Surgical Management of Hereditary Breast Cancer

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.

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Gene Mutations in Hereditary Breast Cancer- A Review

European Journal of Medical and Health Sciences ◽

10.24018/ejmed.2020.2.3.286 ◽

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).

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

Case Reports in Oncology ◽

10.1159/000489698 ◽

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.

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A systematic review: breast cancer susceptibility genes

E3S Web of Conferences ◽

10.1051/e3sconf/202021803039 ◽

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.

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Identification of germ-line 185delAG BRCA1 mutation among breast cancer families in Iran: An experience from northeastern Iran.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e22079 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e22079-e22079

Author(s):

Mohammad Mahdi Kooshyar ◽

Mohammad Reza Nassiri ◽

Morteza Mahdavi ◽

Mohammad Doosti ◽

Amir Reza Parizadeh

Keyword(s):

Breast Cancer ◽

Mononuclear Cells ◽

Founder Mutation ◽

Germ Line ◽

Cancer Susceptibility ◽

Brca1 Mutation ◽

Brca1 Gene ◽

Iranian Women ◽

Management Options ◽

Cancer Susceptibility Genes

e22079 Background: The present study evaluated the prevalence of 185DelAG BRCA1 mutation in the group of Iranian women breast cancer patients, or their relative with family history of breast cancer. Breast cancer is the most common malignancy in women and the leading cause of cancer death in females worldwide. BRCA1 is among the best known cancer susceptibility genes with high penetrance and have multiple cellular functions including critical roles in homologous DNA repair. Identifying gremlin BRCA mutations associated with significant cancer susceptibility has the potential to change all aspects of an individual's care, from screening to cancer treatment. The combination of breast cancer susceptibility alleles together with other risk factors may be important clinically. Methods: Subjects included in this study were thirty nine patients diagnosed with breast cancer and 29 women, from first degree relative of patients. The clinical and demographic details from these individuals were collected from medical records, pathological reports, and when needed and using a detailed questionnaire. Genomic DNA from peripheral blood mononuclear cells was extracted and analyzed by polymerase chain reaction and SSCP methods in order to finding 185DelAG founder mutation. Results: The results indicated that four patients and three healthy relatives had this founder mutation. The identification of these founder mutations facilitates mutation population screening and subsequent management options available to an individual woman including screening or prevention are then dependent on this level of assessed risk. Conclusions: Finally identifying the effective risks regarding breast cancer among Iranian women requires many works. However, a complete BRCA1 gene sequence analysis might be useful, regarding targeted cancer prevention and therapeutics.

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

Communications Biology ◽

10.1038/s42003-020-01301-9 ◽

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.

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

Breast Cancer Research and Treatment ◽

10.1007/s10549-021-06328-y ◽

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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