Breast cancer (BC) is the leading cause of morbidity and mortality of malignant neoplasms in women worldwide. In spite of a large number of studies devoted to the etiopathogenesis  of this group of malignant tumors, many questions concerning specific mechanisms of their origin and development are still unresearched. Based on numerous studies in recent years, in addition to traditional risk factors (such as hereditary factors, hormonal disorders, environmental factors, etc.), foreign and Russian authors have identified a new risk factor for BC development - the sphere of molecular disorders affecting circadian rhythms and circadian genes, as well as metabolic and regulatory intracellular pathways regulated by them. It has been shown that the balance between oncogenes and suppressor genes and processes such as neoangiogenesis, metastasis and antitumor immune response depend on the functioning of the circadian rhythm system. One of the key metabolites in the circadian rhythm regulation system is melatonin, which physiological effects extend not only to the central nervous system, but also to peripheral tissue cells. The study of the relationship between circadian rhythm disturbances, melatonin secretion and malignant tumors is one of the important tasks of modern oncology. In the present review the following aspects of this problem are considered in detail: relationships between circadian rhythms, melatonin and BC; molecular mechanisms of melatonin antitumor action in BC; therapeutic potential of melatonin in prevention and treatment of malignant breast tumors as a direct antitumor agent, a component of accompanying treatment, and as a radiosensitizer and radioprotector for radiotherapy. The purpose of this review is to investigate the problem of the relationship between the circadian rhythm system, melatonin and molecular mechanisms of development and progression of breast malignancies, as well as the therapeutic potential of melatonin in their prevention and treatment. The review is based on the study of relevant and reliable scientific articles, reviews, meta-analyses, systematic reviews, and clinical trials published in Scopus, PubMed, Web of Science and in peer-reviewed Russian journals mainly during the last 5 years.

This article reviews literature on organ-sparing and oncoplastic surgeries for breast cancer. Initially, we performed organ-sparing surgeries in patients with stage I—IIA breast cancer and then compared outcomes with those in patients after radical mastectomy. Since there were no differences in both overall and relapse-free survival between the groups, we started to perform organ-sparing surgeries in women with locally advanced breast cancer after neoadjuvant therapy who achieved complete or partial response. Oncoplastic resections were used to achieve good aesthetic results and also for patients in whom classical organ-sparing resection would inevitably result in a poor cosmetic outcome due to the tumor location. In recent years, the technique of extreme oncoplastic breast resection has emerged as a promising option that extended the scope of indications to organ-sparing treatment. In particular, it allows breast conservation for patients with multicentric, multifocal tumors, and tumors >50 mm. All organ-sparing and oncoplastic operations first of all improve the quality of life of breast cancer patients. 

Breast cancer is the main cause of cancer death in women under the age of 40. However, the organized mammographic screening of a young healthy woman was recognized by most experts as ineffective. This article is a brief overview about understanding of the risks of developing breast cancer in young women and a possible personalized screening in this group of patients.

The list of indications to adjuvant radiation therapy for breast cancer patients was extended in recent years, regardless of the type of reconstruction. Surgeons and radiologists have to choose the most appropriate sequence of reconstruction and to reduce the risk of complications. Radiotherapy is one of the main factors causing complications in patients undergoing breast reconstruction, and vice versa, the implant might hinder radiotherapy, preventing proper delivery of the required radiation dose. Both oncologists and radiologists try to reduce the incidence of complications, which is an important interdisciplinary aim. This article investigates international experience of well-known cancer centers and experience of the Department of Oncology and Reconstructive Breast and Skin Surgery, P.A. Herzen Moscow Oncology Research Institute, a branch of the National Medical Radiology Research Center, Ministry of Health of Russia. We analyzed the choice of the breast reconstruction method in patients undergoing radiotherapy after surgery and developed recommendations for choosing an optimal method of reconstructive surgery.

Background. Surgery is fundamental in complex and combined approach in the treatment of the early breast cancer. It is a common fact, that absence of tumor cells in the resection margin is the main indicator of oncological safety of the breast-conserving surgery (BCS). The presence of tumor cells in examined margin is the predictor of local recurrence after BCS for breast cancer. Currently the clinical need for precise and fast method of intraoperative assessment of the resection margin status is kept. Intraoperative evaluation of the resection margin with the usage of digital two-point sectorography (Faxitron PathVision) appeared as the alternative to intraoperative histological examination, providing the optimum size of the information about adequacy of the carried out surgical treatment.

Aim. To evaluate diagnostic features of the digital two-point sectorography Faxitron PathVision in the intraoperative assessment of the resection margin status after the surgical treatment in comparison with planned histologic examination.

Materials and methods. 368 conducted conservative surgeries were analyzed; patients were divided in two groups depending on neoadjuvant chemotherapy. The first group of patients included 236 patients, who didn't receive neoadjuvant chemotherapy before surgery; second group included 132 patients, who received neoadjuvant chemotherapy. Subset analysis of detection rate of the positive resection margin (R1) was carried out with the usage of the intraoperative assessment of the resection margin on the X-ray device Faxitron PathVision or without this method. After each BCS resection margin status was assessed on planned histologic examination for the presence of the tumor cells, with subsequent analysis of the frequency of reoperations when R1 was found.

Results. In 368 tested surgical specimens after BCS R1 was found in 25 cases, which is 6.8 %. From 236 patients in the first group after BCS R1 was found in 20 cases, which is 8.5 %; from 132 conducted operations in the second group in 5 (3.8 %) cases the presence of R1 is found. Reoperations were performed in 13 cases and tumor cells were found in 3 cases in the sub-group which didn't receive intraoperative assessment with X-ray device Faxitron PathVision.

Conclusions. Assessing the results of our study we can make a conclusion about the positive experience of performing BCS and intraoperative evaluation of the resection margin with the usage of the digital two-point sectorography (Faxitron PathVision) and low frequency of R1 (3.8 %) in comparison with absence of this method (8.5 %).

Background. One-stage prepectoral implant-based reconstruction (OSPIBR) using biocompatible synthetic meshes support gained wide popularity in breast cancer surgery. Optimal structure of polypropylene mesh implants (PMI) and methods of its application are actively discussed.

Aim. To study the effectiveness and safety of prosthesis support with “heavy” PMI in OSPIBR. 

Materials and methods. During 2019-2021 18 OSPIBR with "heavy" PMI support were performed after subcutaneous mastectomies in 14 patients. Cancer was indication for surgery in 13 cases (two of them - with BRCA1 mutation) and BRCA1 mutation solely - in 1 case. Foamed polyurethane covered silicone prosthesis (Polytech, Germany) was used for OSPIBR and "heavy" PMI PROLENE™ Polypropylene Mesh (Ethicon/Johnson & Johnson, USA) for prosthesis support by original method.

Results. The overall complication rate was 5.6 % (1/18). It was a minor complication: limited aseptic skin necrosis along incision edge, successfully excised under local anesthesia. No cancer recurrences or capsular contracture formation were registrated during follow-up (6 months). The cosmetic outcome (Harvard score) was excellent in 11 of them and good in 3.

Conclusions. "Heavy" PMI application by original technique in OSPIBR after subcutaneous mastectomy for breast cancer is a safe and effective method of prosthesis support.

Background. In recent years, there has been an increase in the incidence of vulvar precancer (lichen sclerosus), as well as vulvar cancer. Since this disorder is rare, treatment planning and therapy itself are often suboptimal, which results in a high recurrence rate. Treatment of patients with local recurrence is even more difficult. Improper therapy often leads to fatal outcomes.

Aim. To develop an innovative therapeutic approach to local recurrent vulvar cancer that includes combination (intraarterial and systemic) chemotherapy and surgery.

Materials and methods. This pilot study included two patients with a second episode of local recurrent vulvar cancer. The first patient was denied special treatment, whereas the second one was offered abdominoperineal resection of the rectum. At the first stage, the patients received combination chemotherapy; at the second stage, they had combination reconstructive surgeries.

Results. Combination chemotherapy was highly effective as demonstrated by the reduction of the recurrent tumor to a resectable size. Combination and reconstructive surgeries allowed us to preform radical treatment and preserve functions of the adjacent organs.

Conclusion. Combination treatment was highly effective in patients with local recurrent vulvar cancer, when the tumor was located near the urethra, vagina, and anus or invaded them. Combination chemotherapy ensured good tumor regression, while surgery gave hopes for a favorable outcome.

Background. Breast cancer is the most common cancer among women. Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, in which there are no special targets for therapy. Therefore chemotherapy is still leading treatment for TNBC including the regiments with platinum drugs.

Aim. To study the association of polymorphic markers of the genes XRCC1 (rs25487), ERCC5 (rs17655), TP53 (rs1042522), CDKN1A1 (rs1801270) with progression-free survival (PFS) and overall survival (OS) of TNBC patients after platinum-based neoadjuvant chemotherapy.

Materials and methods. Polymorphic markers of the XRCC1, ERCC5, CDKN1A and TP53 genes were studied in blood samples of 67 patients with stage II–III TNBC by real-time polymerase chain reaction with fluorescent allele-specific probes. The results of determining the markers were compared with PFS and OS using the Kaplan–Meyer method and the log-rank-test.

Results. The association was found for the polymorphic marker rs25487 of the XRCC1 gene with PFS (carrying the T/T genotype was associated with a decrease of median PFS: 15.6 months versus 34.3 months, p = 0.013) and OS (carrying the T allele was associated with a decrease of median OS: 24.3 months versus 34.6 months, p = 0.041) without depending on the BRCA status. For the polymorphic marker rs17655 of the ERCC5 gene, significant difference in PFS was obtained in the period from 15.4 to 60.0 months of follow-up (the carrier of the C allele was associated with a decrease of median PFS: 20.0 months versus 35.2 months, p = 0.035). When considering the genotypes of the polymorphic marker of the ERCC5 gene differences were revealed between patients with the C/C genotype (M = 15.9 months) and two other genotypes (M = 33.6 months), p = 0.039. For the polymorphic marker rs1801270 of the CDKN1A gene significant differences in PFS were obtained in the period from 15.4 to 60.0 months of follow-up (for carriers of allele A, a decrease in median PFS was observed: 16.6 months versus 32.0 months, p = 0.046). For the polymorphic marker of the TP53 gene (rs1042522) a tendency to decrease OS for carriers of the C/C genotype was found seems promising for further study.

Conclusion. The association of the studied polymorphic markers of the genes XRCC1 (rs25487), ERCC5 (rs17655) and CDKN1A (rs1801270) with PFS was revealed in patients with TNBC. Association with OS was obtained for the polymorphic marker of the XRCC1 gene (rs25487). These data may allow for further validation to individualize the treatment of this category of patients.

A clinical case of primary multiple metachronous malignant breast tumors and a rare malignant schwannoma of the right hip is presented. Difficulties in differential diagnosis arose with the appearance of a metastatic process in the lungs, solving the issue of their source and further treatment. In oncological practice, only morphological examination can finally verify the diagnosis. The choice of treatment regimen depends on the affiliation of metastases to a particular tumor. At the first immunohistochemical examination, tumor foci in the lung were regarded as breast cancer metastases, which it allowed to conduct 4 courses of polychemotherapy according to the TS scheme (paclitaxel + cyclophosphane) with negative dynamics. This led to doubt about the correctness of determining the source of the metastatic process. Repeated immunohistochemical examination revealed that the metastatic lesion of the lung tissue was a consequence of the progression of malignant schwannoma of the right hip. Appropriate polychemotherapy was prescribed.

Background. Applied standard methods of cervical cancer (CC) treatment have several disadvantages in terms of local and systemic toxicity and the risks of local recurrence. Our study proposed the use of neoadjuvant chemotherapy (NACT) in a dose-dense mode, followed by radical hysterectomy, in order to improve the results of treatment of locally advanced CC (IB2-IIB stages) (FIGO)/T1b2-2bN0M0 (TNM).

Aim. Improvement of immediate and long-term results in treatment of locally advanced CC IB2-IIB stages (FIGO), determining the immediate effectiveness of dose-dense NACT, based on magnetic resonance imaging (MRI) data, and the identification of prognostic factors for tumor response to chemotherapy.

Materials and methods. Between April 2016 to November 2019 120 women with IB2-IIB stages (FIGO) were included in this study. Of these, 58 patients underwent 3 cycles of intensified NACT according to the AP scheme (cisplatin 75 mg/m², doxorubicin 35 mg/m²) and 62 patients underwent NACT according to the TR scheme (cisplatin 60 mg/m², paclitaxel 60 mg/m²). The assessment of the effect of intensified NACT was performed according to the RECIST 1.1 criteria according to MRI data. Also 2 retrospective groups of patients were recruited: group I - surgical treatment without preoperative chemotherapy (25 patients with IB2-IB3 stages (FIGO) from November 2009 to August 2019), group II - concurrent chemoradiotherapy (44 patients with stage IIB cervical cancer (FIGO) from January 2013 to June 2018).

Results. Complete clinical response was detected in 12 (10.0 %) patients, partial response - in 69 (57.5 %) patients, stable disease - in 35 (29.2 %) patients, progression was observed in 4 cases (3.3 %). After NACT in a dose dense mode, due to an objective clinical response (complete response, partial response and stable disease for stage IIA according to RECIST 1.1 criteria), 99 (82.5 %) patients underwent surgical treatment. For 21 (17.5 %) patients due to the absence achievement of objective clinical response (stable disease for stage IIB according to RECIST 1.1 criteria or progression), performed concurrent chemoradiotherapy. During the observation period, 113 (94.2 %) patients remained alive. Mortality for the first year was 1.7 % (2 cases). There was a coincidence of the results of a complete response according to MRI in 11 (91.7 %) cases out of 12 cases with the pathology data. According to multivariate analysis, it was revealed that parametrial invasion, according to the histological examination of the surgical material, is an independent prognostic factor for recurrence. According to comparative evaluation of disease-free survival curves between groups of IB2-IIB stages (FIGO) patients who received and did not receive dose-dense chemotherapy, it was found that disease- free survival in the group with NACT was higher compared to the group without NACT (p = 0.03, the log-rank criterion).

Conclusions. The use of dose-dense NACT is an effective treatment mode for patients with IB2-IIB CC (FIGO), which in most cases allows achieving a tumor response with subsequent improvement in immediate and long-term results and can be considered as an alternative to standard treatment for locally advanced CC.

Cervical cancer is a very preventable disease that poses a significant threat to women, especially in countries with low economic development. The aim of the study was to study some aspects of the psychological status of patients with cervical cancer. The psychological status of patients with cervical cancer (n = 83) was studied at the Osh Interregional Oncology Center (Republic of Kyrgyzstan) using the hospital scale of anxiety and depression (HADS) and the scale of self-assessment of the level of reactive and personal anxiety (the test of Spielberger-Khanin). Patients diagnosed with cervical cancer are a vulnerable group for the development of psychological disorders, and they need screening programs that can potentially identify candidates for psychotherapeutic treatment. The hospital scale of depression and anxiety showed that patients of both fertile and postmenopausal age have a high frequency of clinically expressed anxiety, more common among the latter. However, signs of depression were more pronounced among those of fertile age, compared with postmenopausal. Regarding reactive and personal anxiety, the frequency of their spread was the same among people of fertile and postmenopausal age.

Background. Evaluation of a tumor-associated marker SCCA (squamous cell carcinoma antigen) level is used in cervical squamous cell carcinoma (CC) to predict the course of the tumor process, monitor the effectiveness of chemo- and chemoradiotherapy, and for preclinical detection of recurrence in follow-up of patients after the completion of primary treatment. However, publications devoted to the study of the possibility of using SCCA level as an additional criterion for the effectiveness of neoadjuvant intra-arterial chemotherapy (IACT) are still rare.

Aim. Study of the tumor marker SCCA level in patients with locally advanced squamous CC during neoadjuvant IACT as an additional factor in assessing its effectiveness.

Materials and methods. 53 patients with locally advanced squamous CC IB—IVB stages (T1b-3bN0-1M0-1) were included to the study. The mean age of patients was 45.6 years (25-64 years). All patients underwent superselective neoadjuvant IACT with cisplatine (in combination with intravenous administration of docetaxel or paclitaxel). Serum SCCA levels in CC patients were assessed before the first and after the second course of neoadjuvant IACT compared to the clinical effect of treatment after two courses (RECIST 1.1 criteria).

Results. SCCA level after 2 courses decreased in all patients with initially increased its level, while the proportion of SCCA-positive cases decreased from 71.7 to 26.4 %. When baseline SCCA values were normal, a complete response was achieved more often than with initially elevated levels (26.7 % vs 15.8 %), while distribution by tumor stages was similar in both subgroups. It has been established that if, after 2 courses of neoadjuvant IACT, SCCA levels exceeds 2.1 ng/ml and/or (for patients with initially increased SCCA value) it decreased by less than 60 % from the baseline, probability to achieve complete response after realization of effect of 2 courses of IACT was extremely small. Strong correlation (R = 0.829) between initial level of SCCA and degree of its decrease after 2 courses of IACT was discovered in the group of patients with complete response after the second course of IACT. It was getting lower in partial response group (R = 0.778) and stabilization group (R = 0.750).

Conclusion. Dynamics of SCCA level after 2 courses of IACT in squamous CC patients can be used as additional criterion of the degree of treatment effectiveness.

Background. Difficulties in the prevention and treatment of endometrial pathology in hormone-positive breast cancer are associated with the lack of an unambiguous understanding of the mechanisms of the effect of tamoxifen on target tissues and the development of possible hyperestrogenism.

Aim. To study the effect of ovarian steroidogenesis on the endometrium during adjuvant therapy with tamoxifen in pre-menopausal patients with hormone-dependent breast cancer.

Materials and methods. All patients at inclusion in the study had intact menstrual function and received adjuvant therapy with tamoxifen. Group 1 included 42 patients without chemotherapy, group 2 included 41 patients with chemotherapy. Depending on the safety of the menstrual function, each group was divided into 2 subgroups. At the control points (3, 6 and 9 months from the start of tamoxifen therapy) patients underwent transvaginal ultrasound with measurement of endometrial thickness, and also determined the content of follicle-stimulating hormone and estradiol in peripheral blood. When menstruation persisted, blood sampling and measurement of endometrial thickness were performed on days 5-8 of the menstrual cycle.

Results. In subgroups 1A and 2C, patients with preserved menstrual function showed a trend towards higher values of estradiol levels and endometrial thickness, compared with subgroups 1B and 2D of patients with amenorrhea. Against this background, the absence of statistically significant intergroup differences in the content of follicle-stimulating hormone in patients receiving tamoxifen with a preserved menstrual cycle (1A and 2C) and amenorrhea (1B and 2D) attracts attention. An intragroup analysis of follicle-stimulating hormone dynamics in patients with amenorrhea without chemotherapy in subgroup 1C shows an increase in its content by 162 %, without statistically significant changes in endometrial thickness and estradiol concentration. The statistically significant increase in endometrial thickness by 25 % and the proportion of patients with increasing endometrial wall thickness in 63.3 % in the 2D subgroup in patients receiving tamoxifen, with amenorrhea and previous chemotherapy treatment are cause for concern.

Conclusion. The results of the study indicate a possible additive effect of such factors as intact menstrual function before the start of treatment for hormone-positive breast cancer, chemotherapy, and the development of amenorrhea on the progressive increase in endometrial thickness when using tamoxifen in premenopausal patients.

The prevalence of vaginal atrophy is particularly high among women who have undergone treatment for gynecological cancers, since they have significantly lower estrogen levels and altered vaginal microbiota. These patients often experience vaginal discomfort, dryness, and pain, but rarely report this to a doctor. Such symptoms affect patients’ quality of life and might cause a family breakdown. This article proposes a safe therapeutic option for women with vulvovaginal atrophy resulted from gynecological surgeries or comprehensive treatment for gynecological cancers. It provides a rationale for the local application of Estrogial™ containing hyaluronic acid. Elimination of symptoms, such as burning, itching, swelling, and hyperemia of the vulval vestibule and perineal tissues ensured maximum compliance to treatment in cancer patients and improved their quality of life after combination therapy.

Malignant transformation of endometrioid heterotopias develops in 0.7-2.5 % of cases; 75 % of cases have an ovarian localisation and 25 % an extraovarian one. As it has been suggested that malignant endometriosis-associated neoplasia (MEAN) is developed in foci of atypical endometriosis. The review describes the mechanisms of carcinogenesis, the clinical and morphological features of the disease, and the principles of therapy. MEAN usually occur in younger women, are detected at stages I-II, and are mostly represented by clear cell and endometrioid carcinomas, but rare histological types have also been described. CTNNB1, PTEN, PIK3CA and ARID1A mutations are often detected in MEAN. The treatment of MEAN is not standardised, there are no prospective randomized trials assessing treatment. Patients with ovarian MEAN receive therapy similar to epithelial ovarian cancer. Patients with extraovarian localisation represent a subgroup that of patients that may require a personalised approach.

Deficient DNA mismatch repair (dMMR) is a rare molecular disorder found in 20-30 % of endometrial tumors. Laboratory identification of dMMR/microsatellite instability (MSI) has a high diagnostic value, since these impairments are considered as biomarkers of endometrial adenocarcinoma. They help to identify patients at high risk of Lynch syndrome, evaluate the disease prognosis, and estimate the efficacy of immune checkpoint inhibitors and their combinations. This review details current concepts of MSI diagnostics and discusses its predictive value in patients with endometrial cancer. It also describes a new diagnostic algorithm for the detection of dMMR and MSI.