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  • 1
    Online Resource
    Online Resource
    Assessment of 〈i〉ERBB2〈/i〉 and HER2 expression in metastatic breast cancer using the nCounter® system and a 100‑gene scale
    Publishing House ABV Press ; 2023
    In:  Tumors of female reproductive system ( 2023-09-29)
    Details
    In: Tumors of female reproductive system, Publishing House ABV Press, ( 2023-09-29)
    Abstract: Background. Individual molecular characteristics of a tumor can serve as a basis for a tailored approach to therapy, prediction of the disease course and outcome, and timely treatment correction in cancer patients. Tumor genomic profiling allows for a more precise tumor assessment in an individual manner. Accurate identification of the HER2 status of a breast tumor is crucial for clinical decisions and appropriate treatment strategy. Aim. To increase the efficacy of systemic therapy for breast cancer, reduce inappropriate prescribing, and ensure a tailored approach to systemic breast cancer therapy using the information on individual molecular characteristics of the tumor. Materials and methods. We explored the expression of 100 genes involved in breast cancer development in 106 tumor samples from patients with metastatic breast cancer. We used the nCounter technology based on direct digital target detection using color‑coded molecular barcodes. We analyzed the expression of 28 genes with a high predictive value for breast cancer. Results. The nCounter technology allowed us to perform semiquantitative assessment of the expression of 28 genes in tumor tissue samples. We compared the expression of ERBB2 and HER2. The HER2 expression between 252.32 and 6000 barcodes was equivalent to HER2 (0) status; between 6000 and 9196.25 barcodes, to HER2 (1+); between 9196.25 and 15022.46, to HER2 (2+ / ISH±); and ≥15022.46 barcodes, to HER2 (3+). In case of HER2 (3+) and ERBB2 below 6000 barcodes, the result was considered false positive. In case of HER2 (0) or (1+) and ERBB2 above 15000 barcodes, the result was considered false negative. In 18 tumors, the discrepancies in the results meant two principally different breast cancer subtypes requiring different treatments; in 2 cases, the discrepancies were in the level of HER2 expression. Conclusion. HER2 testing should be performed on an excision sample (ideally on the same block that was used for genomic testing). Despite the correlation between the HER2‑enriched molecular class and the response to anti‑HER2 therapy, the final result on HER2 status in discordant cases should be based on currently approved assays after results validation.
    Type of Medium: Online Resource
    ISSN: 1999-8627 , 1994-4098
    URL: Article
    DOI: 10.17650/1994-4098-2023-19-3-00-00
    Language: Unknown
    Publisher: Publishing House ABV Press
    Publication Date: 2023
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  • 2
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    Online Resource
    The role of platinum-based antineoplastic drugs and their impact on complete pathological response and prognosis in patients with BRCA-associated triple-negative breast cancer after neoadjuvant treatment: a single institution experience
    Publishing House ABV Press ; 2023
    In:  Tumors of female reproductive system Vol. 19, No. 1 ( 2023-06-25), p. 48-55
    Details
    In: Tumors of female reproductive system, Publishing House ABV Press, Vol. 19, No. 1 ( 2023-06-25), p. 48-55
    Abstract:    Background.  BRCA-associated triple negative breast cancer (TNBC) is considered one of the most aggressive subtypes of breast cancer with high sensitivity to chemotherapy, which leads to increased interest in finding new treatment options for patients with this subtype of breast cancer.    Aim.  To determine the role of adding a platinum drug to standard systemic neoadjuvant therapy (NAC) for patients with primary BRCA-associated TNBC with clinical stage T1–3N0–3M0, and to evaluate the effect of platinum-based drugs on recurrence-free survival in patients of this category.    Materials and methods.  The study included 75 patients diagnosed with primary BRCA-associated TNBC. They were divided into 2 groups depending on the NAC provided, and then they were subdivided depending on the completion of the course of ongoing NAC, the final pathomorphological result and the presence of recurrence.    Results.  Group I included 48 (64 %) patients who received the AC–T regimen; in group II (n = 27 (36 %)) patients received NAC according to the AC–TCarb regimen. Patients of group II showed a higher frequency of achieving pathological complete response (pCR) compared with patients of group I (73.7 % versus 41.2 %, respectively, p = 0.0433). Taking into account the NAC regimens being carried out, patients of group I had a slightly higher risk of recurrence compared to patients of group II (p = 0.099).    Conclusion.  In patients with primary BRCA-associated TNBC, the addition of platinum compounds to the systemic NAC resulted in achieving of pCR in 73.7 % cases compared with 41.2 % pCR after the standard anthracycline-taxane NAC, which entails a reduced risk recurrence in this category of patients. Performing a full course of planned NAC has a positive trend in achieving pCR in patients of this category.
    Type of Medium: Online Resource
    ISSN: 1999-8627 , 1994-4098
    URL: Issue
    URL: Article
    DOI: 10.17650/1994-4098-2023-19-1
    DOI: 10.17650/1994-4098-2023-19-1-48-55
    Language: Unknown
    Publisher: Publishing House ABV Press
    Publication Date: 2023
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  • 3
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    Online Resource
    Accuracy of core biopsy image-guided post-neoadjuvant chemotherapy breast to predict pathologic complete response
    Publishing House ABV Press ; 2022
    In:  Tumors of female reproductive system Vol. 18, No. 3 ( 2022-12-01), p. 29-39
    Details
    In: Tumors of female reproductive system, Publishing House ABV Press, Vol. 18, No. 3 ( 2022-12-01), p. 29-39
    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.
    Type of Medium: Online Resource
    ISSN: 1999-8627 , 1994-4098
    URL: Issue
    URL: Article
    DOI: 10.17650/1994-4098-2022-18-3
    DOI: 10.17650/1994-4098-2022-18-3-29-39
    Language: Unknown
    Publisher: Publishing House ABV Press
    Publication Date: 2022
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  • 4
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    Online Resource
    Predictive multigenic scale. Analysis of own results in metastatic breast cancer
    Publishing House ABV Press ; 2023
    In:  Tumors of female reproductive system Vol. 19, No. 1 ( 2023-06-25), p. 69-81
    Details
    In: Tumors of female reproductive system, Publishing House ABV Press, Vol. 19, No. 1 ( 2023-06-25), p. 69-81
    Abstract:    Background.  Breast cancer is one of the most common female malignancies. Molecular diagnostic methods of tumor profiling allow us to analyze individual tumor characteristics, identify new prognostic and predictive markers.    Aim.  To increase the efficacy of systemic therapy for breast cancer and reduce inappropriate prescriptions using the data on individual molecular tumor characteristics; to develop a polygenic panel to ensure a tailored approach to systemic therapy for breast cancer.    Materials and methods.  We analyzed 84 tumor tissue samples from pre- and postmenopausal women with metastatic breast cancer who were treated and followed-up in 6 healthcare institutions. We assessed expression of genes involved in breast cancer. In a pilot study, we analyzed archived paraffin-embedded tumor specimens form 12 out of 1,216 patients with T1–2N0M0 breast cancer included into retrospective analysis. Gene expression was assessed using the nCounter technology based on direct digital detection of targets using fluorescent barcodes (nCounter Analysis System; NanoString Technologies, USA). Tumor tissue (biopsy and surgical specimens) was analyzed. The choice of genes was based on the literature data and experience in the development of other polygenic panels, as well as clinical significance of markers of prognostic scales. Gene mutations were confirmed by next generation sequencing and reverse transcription-polymerase chain reaction.    Results.  We analyzed the expression of 28 genes with a high predictive value that have been substantially studied (including ESR1, PGR, PIK3CA, BCAR4, BCAS2, CCND1, CCND2, CCND3, FOXA1, Erb2, EGFR, CDH3, FOXC1, KRT14, KRT5, CD274, CDK4, CDK6, P53, PTEN, BRCA1, BRCA2, CHEK2, CLDN3, CLDN7, AR, TOP2a, TUBBIII). We identified 29 cases of discrepancy (29 / 84; 34.5 %) in tumor subtype, including 11 cases of luminal A and B breast cancer, which might potentially affect the choice of the treatment regimen. In 18 cases, there were some principal discrepancies in the tumor subtype that implied totally different treatment regimens. The proposed polygenic signature allows accurate identification of the tumor subtype in patients with metastatic breast cancer and choice of an optimal treatment strategy.    Conclusion.  We have developed a 100-gene signature including molecular subtypes of breast cancer (luminal A, luminal B, basal, claudin-like) and treatment-oriented clusters. Molecular tumor profiling using this polygenic signature is an accurate method for determining tumor subtype in patients with breast cancer, which enables a tailored approach to therapy.
    Type of Medium: Online Resource
    ISSN: 1999-8627 , 1994-4098
    URL: Issue
    URL: Article
    DOI: 10.17650/1994-4098-2023-19-1
    DOI: 10.17650/1994-4098-2023-19-1-69-81
    Language: Unknown
    Publisher: Publishing House ABV Press
    Publication Date: 2023
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  • 5
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    Online Resource
    The role of neoadjuvant chemotherapy of triple-negative breast cancer in St. Petersburg City Clinical Oncological Dispensary
    Publishing House ABV Press ; 2016
    In:  Tumors of female reproductive system Vol. 12, No. 2 ( 2016-01-01), p. 26-34
    Details
    In: Tumors of female reproductive system, Publishing House ABV Press, Vol. 12, No. 2 ( 2016-01-01), p. 26-34
    Type of Medium: Online Resource
    ISSN: 1999-8627 , 1994-4098
    URL: Issue
    URL: Article
    DOI: 10.17650/1994-4098-2016-12-2
    DOI: 10.17650/1994-4098-2016-12-2-26-34
    Language: Unknown
    Publisher: Publishing House ABV Press
    Publication Date: 2016
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  • 6
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    Online Resource
    Prognostic and predictive value of a novel 100-point scale in patients with T1–2N0M0 breast cancer
    Publishing House ABV Press ; 2023
    In:  Tumors of female reproductive system Vol. 19, No. 1 ( 2023-06-25), p. 56-68
    Details
    In: Tumors of female reproductive system, Publishing House ABV Press, Vol. 19, No. 1 ( 2023-06-25), p. 56-68
    Abstract:    Aim.  To increase the efficacy of systemic breast cancer therapy and reduce inappropriate prescriptions using individual immunohistochemical tumor characteristics, as well as to develop prognostic scales to ensure a tailored approach to adjuvant systemic treatment in breast cancer patients.    Materials and methods.  We conducted a comprehensive study that included collection of literature data on clinical, pathomorphological, prognostic, and predictive factors of breast cancer, as well as a retrospective cohort study using the data from the cancer registry. We also performed histological and immunohistochemical examination of tumor tissue samples from breast cancer patients (for the retrospective cohort study) and statistical data analysis. A total of 1,216 patients with T1–2N0M0 breast cancer were included in this study. Histological and immunohistochemical examinations of tissue samples (paraffin blocks) were conducted in the laboratory of N. N. Petrov National Medical Research Center of Oncology. We stained slides for both routinely used markers (including estrogen receptors, progesterone receptors, HER2, and Ki-67) and other markers (CK14, FOXA1, FOXP3, PD-L1, P53, SMA, androgen receptors, E-cadherin, CD4, CD8, CK5 / 6, EGFR).We analyzed risk factors for lethal outcomes in patients from this group to develop prognostic scales and compared their results.    Results.  We evaluated the most clinically and statistically significant factors affecting mortality. Using logistic regression, we chose 10 factors that had the greatest impact on the outcomes and then produced several scales, includinga 10-point regression scale (based on 10 most significant factors identified). Survival analysis in high-risk and low-risk patients using the regression scale demonstrated significant differences between these groups (р 〈 0.00001). The assessment of adjuvant chemotherapy efficacy in the combined group of intermediate- and high-risk patients (as estimated by the regression model) showed that intermediate- and high-risk patients receiving adjuvant chemotherapy had significant differences in their survival (р = 0.0057). The regression scale for 10-year prognosis demonstrated sufficient sensitivity (58.05 %), specificity (69.47 %) and ef fectiveness (63.76 %).    Conclusion.  Our regression prognostic scale includes markers with a high prognostic value. The multifactorial approach used in the developed regression scale for breast cancer 10-year prognosis increases its accuracy and reliability.
    Type of Medium: Online Resource
    ISSN: 1999-8627 , 1994-4098
    URL: Issue
    URL: Article
    DOI: 10.17650/1994-4098-2023-19-1
    DOI: 10.17650/1994-4098-2023-19-1-56-68
    Language: Unknown
    Publisher: Publishing House ABV Press
    Publication Date: 2023
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  • 7
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    Online Resource
    Intraoperative evaluation of the resection margin with the usage of digital two-point sectorography (Faxitron PathVision)
    Publishing House ABV Press ; 2023
    In:  Tumors of female reproductive system Vol. 18, No. 4 ( 2023-04-29), p. 43-51
    Details
    In: Tumors of female reproductive system, Publishing House ABV Press, Vol. 18, No. 4 ( 2023-04-29), p. 43-51
    Abstract: 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 %).
    Type of Medium: Online Resource
    ISSN: 1999-8627 , 1994-4098
    URL: Issue
    URL: Article
    DOI: 10.17650/1994-4098-2022-18-4
    DOI: 10.17650/1994-4098-2022-18-4-43-51
    Language: Unknown
    Publisher: Publishing House ABV Press
    Publication Date: 2023
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  • 8
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    Online Resource
    Current approaches to the treatment of HER2‑positive breast cancer with brain metastases
    Publishing House ABV Press ; 2021
    In:  Tumors of female reproductive system Vol. 17, No. 1 ( 2021-06-16), p. 27-34
    Details
    In: Tumors of female reproductive system, Publishing House ABV Press, Vol. 17, No. 1 ( 2021-06-16), p. 27-34
    Abstract: The article discusses modern approaches in the treatment of HER2-positive breast cancer (BC) with brain metastases (BM).The patients are subject to multidisciplinary, comprehensive and biologically – oriented treatment, with the involvement of a neurosurgeon and a radiation therapist to make a decision considering local treatment of BM, as well as a clinical oncologist to choose systemic drug therapy. Local treatment of HER2+ BC with BM patients includes surgical treatment and/or radiotherapy. Use of targeted anti-HER2 therapy changes “biology” of the disease from aggressive to indolent.In the prospective KAMILLA trial, clinically significant antitumor activity of trastuzumab emtansine was found for the first time both in patients with HER2+ BC with BM, who were previously treated with radiotherapy, and without radiotherapy in the anamnesis, which suggests the validity of further use of trastuzumab emtansine in this category of patients.The antitumor activity of trastuzumab emtansine in patients with HER2+ BC with BM was also confirmed in preclinical models. Despite the similar drug distribution in the tissues, trastuzumab emtansine, in contrast to trastuzumab, significantly slowed the growth of metastases, causing the induction of apoptosis in HER2+ BC models with BM in mice.
    Type of Medium: Online Resource
    ISSN: 1999-8627 , 1994-4098
    URL: Issue
    URL: Article
    DOI: 10.17650/1994-4098-2021-17-1
    DOI: 10.17650/1994-4098-2021-17-1-27-34
    Language: Unknown
    Publisher: Publishing House ABV Press
    Publication Date: 2021
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  • 9
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    Online Resource
    NEW ADVANCES IN THE TREATMENT OF BREAST CANCER: THE ROLE EPOTHILONES
    Remedium, Ltd. ; 2017
    In:  Medical Council , No. 6 ( 2017-01-01), p. 72-83
    Details
    In: Medical Council, Remedium, Ltd., , No. 6 ( 2017-01-01), p. 72-83
    Type of Medium: Online Resource
    ISSN: 2079-701X
    URL: Issue
    URL: Article
    DOI: 10.21518/2079-701X-2017-6
    DOI: 10.21518/2079-701X-2017-6-72-83
    Language: Unknown
    Publisher: Remedium, Ltd.
    Publication Date: 2017
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  • 10
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    Online Resource
    NEOADJUVANT ENDOCRINE THERAPY FOR PATIENTS WITH ESTROGEN-RECEPTOR-POSITIVE BREAST CANCER
    Tomsk Cancer Research Institute ; 2018
    In:  Siberian journal of oncology Vol. 17, No. 3 ( 2018-07-04), p. 11-19
    Details
    In: Siberian journal of oncology, Tomsk Cancer Research Institute, Vol. 17, No. 3 ( 2018-07-04), p. 11-19
    Abstract: More than 70 % of patients with breast cancer have estrogen-receptor-positive tumors (ER+) and are considered hormone- sensitive. That is why a vast majority of patients with early operable  tumors receive adjuvant endocrine therapy. Patients with metastatic  ER+ breast cancer also receive hormone therapy as first-line  treatment. Patients with ER+/PR+ locally advanced breast cancer  including potentially operable cases (cT2N1, cT3N0M0) are still a  subject to neoadjuvant chemotherapy in most of the oncology  centers in Russia and worldwide. More than 10 years ago, several  trials evaluating the efficacy of neoadjuvant endocrine therapy were  conducted in the Petrov Research Institute of Oncology (aromatase  inhibitors vs tamoxifen, neoadjuvant endocrine therapy vs  neoadjuvant chemotherapy, etc.) The primary endpoint was the  evaluation of pathologic complete/partial response to therapy and  the frequency of breast-conserving surgeries following neoadjuvant  treatment. We now represent 10-year long-term follow-up data on  comparison of neoadjuvant chemotherapy with neoadjuvant  endocrine therapy after retrospective determination of IHC- phenotypes of 239 patients with ER+ breast cancer. The study  results show tendency to better 10-year disease-free survival in  patients with luminal-A breast cancer who received endocrine  therapy compared to neoadjuvant chemotherapy (72.8 % vs 53.9  %, respectively, p=0.062) There were no statistically significant  differences in DFS rates among patients with the luminal B breast  cancer subtype (41 % vs 40 %) The discovery of biomarkers of  potential resistance to endocrine therapy (cycline-dependant kinase  activity [cdk 4/6] , estrogenreceptor mutation [ESR1], mTOR  signaling pathway activity, co-expression of the ER and HER2neu  [ER+/ HER2neu3+] ) and ways to inhibit the activity of the resistance pathways (palbocyclib, everolimus, etc.) have expanded the  armamentarium of endocrine-therapy for not only metastatic and  locally-advanced but also operable cases of ER+ breast cancer.
    Type of Medium: Online Resource
    ISSN: 2312-3168 , 1814-4861
    URL: Issue
    URL: Article
    DOI: 10.21294/1814-4861-2018-17-3
    DOI: 10.21294/1814-4861-2018-17-3-11-19
    Language: Unknown
    Publisher: Tomsk Cancer Research Institute
    Publication Date: 2018
    detail.hit.zdb_id: 2693095-X
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    BTU Cottbus
    Wissenschaftspark Albert Einstein
    EUV Frankfurt
    TH Wildau
    FH Potsdam
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