scholarly journals Orbital Metastases from Breast Cancer with BRCA2 Mutation: A Case Report and Literature Review

2018 ◽  
Vol 11 (2) ◽  
pp. 360-364
Author(s):  
Emily Barber ◽  
Yung Lyou ◽  
Rita Mehta ◽  
Erin Lin ◽  
Karen Lane ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Susceptibility ◽  
Major Gene ◽  
Brca2 Mutation ◽  
The United States ◽  
Breast Cancers ◽  
Cns Metastases ◽  
Rare Presentation ◽  
Orbital Metastases ◽  
Cancer Susceptibility Genes

Breast cancer is the second leading cause of cancer-related deaths in women in the United States. Of these women, 5–10% have an inherited form of breast cancer with a mutation in a major gene, such as the breast cancer susceptibility genes 1 or 2 (BRCA1 or BRCA2). Triple negative (the most common subtype of BRCA1-associated breast cancers) and Her2-positive breast cancer patients have more frequently been observed to develop central nervous system (CNS) metastases compared to other molecular subtypes of breast cancers. However, it remains an open question if BRCA2-associated breast cancers also have a higher propensity to develop CNS metastases. Here we report a rare case of recurrent BRCA2-associated breast cancer which manifested as orbital metastases. At the time of this publication, this is one of the first cases of BRCA2-associated breast cancer to present with orbital metastases. In this article, we discuss the diagnostic challenges and review the literature regarding this rare presentation.

scholarly journals Gene Mutations in Hereditary Breast Cancer- A Review

2020 ◽  
Vol 2 (3) ◽  
Author(s):  
Pathima Fairoosa ◽  
Chamindri Witharana
Keyword(s):  
Breast Cancer ◽  
Hereditary Breast Cancer ◽  
Cancer Susceptibility ◽  
Gene Mutations ◽  
Tumour Suppressor Genes ◽  
Breast Cancers ◽  
Germline Gene ◽  
Brca1 And Brca2 ◽  
Repair Gene ◽  
Cancer Susceptibility Genes

The most prevalent form of cancer in females is breast cancer. Roughly 5%-10% of breast cancers are hereditary, and they are associated with Germline gene mutations, inherited from parents. Germline gene mutations increase the risk of developing cancer earlier in life compared to noninherited cases (sporadic cancer). BRCA1 and BRCA2 are well-studied tumour suppressor genes associated with hereditary breast cancer. Even though mutations in BRCA1 and BRCA2 are assumed to responsible the majority of hereditary breast cancers cases, many other breast cancer susceptibility genes have been identified in the last few decades. Identification of many germline mutations was possible due to advance sequencing technologies. Most of these genes are belongs to tumour suppressors and DNA damage repair gene families (DNA double-strand break repair and DNA mismatch repair). These genes play a vital role in genomic stability and cell cycle control suggesting that any alteration in these genes trigger uncontrolled growth and tumour formation. These genes are categorized according to the penetrance level, the proportion of carriers express the associated trait of the mutated gene. Mutations in high penetrance genes such as BRCA1, BRCA2, TP53, PTEN, and SKT11 greatly increase the risk of developing breast cancer. Moderate penetrance gene such as PALB2, ATM, CHEK2, BARD1, BRIP1 and low penetrance gene such as PARP4, CASP8, TOX3 confer moderate to low increase risk of developing breast cancer. Aim of this review is to summarize genes associated with hereditary breast cancer according to their penetrance level (high, moderate and low penetrance).

scholarly journals Germline Mutations in Latin American Women With Breast Cancer

2020 ◽  
Vol 6 (Supplement_1) ◽  
pp. 29-29
Author(s):  
Megan Ren ◽  
Anali Orozco ◽  
Liliana Gómez Flores-Ramos ◽  
Anaseidy Albanez ◽  
Lisa Garland ◽  
...  
Keyword(s):  
Breast Cancer ◽  
United States ◽  
Latin American ◽  
Clinical Data ◽  
Cancer Susceptibility ◽  
The United States ◽  
American Women ◽  
Cancer Susceptibility Genes ◽  
Pathogenic Mutations ◽  
Mutation Profile

PURPOSE Breast cancer is the most common form of cancer among women in Latin America. Limited health care access, late-stage diagnosis, and lack of knowledge on the mutation profile of cancer susceptibility genes in low- and middle-income country populations lead to higher mortality rates. To address this health disparity, this study analyzes the breast cancer mutation profile of women from Mexico and Guatemala. Results from this study can be used to improve breast cancer screenings in these countries and for Latin American women living in the United States. METHODS Genomic and clinical data of women with breast tumors were obtained at the Instituto Nacional de Salud Publica in Mexico and Instituto Nacional de Cancerologia in Guatemala. Mutations in known breast cancer susceptibility genes were identified using targeted sequencing and were validated by manual review in the Integrative Genomics Viewer and pathogenicity determined using online databases (ClinVar and Varsome). Finally, variants were compared with corresponding clinical data for population-wide trends. RESULTS The Mexico study identified 14% of cases with pathogenic mutations in a sample of 201 patients and the Guatemala study contained 11% pathogenic mutations in 673 patients. The most frequently mutated genes for both populations were BRCA1, BRCA2, PALB2, and TP53, with BRCA1/2 mutations accounting for 7% to 10% of all variants. Patients with pathogenic mutations were found to have a significantly younger age of onset than patients without mutations, and a family history of breast cancer was pronounced in patients with pathogenic mutations. CONCLUSION The results of this study increase our understanding of the molecular and pathologic characteristics of breast cancer in Latin American women. This list of pathogenic variants and their clinical characteristics should be used to inform cancer screening, diagnosis, and treatment in the United States and abroad.

scholarly journals A systematic review: breast cancer susceptibility genes

2020 ◽  
Vol 218 ◽  
pp. 03039
Author(s):  
ZhiLan Xie
Keyword(s):  
Breast Cancer ◽  
Cancer Susceptibility ◽  
Normal Population ◽  
Breast Cancer Susceptibility ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Cancer Susceptibility Genes ◽  
Cell Life ◽  
Dominant Female ◽  
Cell To Cell Adhesion

Breast cancer is the dominant female cancer and the top cause of cancer deaths in women among the world. The susceptible genes are critical risk factors for both hereditary and sporadic breast cancers. The incidence of carcinoma for carriers with mutated relative genes might increase in comparison with that of the normal population. These genes might be applied in breast cancer populated screening and clinical treatment, in order to improve survival of the breast cancer patients. This study concluded some genes involved in various key elementary processes in cell life, including DNA repair, cell cycle regulation, cell-to-cell adhesion and metabolism, in previous research.

scholarly journals Surgical Management of Hereditary Breast Cancer

Genes ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1371
Author(s):  
Elizabeth R. Berger ◽  
Mehra Golshan
Keyword(s):  
Breast Cancer ◽  
Surgical Management ◽  
Genetic Variant ◽  
Cancer Susceptibility ◽  
Breast Cancers ◽  
Cancer Treatments ◽  
Management Options ◽  
Cancer Susceptibility Genes ◽  
Brca 2 ◽  
Made In

The identification that breast cancer is hereditary was first described in the nineteenth century. With the identification of the BRCA1 and BRCA 2 breast/ovarian cancer susceptibility genes in the mid-1990s and the introduction of genetic testing, significant advancements have been made in tailoring surveillance, guiding decisions on medical or surgical risk reduction and cancer treatments for genetic variant carriers. This review discusses various medical and surgical management options for hereditary breast cancers.

scholarly journals Genetic and clinical landscape of breast cancers with germline BRCA1/2 variants

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Yukiko Inagaki-Kawata ◽  
Kenichi Yoshida ◽  
Nobuko Kawaguchi-Sakita ◽  
Masahiro Kawashima ◽  
Tomomi Nishimura ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Susceptibility ◽  
Clonal Selection ◽  
Breast Cancer Susceptibility ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Germline Variants ◽  
Pathogenic Variants ◽  
Cancer Susceptibility Genes ◽  
Tcga Dataset

Abstract The genetic and clinical characteristics of breast tumors with germline variants, including their association with biallelic inactivation through loss-of-heterozygosity (LOH) and second somatic mutations, remain elusive. We analyzed germline variants of 11 breast cancer susceptibility genes for 1,995 Japanese breast cancer patients, and identified 101 (5.1%) pathogenic variants, including 62 BRCA2 and 15 BRCA1 mutations. Genetic analysis of 64 BRCA1/2-mutated tumors including TCGA dataset tumors, revealed an association of biallelic inactivation with more extensive deletions, copy neutral LOH, gain with LOH and younger onset. Strikingly, TP53 and RB1 mutations were frequently observed in BRCA1- (94%) and BRCA2- (9.7%) mutated tumors with biallelic inactivation. Inactivation of TP53 and RB1 together with BRCA1 and BRCA2, respectively, involved LOH of chromosomes 17 and 13. Notably, BRCA1/2 tumors without biallelic inactivation were indistinguishable from those without germline variants. Our study highlights the heterogeneity and unique clonal selection pattern in breast cancers with germline variants.

scholarly journals Increased gene expression variability in BRCA1-associated and basal-like breast tumours

2021 ◽  
Author(s):  
George A. R. Wiggins ◽  
Michael A. Black ◽  
Anita Dunbier ◽  
Arthur E. Morley-Bunker ◽  
John F. Pearson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Susceptibility ◽  
Expression Patterns ◽  
In Situ Hybridisation ◽  
Breast Cancers ◽  
Breast Tumours ◽  
Expression Variability ◽  
Cancer Susceptibility Genes

Abstract Purpose Inherited variants in the cancer susceptibility genes, BRCA1 and BRCA2 account for up to 5% of breast cancers. Multiple gene expression studies have analysed gene expression patterns that maybe associated with BRCA12 pathogenic variant status; however, results from these studies lack consensus. These studies have focused on the differences in population means to identified genes associated with BRCA1/2-carriers with little consideration for gene expression variability, which is also under genetic control and is a feature of cellular function. Methods We measured differential gene expression variability in three of the largest familial breast cancer datasets and a 2116 breast cancer meta-cohort. Additionally, we used RNA in situ hybridisation to confirm expression variability of EN1 in an independent cohort of more than 500 breast tumours. Results BRCA1-associated breast tumours exhibited a 22.8% (95% CI 22.3–23.2) increase in transcriptome-wide gene expression variability compared to BRCAx tumours. Additionally, 40 genes were associated with BRCA1-related breast cancers that had ChIP-seq data suggestive of enriched EZH2 binding. Of these, two genes (EN1 and IGF2BP3) were significantly variable in both BRCA1-associated and basal-like breast tumours. RNA in situ analysis of EN1 supported a significant (p = 6.3 × 10−04) increase in expression variability in BRCA1-associated breast tumours. Conclusion Our novel results describe a state of increased gene expression variability in BRCA1-related and basal-like breast tumours. Furthermore, genes with increased variability may be driven by changes in DNA occupancy of epigenetic effectors. The variation in gene expression is replicable and led to the identification of novel associations between genes and disease phenotypes.

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