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Tumors of female reproductive system

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Vol 18, No 3 (2022)
View or download the full issue PDF (Russian)
https://doi.org/10.17650/1994-4098-2022-18-3

MAMMOLOGY. ORIGINAL REPORTS

14-23 504
Abstract

Background. The accurate and early diagnosis of breast cancer can improve efficacy of the treatment. The standard diagnostic methods such as mammography, ultrasound, and magnetic resonance tomography have a pivotal role in the detection of breast tumors, however, in some cases, they have low diagnostic accuracy. Mammoscintigraphy (MSG) / molecular breast imaging (MBI) with tumor-specific radiopharmacy 99mTc-Technetril in patients with breast cancer can considerably increase the accuracy of diagnosis. However, the diagnostic performance of MSG / MBI in the detection of different biological subtypes of breast cancer is still under investigation.

Aim. To evaluate the accuracy of MSG / MBI with 99mTc-Technetril in diagnosis of different biological subtypes of breast cancer.

Materials and methods. The analysis included the results of MSG / MBI of 1080 patients (2154 mammary glands), who were examined for suspected breast cancer. MSG / MBI were performed 5–15 min after intravenous injection into the vein of one of the feet of 370–740 MBq of tumor-specific radiopharmacy 99mTc-Technetril. Examinations performed from 2007–2020 was carried out on the emission computed tomography Forte (Philips); since 2020 the molecular visualization has been providing on the special gamma-camera Discovery NM750b (General Electric). The obtained data were evaluated by 2 experienced radiologists. Verification of changes in breasts was provided by morphological examination (1060 cases) or dynamic observation.

Results. The sensitivity, specificity and overall accuracy of MSG / MBI were 90 %, 98 %, 95 % correspondingly. When diagnosing tumors with a diameter of up to 10 mm, the sensitivity of MSG / MBI was decreased to 83 %. In patients with various biological subtypes, the sensitivity of MSG / MBI was as follows: luminal A – 88 %; luminal B– – 91 %; luminal B+ – 92 %; triple negative – 93 %; HER2-positive – 96 %. The intensity of tumor uptake depended on the biological subtype of breast cancer. The average values of the 99mTc-Technetril uptake coefficient were as follows: luminal A – 1.59; luminal B– – 1.71; luminal B+ – 1.95; triple negative – 1.93; HER2-positive – 2.22.

Conclusion. Retrospective analysis indicate high diagnostic performance of MSG / MBI: sensitivity – 90 %, specificity – 98 %, accuracy – 95 %. There are significant differences in the intensity of 99mTc-Technetril accumulation in tumors in patients with different biological subtypes of breast cancer (p = 0.01–0.004). MSG / MBI characterized by significant differences in the sensitivity in the diagnosis of luminal A and HER2+ breast cancer subtypes: 88 % and 96 %, respectively (p = 0.02).

24-28 356
Abstract

Postoperative radiation therapy after breast-conserving surgery is a standard method of treating breast cancer, but recently the issue of its de-escalation in patients older than 65 due to concomitant pathology, lower life expectancy and possible development of post-radiation complications has been discussed. The results of some foreign studies prove the absence of a statistically significant difference in relapse-free and overall survival in patients with early breast cancer older than 65 years with relatively favorable clinical and morphological characteristics without postoperative radiation therapy. We analyzed the long-term oncological results in patients with breast cancer older than 65 years after breast-conserving surgery without postoperative radiation therapy. The results of the study showed that postoperative radiation therapy in patients over 65 years of age with stage IA pT1N0M0 breast cancer of luminal immunophenotype A does not improve long-term oncological indicators. Thus, the exclusion of postoperative radiation therapy from the treatment plan of this group of patients is oncologically safe and economically justified.

29-39 416
Abstract

Background. Achieving a pathologic complete response (pCR) after neoadjuvant systemic therapy (NST) is a predictive factor for improving disease free and overall survival. In triple negative (TN) and HER2-positive breast cancer (BC), the pCR rate exceeds 60 %. Patients with TN and HER2-positive BC who demonstrate an excellent response to NST are like­ly ideal candidates for downsizing surgery. The condition for reducing the volume of surgical intervention is a reliable determination of pathologic complete response using instrumental imaging and biopsy methods.

Aim. To further assess the accuracy of post-NST image-guided biopsy to predict pCR.

Materials and methods. Sixty one patients with T1-3N0-3 triple negative or HER2-positive BC receiving NST in the Department of Breast Tumors of the NMRC of Oncology named after N.N. Petrov in the period from 2017 to 2019 were enrolled in this single-center retrospective trial. Patients underwent ultrasound-guided core-biopsy of the initial breast tumor region before surgery. Findings were compared with findings on pathologic evaluation of surgical specimens to determine the performance of biopsy in predicting pCR after NST.

Results. After neoadjuvant systemic therapy, clinical partial response (cPR) was diagnosed in 47 (77 %) patients, clinical complete response (cCR) in 14 (23 %) patients. pCR in the core-biopsy tissue and surgical material was achieved in 46 (75.4 %) and 37 (60.7 %), respectively. Performance of image-guided core-biopsy: sensitivity 100 % (95 % confldence interval (CI) 90.51-100), specificity 62.5 % (95 % CI 40.59-81.20), false-negative rate (FNR) 0 %, positive-pre­dictive value (PPV) 75.00 % (95 % CI 59.46-85.99), negative predictive value (NPV) 100.00 %.

Conclusion. This retrospective trial showed that ultrasound-guided core biopsies are accurate enough to identify breast pCR in patients with triple-negative or HER2-positive BC with good response after NST (FNR 0 %). Based on these results, a prospective clinical trial has commenced in which breast surgery is omitted in patients with a breast pCR after NST according to image-guided biopsy.

MAMMOLOGY. REVIEWS

40-51 483
Abstract

The paper presents an analysis of the latest literature data on the problem of obesity and breast cancer (BC). This review presents modern approaches to the diagnosis of BC in obese patients, new molecular methods of breast imaging,  analyzes the features of the course of BC with obesity depending on menstrual status, molecular biological subtypes of the tumor, the mechanisms of the development of BC against the background of obesity.

52-63 305
Abstract

Breast cancer (BC) has a leading position in the statistics of oncological morbidity and mortality among women. Taxan-based polychemotherapy regimens are an essential component of the complex therapy of the BC. However, currently used algorithms of taxan-based regimens application do not always provide with desire effect. It indicates the need to identify new prognostic markers and to develop new approaches to modify response of BC cells to standard therapeutic regimens. MicroRNAs, small RNA molecules regulating protein synthesis, are considered as promising markers and potential modulators of the BC cells sensitivity to taxanes.

The review includes a brief summary of the molecular mechanisms of action of the taxanes and the mechanism BC resistance to the process of microtubules depolymerization, provides with analysis of recent experimental and observational studies of the role of microRNAs in control of these mechanisms, and evaluates prospects for the development of new approaches to predict and to improve the cytostatic effects of taxanes through the analysis and modification of cellular microRNAs.

64-70 353
Abstract

Immediately after silicone implants were described, the technique of prepectoral implant placement dominated in breast reconstructive surgery. However, this plane soon had to be abandoned due to the high frequency of complications, such as infection, capsular contracture, explantation. For these reasons, surgeons soon had to switch to the subpectoral plane. Several decades later, thanks to the discovery of synthetic and biological meshes, surgeons returned to the prepectoral plane, but at a technically new level.

The purpose of this review was to analyze the role of biological and synthetic matrices as factors influencing the choice of the implant plane in one-stage breast reconstruction.

MAMMOLOGY. CLINICAL CASE

71-77 396
Abstract

Alveolar rhabdomyosarcoma is one of the four subtypes of rhabdomyosarcoma identified by the World Health Organization. This type of malignant neoplasms more often affects deep soft tissues of extremities and occurs in young ages, regardless of gender. According to the medical literature, no more than 45 cases of the development of primary cutaneous rhabdomyosarcoma have been reported in the world. In this report, we describe a clinical case of a 40-year-old woman with primary localization of alveolar radbomyosarcoma in the skin of the mammary gland.

78-88 344
Abstract

Current clinical recommendations indicate the need for a biopsy of a metastatic focus in metastatic breast cancer (BC), but the optimal frequency of additional molecular analysis remains unclear. The discordance of hormonal receptors (HR) between the primary tumor and metastatic foci has prognostic significance, while the transition from HR-positive BC to a triple negative phenotype is associated with a worse clinical prognosis. Acquisition of HR expression in primary triple negative BC is more favorable due to the wide range of options for HR-positive BC treatment. Over the past few years, PARP inhibitors have become an important therapeutic option for the treatment of various tumor types, including BC and luminal surrogate subtypes. However, some questions still remain unresolved, the most important of which are: what is the optimal sequence of the use of CDK4 / 6 inhibitors as part of combined hormone therapy and PARP inhibitors in luminal types of BRCA-associated BC and how effective is the strategy of PARP inhibition after the use of combined hormone therapy with CDK4 / 6 inhibitors? It is obvious that the answers to the questions can be partially obtained by performing a biopsy of the most clinically significant metastatic focus and selecting therapy according to the phenotypic surrogate subtype. A clinical case of the phenotypic evolution of HR-positive BRCA1-associated BC into a triple negative phenotype during metastasis to the lungs and the luminal phenotype of tumor metastasis in soft tissues is presented. Biopsy of the most clinically significant metastatic lesion in the lungs in this case changed the strategy of early-line therapy for estrogen-receptor-positive disease, when in the absence of a biopsy, a combined hormone therapy regimen with CDK4 / 6 inhibitors could be applied. At the same time, the strategy of using PARP inhibitor talazoparib, which has shown efficacy in all surrogate subtypes, should certainly be prescribed in the early line of therapy for BRCA-associated disease with loss of estrogen receptor expression. Despite the luminal phenotype of metastasis in the soft tissues of the back and the unknown status of bone metastases, the drug demonstrates efficacy in these cases as well. It should be noted that partial response according on RECIST 1.1 months with an improvement in the quality of life and the disappearance of pain syndrome was evaluated after 10 weeks of treatment. The response duration was an unprecedented 10 months.

GYNECOLOGY. ORIGINAL REPORTS

89-99 365
Abstract

Background. Endometrial hyperplasia is one of the most common pathologies of the female reproductive system. There is a high risk of transformation of an atypical form of endometrial hyperplasia into endometrial cancer, which takes a leading position in oncogynecological morbidity. Immunohistochemical markers can become predictors of endometrial malignancy, their role is currently being actively studied.

Aim. Search for molecular predictors of malignant transformation of endometrial hyperplasia.

Materials and methods. Histological and immunohistochemical studies were performed in 107 patients with diagnoses of endometrial hyperplasia without atypia (EH), endometrial atypical hyperplasia (EIN), endometrioid adenocarcinoma (EC). The tumor receptor status, MSI, expression of ARID1A, PTEN, β-catenin, PAX2, proliferation index (Ki-67) were determined by the immunohistochemical method according to the standard protocol.

Results. Loss of PAX2 expression was most common in precancerous and malignant endometrial cells. Loss of PAX2 expression was found in 89 % of cases in the EIN samples, in 86 % of cases in the EC samples and only in 2 cases of EH. Loss of PTEN expression was less common: with an equal proportion in 67 % of the samples of EIN and EC, while practically not occurring in women with benign GE. MSI was detected in 36 % of endometrial cancer samples. There was a deficiency in the DNA repair system in 1 case of EIN. Loss of ARID1A expression was detected in endometrial cancer with a frequency of 33 %. This gene functioned normally in all cases of EIN and EH. The expression of β-catenin was more pronounced in EC than in cases of EH. The Ki-67 proliferation index was statistically higher in the EC group than in EH and EIN.

Conclusion. Evaluation of morphological data and expression of the panel of markers PAX2, PTEN, ARID1A, β-catenin, Ki-67 index, PMS2 and MLH1 will improve diagnostic search in case of suspected malignancy of endometrial hyperplasia.

100-106 581
Abstract

Background. Persistently high incidence of cervical cancer in Russia and significant number of cases detected in the late stages necessitate the improvement of secondary prophylaxis of this disorder.

Aim. To assess risk factors for recurrent high-grade cervical intraepithelial neoplasia (CIN2+) (high grade squamous intraepithelial lesions, HSIL) after cervical conization.

Materials and methods. This study included 62 patients with recurrent HSIL treated in Novosibirsk Regional Clinical Oncology Dispensary, E. N. Meshalkin National Medical Research Center, “Zdorovye” LLC, “Avismed” LLC, Tomsk National Research Medical Center of the Russian Academy of Sciences, and Federal Research and Clinical Center for Specialized Medical Care and Medical Technologies, Federal Biomedical Agency of the Russian Federation in 2017–2021. We analyzed patients’ human papillomavirus (HPV) status, performed repeated examination of excised tissue specimens to evaluate the severity of lesions and resection margins, as well as immunohistochemical examinations. We found that mean time to cytologically confirmed recurrent HSIL was 16.0 ± 5.6 months. All patients were HPV-positive. Repeated histological examination demonstrated that 18 samples had positive resection margins or endocervical crypt involv ement. Fifty-seven samples had positive staining for p16 at immunohistochemical examination; 46 samples had  Ki-67 >30 %, which indicated high risk of recurrence. Treatment of patients with recurrent HSIL included repeated excision up to healthy cervical tissues, followed by intravaginal therapy with Cervicon-DIM 100 mg twice a day (for 3 months). Follow-up examinations after 18.0 ± 6.2 months on average showed no HPV persistence and no HSIL recurrence.

Conclusion. Endocervical crypt involvement along the primary resection margin, underestimated severity and depth of lesions (at the first surgery), and persistence of HPV infection are the main risk factors for recurrent cervical dysplasia or carcinoma in situ. Combination treatment that includes additional excision with a subsequent course of Cervicon-DIM is sufficient and effective.

GYNECOLOGY. REVIEWS

107-111 946
Abstract

The article presents updated data concerning the molecular mechanisms of influence of the well-known in clinical practice drug Mastodynon. The paper provides evidence of a significant effect of the compounds containing in its composition on the cell lines of a number of malignant neoplasms: breast cancer, hepatocellular carcinoma, leukemia and others. The data obtained are extremely attractive in the perspective of using the drug as a preventive agent.

GYNECOLOGY. CLINICAL CASE

112-117 401
Abstract

Trophoblastic neoplasias are rare tumors, accounting for less than 1 % of malignant neoplasms of the female genital tract. Trophoblastic tumors associated with developing pregnancy are extremely rare. The article presents the successful experience of diagnostics and treatment of intraplacental chorioncarcinoma associated with progressing pregnancy.



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