scholarly journals Double heterozygous pathogenic variants in the BRCA1 and BRCA2 genes in a patient with bilateral metachronous breast cancer: a case report

2021 ◽  
Author(s):  
Alejandra Mampel ◽  
Mayra L Sottile ◽  
Silvina Denita-Juarez ◽  
Ana Lía Vargas ◽  
Laura M Vargas-Roig
Keyword(s):  
Breast Cancer ◽  
Bilateral Breast Cancer ◽  
Brca2 Gene ◽  
Cancer Case ◽  
Brca1 And Brca2 ◽  
Pathogenic Variants ◽  
First Case ◽  
Gene Panel Testing ◽  
Brca1 And Brca2 Genes ◽  
Double Heterozygosity

Abstract BackgroundDouble heterozygosity pathogenic variants in BRCA1 and BRCA2 genes are a very rare finding, particularly in non-Ashkenazi individuals. We described the first case of double heterozygosity variants in a non-Ashkenazi Argentinean woman with metachronous bilateral breast cancer. Case presentationThe proband is a 65-year-old female diagnosed with invasive ductal carcinoma in the left breast at 45 years old and invasive carcinoma in the right breast at 65 years old. She underwent a multi-gene panel testing indicating the presence of two concurrent heterozygous germline deleterious variants in BRCA1 (c.4201C>T), and BRCA2 (c.5146_5149del) genes. The patient’s son (40 years-old) was found to have the inherited pathogenic variant in BRCA2 gene. ConclusionThere are few reports of double heterozygosity variants in BRCA1 and BRCA2 genes in Latin America. The two pathogenic variants identified in our patient have not been described together so far.

scholarly journals Concurrent germline BRCA1, BRCA2, and CHEK2 pathogenic variants in hereditary breast cancer: a case series

2021 ◽  
Author(s):  
Jasmine Sukumar ◽  
Mahmoud Kassem ◽  
Doreen Agnese ◽  
Robert Pilarski ◽  
Bhuvaneswari Ramaswamy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hereditary Breast Cancer ◽  
Case Series ◽  
Breast Cancers ◽  
Panel Testing ◽  
Pathogenic Variants ◽  
First Case ◽  
Gene Panel Testing ◽  
Personalized Approach ◽  
Double Heterozygosity

Abstract Background Concurrent germline (g) pathogenic variants related to hereditary breast cancer represent a rare occurrence. While double heterozygosity in gBRCA1 and gBRCA2 has been reported in the past, herein we describe the first case of three known concurrent pathogenic variants identified in a family with a strong history of breast cancer. Case presentation The proband is a 55-year-old female diagnosed with synchronous bilateral breast cancers. She underwent a multi-gene panel testing indicating the presence of 3 concurrent heterozygous germline deleterious variants in BRCA1 (c.181T > G), BRCA2 (c.4398_4402delACATT), and CHEK2 (1100delC). The patient’s two daughters (34 and 29 years-old) were found to be transheterozygous for inherited pathogenic variants in BRCA1 (c.181T > G) and CHEK2 (1100delC) genes. Conclusion The cancer risk and phenotypic manifestations associated with transheterozygous or multiple concurrent deleterious germline variants in hereditary breast cancer requires further investigation. A personalized approach to counseling, screening, and risk reduction should be undertaken for these individuals.

scholarly journals 167P Role of the multi-gene panel testing for detection of pathogenic variants in patients with hereditary bilateral breast cancer

2021 ◽  
Vol 32 ◽  
pp. S432-S433
Author(s):  
C. Filorizzo ◽  
D. Fanale ◽  
L. Incorvaia ◽  
N. Barraco ◽  
M. Bono ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bilateral Breast Cancer ◽  
Gene Panel ◽  
Panel Testing ◽  
Pathogenic Variants ◽  
Gene Panel Testing

scholarly journals Expanding the search for germline pathogenic variants for breast cancer. How far should we go and how high should we jump? The missed opportunity!

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Hikmat Abdel-Razeq
Keyword(s):  
Breast Cancer ◽  
Brca1 And Brca2 ◽  
Healthy Women ◽  
Panel Testing ◽  
Pathogenic Variants ◽  
Gene Panel Testing ◽  
History Of ◽  
Risk Reducing ◽  
Current Guidelines ◽  
Missed Opportunity

Since the identification of BRCA1 and BRCA2 genes 3 decades ago, genetic testing and genetic counseling have become an integral part of routine clinical practice. The risk of breast cancer among carriers of germline pathogenic variants, like BRCA1 and BRCA2, is well established. Risk-reducing interventions, including bilateral mastectomies and salpingo-oophorectomies are both effective and have become more acceptable. Many researchers and professional societies view current guidelines as restrictive and may miss many at-risk women, and are calling to expand testing to include all patients with breast cancer, regardless of their personal or family history of cancer, while others are calling for wider adoption to even include all healthy women at age 30 or older. This review will address expanding testing in two directions; horizontally to include more patients, and even healthy women, and vertically to include more genes using next-generation sequencing-based multi-gene panel testing.

A case of familial breast cancer with double heterozygosity for BRCA1 and BRCA2 genes

Breast Cancer ◽  
2012 ◽  
Vol 22 (5) ◽  
pp. 557-561 ◽  
Author(s):  
Tadashi Nomizu ◽  
Masami Matsuzaki ◽  
Naoto Katagata ◽  
Yusuke Kobayashi ◽  
Takeshi Sakuma ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Familial Breast Cancer ◽  
Brca1 And Brca2 ◽  
Brca1 And Brca2 Genes ◽  
Double Heterozygosity

scholarly journals Mutations of the BRCA1 and BRCA2 Genes in Danish Patients Diagnosed at Young Age with Multi-Centric or Bilateral Breast Cancer

1999 ◽  
Vol 15 (1-3) ◽  
pp. 94-94
Author(s):  
J. T. Bergthorsson ◽  
K. Winther ◽  
K. Fenger ◽  
A. Niebuhr ◽  
S. Klausen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bilateral Breast Cancer ◽  
Young Age ◽  
Brca1 And Brca2 ◽  
Brca1 And Brca2 Genes

scholarly journals Characteristics of BRCA-associated breast cancer in the population of the Russian Federation

2021 ◽  
Author(s):  
EI Novikova ◽  
EA Kudinova ◽  
VK Bozhenko ◽  
VA Solodkiy
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Russian Federation ◽  
False Negative ◽  
Brca2 Gene ◽  
Breast Cancer Patients ◽  
Brca1 And Brca2 ◽  
Coding Regions ◽  
Brca1 And Brca2 Genes ◽  
The Russian Federation

"Standard" diagnostic panels allow identification of only a few of BRCA1 and BRCA2 gene mutations most common in a population. Therefore, tests relying on such panels may return false negative results, since the coding regions of these genes may have other defects. For breast cancer (BC) patients, false negative test results may translate into selection of inadequate therapy by their doctors. This study aimed to identify the features of BRCA-associated breast cancer in the population of the Russian Federation. The study included breast cancer patients (n = 4440). At the first stage, all patients were screened for the eight most common BRCA1 and BRCA2 genes mutations with the help of real-time PCR. Next, patients that exhibited clinical signs of a hereditary disease (CSHD) in the absence of common mutations (n = 290) had the entire coding regions of BRCA1 and BRCA2 genes studied with next generation sequencing (NGS). "Standard" mutations in the BRCA1 and BRCA2 genes were identified in 169 (3.8%) cases. In the CSHD group, such mutations were revealed in 15.4% of cases. NGS uncovered 33 rare pathogenic BRCA1 and BRCA2 gene mutations in 40 out of 290 breast cancer patients (13.8%). It was concluded that among the residents of the Russian Federation, the range of pathogenic variants of BRCA-associated breast cancer is wide, and it stretches beyond the mutations considered by the "standard" diagnostic panels. Analysis of the entire coding regions of BRCA1 and BRCA2 genes allows increasing efficiency of detection of germline mutations in breast cancer patients at least twofold.

scholarly journals Analysis of variators in the brca1 and brca2 genes by ngs in patients from central brazil with suspected hboc syndrome: a new pathogenic variant identified

Mastology ◽  
2020 ◽  
Vol 30 (Suppl 1) ◽  
Author(s):  
Rebeca Mota Goveia ◽  
Paula Francinete Faustino da Silva ◽  
Thais Bomfim Teixeira ◽  
Ruffo de Freitas ◽  
Elisângela de Paula Silveira Lacerda
Keyword(s):  
At Risk ◽  
In Silico ◽  
Brca2 Gene ◽  
Brca1 Gene ◽  
Published Data ◽  
Brca1 And Brca2 ◽  
Pathogenic Potential ◽  
Pathogenic Variants ◽  
Brca1 And Brca2 Genes ◽  
Patients At Risk

About 10‒15% of breast cancer cases are due to deleterious germ changes, more than half of which are located in the BRCA1 or BRCA2 genes. The screening of variants in these genes for patients at risk brings benefits for better clinical management of the patient as well as for the prevention of disease recurrences both in the proband and in their relatives. The profile of genetic variants is little known to the Brazilian population and, to date, there are no published data for the population of the central region of the country. This study aimed to analyze the profile of pathogenic variants (VP) and of uncertain significance (VUS) in the BRCA1 and BRCA2 genes in this population. We selected 102 patients seen at Hospital das Clínicas, Universidade Federal de Goiás, with clinical diagnosis of invasive ductal carcinoma that met the criteria of the National Comprehensive Cancer Networking 2016/2 for hereditary breast and ovarian cancer syndrome. A collection of 4mL of peripheral blood was carried out and submitted to subsequent extraction of genomic DNA, carried out using the PureLink kit (Invitrogen). The genes in question had all their exon-intron regions sequenced using the MiSeq device (Illumina) and the raw data were evaluated using the Sophia DDM software. The risk of in silico pathogenicity of the VUS was analyzed by the software POLYPHEN2, MutationTaster, SIFT, ESP5400, G1000, GnomAD. Of the total of 102 patients evaluated in this study, 22 (21.56%) had PV or VUS in the BRCA1 or BRCA2 genes. Of these, 16 patients (72.81%) had pathogenic variants, eight with PV in BRCA1 (c.5266dupC (2), c.3331_3334delCAAC, c.211A>G, c.3228_3229delAG, c.3700_3704delGTAAA, c.4484G>T and c.5305_5306ins20) and eight with PV in BRCA2 (c.156_157insAlu, c.4829_4830delTG, c.8488-1G>A, c.6405_6409delCTTAA (3), c.517-1G>A, c.2808_2811delACAA). A total of 7 patients (31.8%) presented VUS in these genes, one in the BRCA1 gene (c.179A>G) and five in the BRCA2 gene (c.280C>T, c.811G>A, 1096T>G, 1441A>G and c.5270A>G) of which only the variant c.1441A>G had low pathogenic potential in silico. A new PV still not described in the literature was also identified, variant c.5305_5306ins20 in the BRCA1 gene. These data suggest that all patients at risk in this population should be evaluated for PV or VUS in the BRCA1 and BRCA2 genes since the presence of these variants can help in the patient's prognosis and disease prevention.

scholarly journals Breast and ovarian cancer risk reduction options for women with pathogenic variables in the brca1 and brca2 genes

Mastology ◽  
2020 ◽  
Vol 30 (Suppl 1) ◽  
Author(s):  
Sandro Vinícius Machado Melo ◽  
Thamyse Fernanda de Sa Dassie ◽  
Felipe Eduardo Martins de Andrade ◽  
Erica Maria Monteiro Santos ◽  
Benedito Mauro Rossi
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Risk Reduction ◽  
Surgical Management ◽  
Tertiary Hospital ◽  
Brca1 And Brca2 ◽  
Pathogenic Variants ◽  
Brca1 And Brca2 Genes ◽  
Risk Reduction Measures ◽  
Risk Reducing

Introduction: Most breast and ovarian cancers in women are sporadic. However, five to ten percent of these individuals may have an inherited predisposition to cancer (Famorca-Tram, 2015). Women with pathogenic variants in BRCA1 are at risk of breast cancer of up to 72% and of ovarian cancer of up to 44%. Pathogenic variants of the BRCA2 gene increase the risk of breast cancer by up to 69% and of ovarian cancer by up to 25%. Risk reduction measures include: risk-reducing mastectomy, salpingo-oophorectomy, and chemoprevention. For women who do not choose any of these measures, follow-up with periodic examinations is necessary. In this work, the risk reduction measures adopted by 52 women with pathogenic variants in BRCA1 or BRCA2 in a tertiary hospital in São Paulo, Brazil, are analyzed. In addition, it was analyzed what factors could influence the risk-reducing measure adopted. Materials and methods: cross-sectional study with a sample of 52 women with pathogenic variants identified in the BRCA1 and BRCA2 genes seen at a tertiary hospital. Results: 80.8% opted for surgical management as a risk-reducing measure, with 46.2% of women having had prophylactic mastectomy, 11.5% having had bilateral salpingo-oophorectomy, and 23.1% having undergone both surgical procedures. Non-surgical management occurred in 19.2% of the cases, with 8% (3 cases) undergoing chemoprophylaxis with tamoxifen and 15.4% undergoing surveillance. Conclusion: Most patients opted for surgical intervention, with risk-reducing mastectomy being the most frequent one, followed by salpingo-oophorectomy. When testing was not requested by the geneticist, there was a greater tendency toward the surgical option.

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