scholarly journals Germline Genetic Findings Which May Impact Therapeutic Decisions in Families with a Presumed Predisposition for Hereditary Breast and Ovarian Cancer

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2151 ◽  
Author(s):  
Carolina Velázquez ◽  
De Leeneer K. ◽  
Eva M. Esteban-Cardeñosa ◽  
Francisco Avila Cobos ◽  
Enrique Lastra ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Germline Mutation ◽  
Pathogenic Mutation ◽  
Breast And Ovarian Cancer ◽  
Brca1 And Brca2 ◽  
Therapeutic Implications ◽  
Therapeutic Decisions ◽  
The Family ◽  
Causal Variants ◽  
Index Cases

In this study, we aim to gain insight in the germline mutation spectrum of ATM, BARD1, BRIP1, ERCC4, PALB2, RAD51C and RAD51D in breast and ovarian cancer families from Spain. We have selected 180 index cases in whom a germline mutation in BRCA1 and BRCA2 was previously ruled out. The importance of disease-causing variants in these genes lies in the fact that they may have possible therapeutic implications according to clinical guidelines. All variants were assessed by combined annotation dependent depletion (CADD) for scoring their deleteriousness. In addition, we used the cancer genome interpreter to explore the implications of some variants in drug response. Finally, we compiled and evaluated the family history to assess whether carrying a pathogenic mutation was associated with age at diagnosis, tumour diversity of the pedigree and total number of cancer cases in the family. Eight unequivocal pathogenic mutations were found and another fourteen were prioritized as possible causal variants. Some of these molecular results could contribute to cancer diagnosis, treatment selection and prevention. We found a statistically significant association between tumour diversity in the family and carrying a variant with a high score predicting pathogenicity (p = 0.0003).

The prevalence of BRCA1/2 germline mutation in Chinese pan-cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13684-e13684
Author(s):  
Fei Ma ◽  
Lixi Li ◽  
Zongbi Yi ◽  
Jianming Shi ◽  
Hua Jiang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Germline Mutation ◽  
Hereditary Cancer ◽  
Cancer Risk Assessment ◽  
Founder Mutations ◽  
Breast And Ovarian Cancer ◽  
Brca1 And Brca2 ◽  
Variant Of Uncertain Significance ◽  
Pathogenic Variants ◽  
Pan Cancer

e13684 Background: Pathogenic variants in cancer predisposition genes BRCA1/2 confer susceptibility to breast and ovarian cancer and well-studied. But the characteristics of BRCA in other cancers is unknown, we identified and characterized BRCA germline variants in a large pan-cancer in China. Methods: NGS was performed on genomic DNA from 29,676 pan-cancer patients. Large fragment deletions were all verified by QPCR. We integrated guidelines of ACMG/AMP, ENIGMA and China expert consensus. Based on the in-house system, variants were interpreted one-by-one and classified into 5 grades: Benign (B), Likely Benign(LB), Variant of Uncertain significance(VUS), Likely pathogenic (LP), Pathogenic (P). Results: Among 29,676 patients, 300 BRCA1 mutations and 440 BRCA2 mutations were detected in our study. The proportion among P/LP/VUS/LB/B were 36.1%, 11.6%, 36.6%, 11.1% and 4.6%. Consistent with previous reports, the mutations spread around the whole genes. Missense and frameshift were most common types in BRCA1 (40%, 25.3%) and BRCA2 (42.3%, 29.3%). 192(25.9%) mutations were not reported in any of the databases. Among these newly reported mutations, 32 (16.7%) were classified as P, 62 (32.3%) LP and 98 (51%) VUS. Totally, 522 (1.8%) patients were identified with P/LP BRCA1/2 mutations. No founder mutations in Chinese population were defined, but BRCA1 5470_5477delATTGGGCA (I1824Dfs*3) and BRCA2 3109C > T (Q1037*) had the highest prevalence indicating the common P/LP mutations in Chinese. On the whole, BRCA-associated hereditary cancer harbored higher P/LP percent than other cancer types (11.1% vs 0.7%). Different distribution and percent were observed in BRCA1 and BRCA2, the P/LP mutations were found in double primary cancers of breast and ovary (76.9% vs 38.5%), followed by ovarian cancer (15.5% vs 6.3%), breast cancer(3.8% vs 4.0%), endometrial cancer(1.6% vs 2.4%), prostatic cancer(1.3% vs 1.9%), pancreatic cancer (0.3% vs 1.8%), biliary tract tumor (0% vs 1%), thyroid cancer (0% vs 0.9%), NSCLC(0.2% vs 0.5%) and colorectal cancer(0.08% vs 0.4%). Except for SNV/Indels, large range heterozygous deletions were found in 9 patients, including 4 (0.6%) OC, 4 (0.2%) BC and 1 NSCLC, almost all interfering with BRCA1. Conclusions: This analysis depicted a comprehensive landscape of germline BRCA1/2 variants in Chinese pan-cancer. Besides breast and ovarian cancer, lots of other cancers also harbor BRCA germline mutation, retrospective family history and hereditary cancer risk assessment needs further study.

scholarly journals A Case Report of Germline Compound Heterozygous Mutations in the BRCA1 Gene of an Ovarian and Breast Cancer Patient

2021 ◽  
Vol 22 (2) ◽  
pp. 889
Author(s):  
Ava Kwong ◽  
Cecilia Y. S. Ho ◽  
Vivian Y. Shin ◽  
Chun Hang Au ◽  
Tsun Leung Chan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Brca1 Gene ◽  
Pathogenic Mutation ◽  
Compound Heterozygous ◽  
Strong Family History ◽  
Breast And Ovarian Cancer ◽  
Pathogenic Mutations ◽  
Increased Risk ◽  
History Of

The germline carrier of the BRCA1 pathogenic mutation has been well proven to confer an increased risk of breast and ovarian cancer. Despite BRCA1 biallelic pathogenic mutations being extremely rare, they have been reported to be embryonically lethal or to cause Fanconi anemia (FA). Here we describe a patient who was a 48-year-old female identified with biallelic pathogenic mutations of the BRCA1 gene, with no or very subtle FA-features. She was diagnosed with ovarian cancer and breast cancer at the ages of 43 and 44 and had a strong family history of breast and gynecological cancers.

scholarly journals Clinical Implications of the Breast Cancer Susceptibility Genes BRCA1 and BRCA2

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 ◽  
Breast And Ovarian Cancer ◽  
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.

scholarly journals Factors influencing women’s decisions to getting tested for BRCA mutation

2018 ◽  
Vol 9 (3) ◽  
pp. 33 ◽  
Author(s):  
Suha Al-Oballi Kridli ◽  
Holly Austin
Keyword(s):  
Ovarian Cancer ◽  
Brca Mutation ◽  
Genetic Mutations ◽  
Inclusion Criteria ◽  
Breast And Ovarian Cancer ◽  
Brca1 And Brca2 ◽  
Brca Mutations ◽  
Factors Influencing ◽  
Brca1 And Brca2 Mutations ◽  
Internal And External Factors

Ovarian cancer is the leading cause of death among gynecological cancers. There are many risk factors that can increase a woman’s susceptibility to breast and ovarian cancers, some of which are modifiable.  However, non-modifiable risks for breast and ovarian cancer include the presence of genetic mutations (BRCA) increase the risk of these diseases. The purpose of this review was to identify factors, reported in the literature, known to affect women’s decision to get genetic testing for BRCA1 and BRCA2 mutations for hereditary breast and ovarian cancer. A total of 31 studies that met the inclusion criteria were included in this review. Several internal and external factors, influencing women’s decision to getting tested for BRCA mutations, were identified and explained. Implications for clinical practice were provided.

Clinical Considerations in the Management of Individuals at Risk for Hereditary Breast and Ovarian Cancer

2002 ◽  
Vol 9 (6) ◽  
pp. 457-465 ◽  
Author(s):  
Mark E. Robson
Keyword(s):  
Ovarian Cancer ◽  
At Risk ◽  
Clinical Management ◽  
Management Strategies ◽  
Breast And Ovarian Cancer ◽  
Brca1 And Brca2 ◽  
Hereditary Risk ◽  
Increased Risk ◽  
Post Test ◽  
Clinical Considerations

Background Hereditary predisposition to breast and ovarian cancer, most commonly due to germline mutations in BRCA1 and BRCA2, has been recognized for many years. The optimal clinical management of individuals with such a predisposition is not yet completely defined. Methods The current literature regarding the clinical management of individuals at risk for hereditary breast and ovarian cancer was reviewed. Results Women with germline BRCA1 or BRCA2 mutations are at substantially increased risk for breast and ovarian cancer, although the risks may not be as high as originally reported. Current surveillance options are restricted in their effectiveness by both host and tumor factors as well as limitations of the techniques. Surgical prevention options, while effective, may be complicated by physical or psychological morbidity. Nonsurgical prevention options are under development. Conclusions The ability to define women as being at hereditary risk for breast and ovarian cancer facilitates the use of specialized surveillance and prevention strategies. Genetic testing, which plays a role in defining risk, requires careful pre- and post-test counseling to discuss the limitations of testing itself and available management strategies.

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