Hereditary breast and ovarian cancer (HBOC): review of its molecular characteristics, screening, treatment, and prognosis

Cancer Management ◽

Number Of Patients ◽

The Impact

Abstract Breast cancer is a common cancer affecting a large number of patients. Notably, 5–10% of all breast cancer patients are genetically predisposed to cancers. Although the most common breast cancer susceptibility genes are BRCA1 and BRCA2, which are also associated with the risk of developing ovarian and pancreatic cancer, advances in next-generation sequencing (NGS) analysis technology enabled the discovery of several non-BRCA genes responsible for breast and ovarian cancers. Studies on hereditary breast and ovarian cancer (HBOC) involve not only determining the predisposition to developing cancer, but also considering the current treatment for breast cancer, prevention of next cancer, risk diagnosis, and adoption of protective measures for relatives. We present a comprehensive review of HBOC, which will be a useful resource in the clinical setting. Many hereditary tumors, including HBOC, are syndromes characterized by the development of different types of cancer in succession. Taking advantage of knowing predisposition of susceptibility to cancer, it is important to continue and update cancer management protocols, which includes the adoption of preventive measures, countermeasures, and treatments, to accurately assess and prevent the impact of cancer on the quality of life of the next generation of patients.

Clinical Implications of the Breast Cancer Susceptibility Genes BRCA1 and BRCA2

Women s Health ◽

10.1517/17455057.1.1.027 ◽

2005 ◽

Vol 1 (1) ◽

pp. 27-34

Author(s):

Steven A Narod

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Cancer Susceptibility ◽

Cancer Chemoprevention ◽

Breast Cancer Susceptibility ◽

High Risk Population ◽

Clinical Genetics ◽

Brca1 And Brca2 ◽

Cancer Susceptibility Genes

Genetic testing for BRCA1 and BRCA2 mutations has become an important part of the practice of medical oncology and clinical genetics over the past decade. Increasing numbers of women are requesting a genetic test so that they may better understand their personal risks of breast and ovarian cancer, and so that they may take appropriate measures to reduce the risk. Several of the risk factors can be modified, including breastfeeding and the use of oral contraceptives. A significant number of women opt for preventive mastectomy or oophorectomy, which will dramatically reduce the risks of breast and ovarian cancer. Chemoprevention with tamoxifen is still uncommon, largely due to women's fears of the side effects of the drug. A number of studies have shown that magnetic resonance imaging is superior to conventional mammography in terms of the early detection of breast cancer in the high-risk population. This article explores what is known about assessing genetic risk and the evidence supporting a range of preventive strategies.

Abstract P2-06-04: The power of next generation sequencing in the detection of breast and ovarian cancer susceptibility genes other thanBRCA

10.1158/1538-7445.sabcs15-p2-06-04 ◽

2016 ◽

Author(s):

M Eliade ◽

J Skrypski ◽

A Baurand ◽

C Jacquot ◽

G Bertolone ◽

...

Keyword(s):

Ovarian Cancer ◽

Next Generation Sequencing ◽

Cancer Susceptibility ◽

Susceptibility Genes ◽

Next Generation ◽

Generation Sequencing

BRCAPRO Validation, Sensitivity of Genetic Testing of BRCA1/BRCA2, and Prevalence of Other Breast Cancer Susceptibility Genes

Journal of Clinical Oncology ◽

10.1200/jco.2002.05.121 ◽

2002 ◽

Vol 20 (11) ◽

pp. 2701-2712 ◽

Cited By ~ 332

Author(s):

Donald A. Berry ◽

Edwin S. Iversen ◽

Daniel F. Gudbjartsson ◽

Elaine H. Hiller ◽

Judy E. Garber ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Genetic Testing ◽

Cancer Susceptibility ◽

Breast Cancer Susceptibility ◽

Susceptibility Genes ◽

Brca1 And Brca2 ◽

Breast Cancer Susceptibility Genes

PURPOSE: To compare genetic test results for deleterious mutations of BRCA1 and BRCA2 with estimated probabilities of carrying such mutations; to assess sensitivity of genetic testing; and to assess the relevance of other susceptibility genes in familial breast and ovarian cancer. PATIENTS AND METHODS: Data analyzed were from six high-risk genetic counseling clinics and concern individuals from families for which at least one member was tested for mutations at BRCA1 and BRCA2. Predictions of genetic predisposition to breast and ovarian cancer for 301 individuals were made using BRCAPRO, a statistical model and software using Mendelian genetics and Bayesian updating. Model predictions were compared with the results of genetic testing. RESULTS: Among the test individuals, 126 were Ashkenazi Jewish, three were male subjects, 243 had breast cancer, 49 had ovarian cancer, 34 were unaffected, and 139 tested positive for BRCA1 mutations and 29 for BRCA2 mutations. BRCAPRO performed well: for the 150 probands with the smallest BRCAPRO carrier probabilities (average, 29.0%), the proportion testing positive was 32.7%; for the 151 probands with the largest carrier probabilities (average, 95.2%), 78.8% tested positive. Genetic testing sensitivity was estimated to be at least 85%, with false-negatives including mutations of susceptibility genes heretofore unknown. CONCLUSION: BRCAPRO is an accurate counseling tool for determining the probability of carrying mutations of BRCA1 and BRCA2. Genetic testing for BRCA1 and BRCA2 is highly sensitive, missing an estimated 15% of mutations. In the populations studied, breast cancer susceptibility genes other than BRCA1 and BRCA2 either do not exist, are rare, or are associated with low disease penetrance.

Genetic Testing to Guide Risk-Stratified Screens for Breast Cancer

Journal of Personalized Medicine ◽

10.3390/jpm9010015 ◽

2019 ◽

Vol 9 (1) ◽

pp. 15 ◽

Cited By ~ 11

Author(s):

Ava Willoughby ◽

Paul Andreassen ◽

Amanda Toland

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Genetic Testing ◽

High Risk ◽

Cancer Susceptibility ◽

Cancer Surveillance ◽

Risk Scores ◽

Uncertain Significance

Breast cancer screening modalities and guidelines continue to evolve and are increasingly based on risk factors, including genetic risk and a personal or family history of cancer. Here, we review genetic testing of high-penetrance hereditary breast and ovarian cancer genes, including BRCA1 and BRCA2, for the purpose of identifying high-risk individuals who would benefit from earlier screening and more sensitive methods such as magnetic resonance imaging. We also consider risk-based screening in the general population, including whether every woman should be genetically tested for high-risk genes and the potential use of polygenic risk scores. In addition to enabling early detection, the results of genetic screens of breast cancer susceptibility genes can be utilized to guide decision-making about when to elect prophylactic surgeries that reduce cancer risk and the choice of therapeutic options. Variants of uncertain significance, especially missense variants, are being identified during panel testing for hereditary breast and ovarian cancer. A finding of a variant of uncertain significance does not provide a basis for increased cancer surveillance or prophylactic procedures. Given that variant classification is often challenging, we also consider the role of multifactorial statistical analyses by large consortia and functional tests for this purpose.

Pleiotropy-guided transcriptome imputation from normal and tumor tissues identifies new candidate susceptibility genes for breast and ovarian cancer

10.1101/2020.04.23.043653 ◽

2020 ◽

Author(s):

Siddhartha P. Kar ◽

Daniel P. C. Considine ◽

Jonathan P. Tyrer ◽

Jasmine T. Plummer ◽

Stephanie Chen ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Prediction Models ◽

Cancer Susceptibility ◽

Breast Cancer Susceptibility ◽

Susceptibility Genes ◽

Susceptibility Loci ◽

Genomic Regions

AbstractFamilial, genome-wide association (GWAS), and sequencing studies and genetic correlation analyses have progressively unraveled the shared or pleiotropic germline genetics of breast and ovarian cancer. In this study, we aimed to leverage this shared germline genetics to improve the power of transcriptome-wide association studies (TWAS) to identify candidate breast cancer and ovarian cancer susceptibility genes. We built gene expression prediction models using the PrediXcan method in 681 breast and 295 ovarian tumors from The Cancer Genome Atlas and 211 breast and 99 ovarian normal tissue samples from the Genotype-Tissue Expression project and integrated these with GWAS meta-analysis data from the Breast Cancer Association Consortium (122,977 cases/105,974 controls) and the Ovarian Cancer Association Consortium (22,406 cases/40,941 controls). The integration was achieved through novel application of a pleiotropy-guided conditional/conjunction false discovery rate approach for the first time in the setting of a TWAS. This identified 14 new candidate breast cancer susceptibility genes spanning 11 genomic regions and 8 new candidate ovarian cancer susceptibility genes spanning 5 genomic regions at conjunction FDR < 0.05 that were > 1 Mb away from known breast and/or ovarian cancer susceptibility loci. We also identified 38 candidate breast cancer susceptibility genes and 17 candidate ovarian cancer susceptibility genes at conjunction FDR < 0.05 at known breast and/or ovarian susceptibility loci. Overlaying candidate causal risk variants identified by GWAS fine mapping onto expression prediction models for genes at known loci suggested that the association for 55% of these genes was driven by the underlying GWAS signal.SignificanceThe 22 new genes identified by our cross-cancer analysis represent promising candidates that further elucidate the role of the transcriptome in mediating germline breast and ovarian cancer risk.

A Collaborative Model to Implement Flexible, Accessible and Efficient Oncogenetic Services for Hereditary Breast and Ovarian Cancer: The C-MOnGene Study

Cancers ◽

10.3390/cancers13112729 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2729

Author(s):

Julie Lapointe ◽

Michel Dorval ◽

Jocelyne Chiquette ◽

Yann Joly ◽

Jason Robert Guertin ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Genetic Counseling ◽

Evidence Base ◽

Annual Number ◽

Patient Centered ◽

Collaborative Model ◽

Counseling And Testing ◽

Number Of Patients

Medical genetic services are facing an unprecedented demand for counseling and testing for hereditary breast and ovarian cancer (HBOC) in a context of limited resources. To help resolve this issue, a collaborative oncogenetic model was recently developed and implemented at the CHU de Québec-Université Laval; Quebec; Canada. Here, we present the protocol of the C-MOnGene (Collaborative Model in OncoGenetics) study, funded to examine the context in which the model was implemented and document the lessons that can be learned to optimize the delivery of oncogenetic services. Within three years of implementation, the model allowed researchers to double the annual number of patients seen in genetic counseling. The average number of days between genetic counseling and disclosure of test results significantly decreased. Group counseling sessions improved participants’ understanding of breast cancer risk and increased knowledge of breast cancer and genetics and a large majority of them reported to be overwhelmingly satisfied with the process. These quality and performance indicators suggest this oncogenetic model offers a flexible, patient-centered and efficient genetic counseling and testing for HBOC. By identifying the critical facilitating factors and barriers, our study will provide an evidence base for organizations interested in transitioning to an oncogenetic model integrated into oncology care; including teams that are not specialized but are trained in genetics.