclusion criteria were studies evaluating the possible benefit/harm of mammographic screening in women 40–49 years old, a follow-up period of at least 10 years, primary breast cancer, regarding as primary outcomes reduction of breast cancer mortality, and side effects screening mammography.

A search for the specified keywords found 2453 sources in electronic databases, of which only 83 studies were published as articles. After analyzing these studies, only 5 studies met the inclusion criteria. An analysis of these studies according to the inclusion criteria is subsequently presented in the article.

Based on the available data from randomized trials, no definitive conclusion about the effectiveness of mammographic screening in women 40–49 years of age can yet be drawn. Therefore, it is too early to draw a line in the debate about the appropriateness of mammography in the 40–49 age group.

GYNECOLOGY. ORIGINAL REPORTS

67-71 240
Abstract

The purpose of this study is to evaluate the possibilities of using the technique of determining the shear wave velocity in the differential diagnosis of pathologically altered lymph nodes in assessing the therapeutic effect of cervical cancer and endometrial cancer. The results of 20 patients with hyperplastic lymph nodes were analyzed, of which 8 patients were diagnosed with a cytologically confirmed metastatic lesion based on a set of ultrasound signs. When using the shear wave velocity estimation technique in these nodes, a high velocity was determined in all observations, the average value of which was about 2.9 m/sec, while in hyperplastic nodes of a benign nature, this velocity averaged about 1.3 m/sec.

72-76 268
Abstract

Cervical cancer is the second most common malignancy among Indian women. Every year, 122844 women are diagnosed with cervical cancer, with 67477 dying as a result of it. It primarily affects women between the ages of 15 and 44 who are in the reproductive age group1. This is primarily due to a delay in early cervical pathology diagnosis and treatment. From September 2017 to February 2018, a descriptive cross-sectional study was undertaken in the Obstetrics and Gynecology OPD at Govt. Erode Medical College, Perundurai, Erode District, Tamilnadu women ≥20 years age visiting Obstetrics and Gynecology OPD. The majority of women, 84.4 percent, married after they turned 18 years old (211). And 15.6 percent of the population was under the age of 18. Hinduism was followed by 97.2 percent, Christians by 1.6 percent, and Muslims by 1.2 percent. Doctors were the source of information for 36.3 % of those in our survey, while health workers educated 26 %. 25.9 % got their knowledge from the media, while 14 % got it from relatives and friends. According to our research, the most common reasons for refusing a Pap smear are dread of having to undergo a test (46.7 %) and a delay in receiving the results. When people are asymptomatic and have already been screened, 23 % believe it is unnecessary to go through the process again. They were not ready to acknowledge the requirement for pre-programmed serial screening.

The importance of immunization and the role of the vaccine for the human papillomavirus must also be educated. Given the main reason given by the participants for not having the test, it is critical that all health providers use every opportunity they have with women to educate and encourage them to do so. 

77-85 328
Abstract

Cervical cancer occupies a leading position in the structure of oncogynecological pathology. Radical trachelectomy (RT) has entered the standards of treatment of invasive cervical cancer in patients of reproductive age. RT can be performed by transabdominal and laparoscopic approaches. The purpose of our study was a comparative assessment of the effectiveness and study of the quality of life in patients after RT. In total, 99 surgical interventions were performed using technologies developed at Oncology Research Institute, Tomsk National Research Medical Center of Russian Academy of Sciences. The features and results of treatment are described, including oncological efficacy, reproductive results (reproductive potential, peculiarities of the course of pregnancies and childbirth). The analysis of the study of the quality of life of patients after RT according to the criteria of modern questionnaires EORTC QlQC30 and QLQ-CX24. 

86-92 325
Abstract

Transarterial chemoembolization (TACE) with drug-saturated microspheres is used in the treatment of women with pelvic tumors complicated by bleeding. Another serious problem is peritoneal carcinomatosis. However, it has not been studied whether TACE affects peritoneal lesions, is there a difference in peritoneal lesions with primary and recurrent tumors? The purpose of this article is to analyze the results of TACE in women with peritoneal lesions with primary and recurrent pelvis tumors. This is an analysis of 80 patients with primary tumors (group 1) and 20 patients with recurrent tumors of pelvis (group 2). 8 women in group 1 and 11 women in group 2 had an implantation lesion of peritoneum near the main focus, 3 women in group 1 and 4 women in group 2 had a peritoneum lesion at a distance from the main focus. Angiography revealed differences in blood supply of implantation metastases in the group of primary and recurrent tumors, as well as the blood supply of distant peritoneal metastases. These facts should be taken into account in order to reduce the number of errors in assessing the effectiveness of therapy, to obtain a good clinical result, and to avoid discrediting TACE due to unreasonable requirements for it. 

93-101 361
Abstract

Background. Cervical cancer (CC) still occupies a leading position in the structure of oncological diseases in the world. In the Republic of Tajikistan, there is a tendency for the growth of oncological diseases, and CC is consistently ranked second.

Objective: comparison of overall incidence rates of CC in the Republic of Tajikistan for the period from 2000 to 2020.

Materials and methods. To track the dynamics of CC in the structure of cancer incidence, we studied the data of reports on diseases of malignant neoplasms according to forms No. 7 and No. 35 of the Agency on Statistics under the President of the Republic of Tajikistan for the period 2000–2020.

Results. The incidence rates of cervical cancer in the republic ranged from 4.7–8.7 per 100,000 of the female population. A similar incidence of cervical cancer is noted in the most densely populated regions – Khatlon (3.5–9.9 per 100,000 female population) and Sughd (5.9–10.8 per 100,000 female population), lower rates in districts of republican subordination (3.3–7.9 per 100,000 women), and in the Gorno-Badakhshan Autonomous Region, the rates varied from 4.6 to 14.7 per 100,000 women, being the highest. CC most often occurred at the age of 35–64 years. CC can be detected at stages I–II in 65–83 % of cases. In 10–19 %, this is a locally advanced process that characterizes the III stage of the disease, and on average, every tenth patient with CC treats with an advanced process (stage IV). Every year, 50–93 % of patients die from the number of newly diagnosed cases. The highest rates of newly diagnosed cases of malignant neoplasms were noted in the B. Gafurov district – from 154 to 198 patients. In Panjakent and Kushoniyon district, these figures are 7–10 times lower: 27–74 and 23–44 cases, respectively. CC was the leading nosology in the structure of oncological morbidity in the Kushoniyon district, while in the district of B. Gafurov and the city of Penjikent, breast cancer was the leader for all the years under study.

Conclusion. Regional features can have a direct impact on the system of practical health care and their ability to provide quality care to the population, i. e. the remoteness and inaccessibility of the regions of residence determine the possibility of providing full-fledged medical care to the population, and, as a result, higher mortality rates from malignant neoplasms, in particular, CC. Consequently, our republic needs new approaches and views to reduce the mortality of women from CC in conditions of limited resources. 

102-108 269
Abstract

Secondary prevention of cervical cancer in the conditions of opportunistic cervical screening by co-testing in 5618 women over 30 years of age allowed to identify a high-risk group of cervical cancer for further examination using viral load assessment, immunocytochemical determination of the level of cancer proteins p16INK4a and Ki-67, extended video colposcopy and cervical biopsy with histological examination of surgical material. The obtained data demonstrated the expediency of changing the testing strategy by integrating the methods tested in the framework of opportunistic screening into the nationwide population screening program for cervical cancer. 

109-118 537
Abstract

This study was undertaken to analyze the effectiveness of cytological diagnostics of endocervical adenocarcinomas. We compared conventional liquid-based cytology, histology, immunohistochemistry, and molecular testing. A total of 25 endocervical adenocarcinomas, including endocervical adenocarcinomas in situ, were diagnosed using cytological methods over a year. Liquid-based cytology ensured better detection of glandular differentiation signs than conventional cytology. After molecular testing for human papillomavirus (HPV), we performed retrospective analysis of cytological characteristics of all endocervical adenocarcinomas (n = 15).

We identified specific cellular characteristics of HPV-associated typical and mucinous adenocarcinomas. We also observed 1 case of non-HPV-related clear-cell and 1 case of non-HPV-related mesonephral adenocarcinoma.

Our findings suggest that endocervical adenocarcinomas are a heterogeneous group of tumors. Endocervical adenocarcinomas accounted for 10.7 % of all primary cervical carcinomas (n = 214). Eighty percent of all endocervical adenocarcinomas were HPV-related, whereas the remaining 20 % were HPV-negative. We found no cytological differences between invasive endocervical adenocarcinomas and adenocarcinomas in situ.

Mutations detected in some of the patients are an important diagnostic criterion that specifies whether the tumor is rare. 

GYNECOLOGY. REVIEWS

119-126 415
Abstract

Historical standard of the first line endometrial cancer therapy was combination of paclitaxel and carboplatin. In more than a half of patients with advanced endometrial cancer receiving this combination, disease progression is observed after 2 years. Use of paclitaxel + carboplatin combination in adjuvant therapy requires search for effective regimens for progression after this systemic therapy. Chemotherapy effectiveness in progression after systemic therapy is low with a small exception: repeat administration of paclitaxel + carboplatin can be used after long platinum-free period. In a quarter of all patients with progression after systemic treatment, use of pembrolizumab monotherapy in case of microsatellite instability (or abnormalities in DNA reparation system) showed significant clinical benefit. Additionally, most tumors do not have abnormal DNA reparation system, and multitarget tyrosine kinase inhibitor and checkpoint inhibitor combination is considered pathogenetically justified. The first and only such regimen described in Russian clinical guidelines is lenvatinib and pembrolizumab combination which showed clinical benefit in the form of increased overall survival. 



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ISSN 1994-4098 (Print)
ISSN 1999-8627 (Online)