scholarly journals LOSS OF HETEROZYGOSITY IN THE BRCA1 AND BRCA2 LOCUS IN BREAST CANCER

2020 ◽  
Vol 19 (3) ◽  
pp. 97-101
Author(s):  
M. M. Tsyganov ◽  
M. K. Ibragimova ◽  
A. M. Pevzner ◽  
N. V. Litviakov
Keyword(s):  
Breast Cancer ◽  
Loss Of Heterozygosity ◽  
Objective Response ◽  
Survival Rates ◽  
Brca1 Gene ◽  
Chromosome Analysis ◽  
Response To Treatment ◽  
Rank Test ◽  
Malignant Neoplasms ◽  
Brca1 And Brca2

One of the factors of variability of malignant neoplasms is the loss of heterozygosity (LOH). The biological meaning of LOH, in relation to carcinogenesis, is associated with the inactivation of heterozygous loci of pathogenetically significant genes. Thus, the aim of this work was to study BRCA1/2 LOH in breast tumors.Material and Methods. The study included 122 patients with stage IIAIIIC breast cancer. DNA was isolated from 122 biopsy samples of tumor tissue using the QIAamp DNA mini Kit (Qiagen, Germany). To assess the status of LOH, microarray analysis was performed on high-density DNA chips from Affymetrix CytoScanTM HD Array. To process the results of microchipping, we used the Chromosome Analysis Suite 3.3 program (Affymetrix, USA).Results. The loss of heterozygosity in the BRCA1 gene was found to be associated with response to NAC. It was shown that in 59 patients LOH in the BRCA1gene was associated with an objective response to treatment (p=0.005). The presence of LOH in the studied genes was associated with a favorable prognosis. The 5-year non-metastatic survival rates were 75 % and 100 % in patients with LOH in the BRCA1 and BRCA2 genes, respectively (log-rank test: p=0.003 and p=0.05, respectively).Conclusion. The phenomenon of LOH in the BRCA1/2 genes was shown to be associated with response to NACT. BRCA1/2. Further studies are needed to evaluate the frequency of BRCA1/2 LOH after NAC for choosing and changing treatment tactics. 

scholarly journals Copy number aberrations of DNA BRCA1, NF-κB and PARP1 genes in breast cancer: assotiation with the effect of preoperation chemotherapy and prediction of the disease

2019 ◽  
pp. 10-16
Author(s):  
М.М. Цыганов ◽  
М.К. Ибрагимова ◽  
И.В. Дерюшева ◽  
Е.Ю. Гарбуков ◽  
Е.М. Слонимская ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Chromosomal Aberrations ◽  
Objective Response ◽  
Prognostic Significance ◽  
Brca1 Gene ◽  
Chromosome Analysis ◽  
Rank Test ◽  
Log Rank Test ◽  
Response To Neoadjuvant Chemotherapy

Известно, что дефицит гомологичной рекомбинации в опухолевых клетках, обусловленный, в основном, дефектом генов BRCA1/2, связан с высокой эффективностью лечения и благоприятным прогнозом заболевания. Однако наличие других альтернативных путей репарации ДНК, таких как активация генов NF-κB или PARP1, может оказывать дополнительный негативный эффект. Таким образом, целью работы явилась оценка связи аберраций числа копий ДНК генов BRCA1, NF-κB, PARP1 в опухолевой ткани молочной железы с эффектом химиотерапии и прогнозом заболевания. Материалы и методы. В исследование было включено 85 больных раком молочной железы IIA-IIIB стадии. ДНК выделяли из биопсийных образцов опухолевой ткани с использованием набора QIAamp DNA mini Kit (Qiagen, Germany). Было проведено микроматричное исследование всех образцов опухоли на ДНК-чипах высокой плотности фирмы Affymetrix CytoScanTM HD Array. Для оценки аберраций числа копий ДНК использовали программу «Chromosome Analysis Suite 3.3». Результаты. Было установлено, что наибольшая частота делеций наблюдается в гене BRCA1 (28%, 24 случая из 85), и это статистически значимо сопряжено с объективным ответом на неоадъювантную химиотерапии (p=0,02). Частота амплификации гена PARP1 в исследуемой группе больных составляет 62%, что также определяет хороший ответ на неоадъювантную химиотерапию вне зависимости от наличия аберраций других исследуемых генов. При анализе прогностической значимости аберраций генов было показано, что амплификация гена PARP1 является неблагоприятным маркером безметастатической выживаемости (log-rank test, p=0,02). Выводы. На основании полученных данных можно полагать, что аберрантное состояние генов BRCA1 и PARP1 в опухоли молочной железы, может также являться перспективным маркером эффективности химиотерапии и прогноза заболевания, что подтверждает актуальность исследования, но и требует дальнейшего детального изучения. It is well known that the presence in the tumor cells of such a phenomenon as a deficiency of homologous recombination, caused mainly by a defect in the BRCA1/2 genes, is associated with a favorable treatment effect and prognosis of the disease. But it has been established that the presence of other alternative ways of DNA repair, such as activation of the NF-κB or PARP1 genes, may have an additional negative effect. Thus, the aim of the work was to assess the association of chromosomal aberrations of the BRCA1, NF-κB, PARP1 genes in tumor breast tissue with the effect of chemotherapy and the prognosis of the disease. Materials and methods. The study included 85 patients with stage IIA - IIIB breast cancer. DNA was isolated from biopsy specimens of tumor tissue using the QIAamp DNA mini Kit (Qiagen, Germany). A microarray was studied for all tumor samples on Affymetrix CytoScanTM HD Array high-density DNA chips. To estimate the aberrations of the number of DNA copies, the program Chromosome Analysis Suite 3.3 was used. Results. It was found that the highest frequency of deletions is observed in the BRCA1 gene (28%, 24 cases out of 85), and this is statistically significantly associated with an objective response to neoadjuvant chemotherapy (p=0.02). The frequency of amplification of PARP1 in the studied group of patients is 62%, which also determines the presence of a good response to neoadjuvant chemotherapy, regardless of the presence of chromosomal aberrations of other have study genes. When analyzing the prognostic significance of gene aberrations, it was shown that PARP1 amplification is an unfavorable marker of metastatic-free survival (log-rank test, p=0.02). Conclusion. Based on the data obtained, it can be assumed that the aberrant state of the BRCA1 and PARP1 genes in a breast cancer may also be a promising marker of the effectiveness of chemotherapy and disease prognosis, which confirms the undoubted relevance of the study, but also requires further detailed study.

scholarly journals GENOME-WIDE ASSOCIATION STUDY OF LOSS OF HETEROZYGOSITY AND METASTASIS-FREE SURVIVAL IN BREAST CANCER PATIENTS

2017 ◽  
Vol 39 (2) ◽  
pp. 145-150 ◽  
Author(s):  
I V Deryusheva ◽  
M M Tsygano ◽  
E Y Garbukov ◽  
M K Ibragimova ◽  
Ju G Kzhyshkovska ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Loss Of Heterozygosity ◽  
Genome Wide Association Study ◽  
Malignant Tumors ◽  
Chromosome Analysis ◽  
Rank Test ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Genome Wide

One of the factors providing the diversity and heterogeneity of malignant tumors, particularly breast cancer, are genetic variations, due to gene polymorphism, and, especially, the phenomenon of loss of heterozygosity (LOH). It has been shown that LOH in some genes could be a good prognostic marker. Aim: To perform genome-wide study on LOH in association with metastasisfree survival in breast cancer. Materials and Methods: The study involved 68 patients with breast cancer. LOH status was detected by microarray analysis, using a high density DNA-chip CytoScanTM HD Array (Affymetrix, USA). The Chromosome Analysis Suite 3.1 (Affymetrix, USA) software was used for result processing. Results: 13,815 genes were examined, in order to detect LOH. The frequency of LOH varied from 0% to 63%. The association analysis identified four genes: EDA2R, PGK1, TAF9B and CYSLTR1 that demonstrated the presence of LOH associated with metastasis-free survival (log-rank test, p < 0.03). Conclusions: The presence of LOH in EDA2R, TAF9B, and CYSLTR1 genes is associated with metastasis-free survival in breast cancer patients, indicating their potential value as prognostic markers.

scholarly journals PARP1 inhibitors in breast cancer therapy. Mechanism of action and clinical use

2020 ◽  
Vol 16 (1) ◽  
pp. 55-64
Author(s):  
D. S. Dolgasheva ◽  
A. M. Pevzner ◽  
M. K. Ibragimova ◽  
N. V. Litvyakov ◽  
M. M. Tsyganov
Keyword(s):  
Breast Cancer ◽  
High Efficiency ◽  
Parp Inhibitor ◽  
Combined Treatment ◽  
Parp Inhibitors ◽  
Response To Treatment ◽  
Malignant Neoplasms ◽  
Brca1 And Brca2 ◽  
System A ◽  
Parp1 Inhibitors

It is known that currently PARP inhibitors are actively used in the treatment of tumors of the female reproductive system. A large number of studies have been presented demonstrating the effectiveness of PARP inhibitors in the treatment of BRCA-associated ovarian cancer. It was found that mutations in the BRCA1 and BRCA2 genes are also characteristic of breast cancer (BC). However, PARP inhibitors are rarely used in clinical practice in the treatment of BC. So far, only olaparib has become the first PARP inhibitor approved for the treatment of metastatic BC. This review presents data over the past ten years showing the high efficiency of PARP inhibitors in the treatment of malignant neoplasms of the mammary gland. In 7 of 28 studies analyzed, positive results were achieved with combined treatment with chemotherapeutic drugs and PARP inhibitors. So, for example, in two studies in the treatment of BRCA-associated BC, the response to treatment in patients was 72.5–73.2 %. Thus, PARP inhibitors are of great interest and are of practical value in the treatment of patients with BC.

scholarly journals Experience in treating BRCA-associated breast cancer. The BRCA-history of a family

2021 ◽  
pp. 34-41
Author(s):  
A. V. Sultanbaev ◽  
K. V. Menshikov ◽  
A. F. Nasretdinov ◽  
A. A. Izmailov ◽  
S. I. Musin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Standard Therapy ◽  
Therapy Group ◽  
Objective Response ◽  
Metastatic Breast ◽  
Brca1 Gene ◽  
Phase Iii ◽  
Screening Tests ◽  
Malignant Neoplasms ◽  
Malignant Tumours

Breast cancer (BC) is the most common cancer and the primary cause of cancer death. About 5 to 10% of breast cancer cases have a hereditary background. BRCA-related breast cancer is characterized by more aggressive phenotype than sporadic breast cancer. Olaparib is one of the drugs that can improve the results of treatment in this group of patients. Several phase I and II trials have shown that PARP inhibitors are effective as monotherapy in patients with metastatic breast cancer and germline BRCA1/2 mutation. A randomized, open-label, phase III trial (the OlympiAD study) comparing olaparib monotherapy and standard treatment in patients with HER2-negative mBC and a germline BRCA1/2 mutation showed hopeful results. The olaparib group registered an objective response of 59.9% compared to 28.8% in the standard therapy. A complete response was reported for 9.0% of patients in the olaparib group and 1.5% in the standard therapy group. A clinical case of treatment of a triple-negative breast cancer patient with BRCA1 c.5382insC (rs80357906) mutation is presented. There was a response to over 9-month olaparib therapy after progression on two systemic chemotherapy lines. The pedigree of the patient was also considered, her relatives with malignant tumours were identified. Screening tests were done to detect the patient’s relatives with a germline mutation in the BRCA1 gene. More thorough tests are planned to be done for early detection of malignant neoplasms in the identified healthy relatives with BRCA1 c.5382insC mutation.

scholarly journals Comparison of survival in non-metastatic inflammatory and other T4 breast cancers: a SEER population-based analysis

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dechuang Jiao ◽  
Jingyang Zhang ◽  
Jiujun Zhu ◽  
Xuhui Guo ◽  
Yue Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cox Model ◽  
Survival Rates ◽  
Tumor Grade ◽  
Population Based ◽  
Rank Test ◽  
Breast Cancers ◽  
Significant Independent Predictor ◽  
Cancer Specific Survival ◽  
7Th Edition

Abstract Background Previous studies have reported poor survival rates in inflammatory breast cancer (IBC) patients than non-inflammatory local advanced breast cancer (non-IBC) patients. However, until now, the survival rate of IBC and other T4 non-IBC (T4-non-IBC) patients remains unexplored. Methods Surveillance, Epidemiology, and End Results (SEER) database was searched to identify cases with confirmed non-metastatic IBC and T4-non-IBC who had received surgery, chemotherapy, and radiotherapy between 2010 and 2015. IBC was defined as per the American Joint Committee on Cancer (AJCC) 7th edition. Breast Cancer-Specific Survival (BCSS) was estimated by plotting the Kaplan-Meier curve and compared across groups by using the log-rank test. Cox model was constructed to determine the association between IBC and BCSS after adjusting for age, race, stage of disease, tumor grade and surgery type. Results Out of a total of 1986 patients, 37.1% had IBC and mean age was 56.6 ± 12.4. After a median follow-up time of 28 months, 3-year BCSS rate for IBC and T4-non-IBC patients was 81.4 and 81.9%, respectively (log-rank p = 0.398). The 3-year BCSS rate in HR−/HER2+ cohort was higher for IBC patients than T4-non-IBC patients (89.5% vs. 80.8%; log-rank p = 0.028), and in HR−/HER2- cohort it was significantly lower for IBC patients than T4-non-IBC patients (57.4% vs. 67.5%; log-rank p = 0.010). However, it was identical between IBC and T4-non-IBC patients in both HR+/HER2- (85.0% vs. 85.3%; log-rank p = 0.567) and HR+/HER2+ (93.6% vs. 91.0%, log-rank p = 0.510) cohorts. After adjusting for potential confounding variables, we observed that IBC is a significant independent predictor for survival of HR−/HER2+ cohort (hazards ratio [HR] = 0.442; 95% CI: 0.216–0.902; P = 0.025) and HR−/HER2- cohort (HR = 1.738; 95% CI: 1.192–2.534; P = 0.004). Conclusions Patients with IBC and T4-non-IBC had a similar BCSS in the era of modern systemic treatment. In IBC patients, the HR−/HER2+ subtype is associated with a better outcome, and HR−/HER2- subtype is associated with poorer outcomes as compared to the T4-non-IBC patients.

scholarly journals Abnormal Long Non-Coding RNAs Expression Patterns Have the Potential Ability for Predicting Survival and Treatment Response in Breast Cancer

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 996
Author(s):  
Ana Carolina Pavanelli ◽  
Flavia Rotea Mangone ◽  
Luciana R. C. Barros ◽  
Juliana Machado-Rugolo ◽  
Vera L. Capelozzi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Predictive Value ◽  
Expression Patterns ◽  
Survival Rates ◽  
In Silico Analysis ◽  
Cancer Prognosis ◽  
Response To Treatment ◽  
Breast Cancer Patients ◽  
Non Coding Rnas

Abnormal long non-coding RNAs (lncRNAs) expression has been documented to have oncogene or tumor suppressor functions in the development and progression of cancer, emerging as promising independent biomarkers for molecular cancer stratification and patients’ prognosis. Examining the relationship between lncRNAs and the survival rates in malignancies creates new scenarios for precision medicine and targeted therapy. Breast cancer (BRCA) is a heterogeneous malignancy. Despite advances in its molecular classification, there are still gaps to explain in its multifaceted presentations and a substantial lack of biomarkers that can better predict patients’ prognosis in response to different therapeutic strategies. Here, we performed a re-analysis of gene expression data generated using cDNA microarrays in a previous study of our group, aiming to identify differentially expressed lncRNAs (DELncRNAs) with a potential predictive value for response to treatment with taxanes in breast cancer patients. Results revealed 157 DELncRNAs (90 up- and 67 down-regulated). We validated these new biomarkers as having prognostic and predictive value for breast cancer using in silico analysis in public databases. Data from TCGA showed that compared to normal tissue, MIAT was up-regulated, while KCNQ1OT1, LOC100270804, and FLJ10038 were down-regulated in breast tumor tissues. KCNQ1OT1, LOC100270804, and FLJ10038 median levels were found to be significantly higher in the luminal subtype. The ROC plotter platform results showed that reduced expression of these three DElncRNAs was associated with breast cancer patients who did not respond to taxane treatment. Kaplan–Meier survival analysis revealed that a lower expression of the selected lncRNAs was significantly associated with worse relapse-free survival (RFS) in breast cancer patients. Further validation of the expression of these DELncRNAs might be helpful to better tailor breast cancer prognosis and treatment.

scholarly journals Carboplatin and vincristine chemotherapy for children with newly diagnosed progressive low-grade gliomas

1997 ◽  
Vol 2 (3) ◽  
pp. E1
Author(s):  
Roger J. Packer ◽  
Joanne Ater ◽  
Jeffrey Allen ◽  
Peter Phillips ◽  
Russell Geyer ◽  
...  
Keyword(s):  
Objective Response ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Response To Treatment ◽  
Low Grade ◽  
Significant Prognostic Factor ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Low Grade Gliomas ◽  
Response To Chemotherapy

The optimum treatment of nonresectable low-grade gliomas of childhood remains undecided. There has been increased interest in the use of chemotherapy for young children, but little information concerning the long-term efficacy of such treatment. Seventy-eight children with a mean age of 3 years (range 3 months-16 years) who had newly diagnosed, progressive low-grade gliomas were treated with combined carboplatin and vincristine chemotherapy. The patients were followed for a median of 30 months from diagnosis, with 31 patients followed for more than 3 years. Fifty-eight children had diencephalic tumors, 12 had brainstem gliomas, and three had diffuse leptomeningeal gliomas. Forty-four (56%) of 78 patients showed an objective response to treatment. Progression-free survival rates were 75 ± 6% at 2 years and 68 ± 7% at 3 years. There was no statistical difference in progression-free survival rates between children with neurofibromatosis Type 1 and those without the disease (2-year, progression-free survival 79 ± 11% vs. 75 ± 6%, respectively). The histological subtype of the tumor, its location, and its maximum response to chemotherapy did not have an impact on the duration of disease control. The only significant prognostic factor was age: children 5 years old or younger at the time of treatment had a 3-year progression-free survival rate of 74 ± 7% compared with a rate of 39 ± 21% in older children (p < 0.01). Treatment with carboplatin and vincristine is effective, especially in younger children, in controlling newly diagnosed progressive low-grade gliomas.

scholarly journals Detection of loss of heterozygosity at RAD51, RAD52, RAD54 and BRCA1 and BRCA2 loci in breast cancer: pathological correlations

1999 ◽  
Vol 81 (3) ◽  
pp. 503-509 ◽  
Author(s):  
R Gonzalez ◽  
J M Silva ◽  
G Dominguez ◽  
J M Garcia ◽  
G Martinez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Loss Of Heterozygosity ◽  
Brca1 And Brca2

scholarly journals Prevalence of BRCA1 and BRCA2 Mutations Among High-Risk Saudi Patients With Breast Cancer

2018 ◽  
pp. JGO.18.00066 ◽  
Author(s):  
Omalkhair Abulkhair ◽  
Mohammed Al Balwi ◽  
Ola Makram ◽  
Lamia Alsubaie ◽  
Medhat Faris ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Novel Mutation ◽  
Brca Mutation ◽  
Brca1 Gene ◽  
Brca1 And Brca2 ◽  
Brca1 Mutations ◽  
Brca2 Mutations ◽  
Brca1 And Brca2 Mutations ◽  
Saudi Patients

Purpose Over the past three decades, the incidence rate of breast cancer (BC) among Arab women has continually increased. However, data on the prevalence of BRCA1/2 mutations are scarce. Although the population in Saudi Arabia is at large homogeneous and consanguinity is common, especially in the central, eastern, and southern regions of the country, the prevalence of BRCA1 and BRCA2 mutations and the characteristics of BC are not well studied in the country. Methods This prospective observational study intended to determine the prevalence of BRCA1 and BRCA2 mutations and sought to examine the clinicopathologic features of BC associated with these mutations. Results Of 310 patients, 270 (87%) had no mutation. BRCA mutations were identified in 40 patients; BRCA1 mutations were found in 11% of patients, and BRCA2 mutations were found in 2% of patients. Variants of unknown significance were found in 15% of patients (45 patients). Triple-negative BC (TNBC) accounted for 86% of all patients with BC and mutations. The following three recurrent deleterious founder BRCA1 mutations were observed: c.4136_4137delCT was observed in five unrelated patients, c.5530delC was observed in three unrelated patients, and c.4524G>A mutations were observed in five unrelated patients. One novel mutation was identified in the BRCA1 gene (c.5512 dup [p.Glu1838Glyfs*42]). Conclusion Among high-risk Saudi patients with BC, BRCA1 mutations are prevalent (11%). TNBC is the most common BC subtype. Furthermore, age alone does not have a significant association with mutation, but a combination of risk factors such as age, familial history, and TNBC has a significant association with BRCA mutation.

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