Indications for BRCA1 and BRCA2 mutation testing in hereditary breast and ovarian cancer families

Breast cancer is the neoplasm with the highest incidence and mortality among women in Lithuania. The aim of the study was to determine the mutational incidence in BRCA1 and BRCA2 genes in high-risk breast and/or ovarian cancer families. After written informed consent, 36 participants from Lithuanian health science university hospital provided a blood sample for genetic analysis. Molecular diagnostics was done for 6 BRCA1and BRCA2 mutations. From 36 tested subjects for BRCA1/BRCA2 mutations. Positive test for BRCA1/BRCA2 mutations test was found in 12 (33%) cases. Most common BRCA1 mutation was 5328insC - 6 (50%) cases, other mutations: 185delAG - 1 (8,3%), 300t>6(c61G) - 4 (33,3%), 4153 del A - 1 (8,3%). All mutations were BRCA1, but none of the women were positive for the analyzed BRCA2 mutation. The mean age when the cancer was diagnosed in BRCA1 mutations group was 40.40?3.39 comparing with the group without mutations - 43.29 ?2.52. Rates of BRCA1 and BRCA2 mutation testing are increasing in young women with breast and ovarian cancer. Detected mutations in BRCA1 contribute to up to one-third of the families with breast and ovarian cancer in Lithuania.

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Abstract 2598: Predicting breast and ovarian cancer risks for BRCA1 and BRCA2 mutation carriers using polygenic risk scores

10.1158/1538-7445.am2016-2598 ◽

2016 ◽

Cited By ~ 1

Author(s):

Karoline Kuchenbaecker ◽

Jacques Simard ◽

Kenneth Offit ◽

Fergus J. Couch ◽

Douglas F. Easton ◽

...

Keyword(s):

Ovarian Cancer ◽

Brca2 Mutation ◽

Risk Scores ◽

Cancer Risks ◽

Breast And Ovarian Cancer ◽

Brca1 And Brca2 ◽

Polygenic Risk ◽

Mutation Carriers

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The Effects of Parity, Breastfeeding, and Infertility Treatment on the Risk of Hereditary Breast and Ovarian Cancer: A Review

International Journal of Gynecological Cancer ◽

10.1111/igc.0b013e3181f60d4d ◽

2010 ◽

Vol 20 (Suppl 2) ◽

pp. S31-S33 ◽

Cited By ~ 10

Author(s):

Ami Fishman

Keyword(s):

Ovarian Cancer ◽

Brca Mutation ◽

Brca2 Mutation ◽

Infertility Treatment ◽

Accurate Information ◽

Ovarian Cancer Risk ◽

Breast And Ovarian Cancer ◽

Brca1 And Brca2 ◽

Mutation Carriers ◽

Risk Of Cancer

Knowledge of the potential association of parity, breastfeeding, and infertility treatment on breast and ovarian cancer risk for BRCA1 and BRCA2 mutation carriers is important and should be a crucial part of genetic counseling. The discussion of parity and clinical management of infertility in these women is complex, and patient preferences should be considered. Ideally, these preferences should be informed by accurate information on the risks and benefits of the interventions considered. However, this important subject has been investigated in a relatively small number of studies, thus, the existing data remain somewhat limited, and the estimated risk of cancer in BRCA mutation carriers is imprecise.

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Parity and the risk of breast and ovarian cancer in BRCA1 and BRCA2 mutation carriers

Breast Cancer Research and Treatment ◽

10.1007/s10549-009-0394-1 ◽

2009 ◽

Vol 119 (1) ◽

pp. 221-232 ◽

Cited By ~ 42

Author(s):

Roger L. Milne ◽

Ana Osorio ◽

Teresa Ramón y Cajal ◽

Montserrat Baiget ◽

Adriana Lasa ◽

...

Keyword(s):

Ovarian Cancer ◽

Brca2 Mutation ◽

Breast And Ovarian Cancer ◽

Brca1 And Brca2 ◽

Mutation Carriers

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Modifiers of breast and ovarian cancer risks for BRCA1 and BRCA2 mutation carriers

Endocrine Related Cancer ◽

10.1530/erc-16-0277 ◽

2016 ◽

Vol 23 (10) ◽

pp. T69-T84 ◽

Cited By ~ 29

Author(s):

Roger L Milne ◽

Antonis C Antoniou

Keyword(s):

Ovarian Cancer ◽

Large Scale ◽

Brca2 Mutation ◽

Clinical Implementation ◽

Cancer Risks ◽

Breast And Ovarian Cancer ◽

Brca1 And Brca2 ◽

Modifying Factors ◽

Mutation Carriers ◽

Genetic And Environmental Factors

Pathogenic mutations inBRCA1andBRCA2are associated with high risks of breast and ovarian cancer. However, penetrance estimates for mutation carriers have been found to vary substantially between studies, and the observed differences in risk are consistent with the hypothesis that genetic and environmental factors modify cancer risks for women with these mutations. Direct evidence that this is the case has emerged in the past decade, through large-scale international collaborative efforts. Here, we describe the methodological challenges in the identification and characterisation of these risk-modifying factors, review the latest evidence on genetic and lifestyle/hormonal risk factors that modify breast and ovarian cancer risks for women withBRCA1andBRCA2mutations and outline the implications of these findings for cancer risk prediction. We also review the unresolved issues in this area of research and identify strategies of clinical implementation so that women withBRCA1andBRCA2mutations are no longer counselled on the basis of ‘average’ risk estimates.

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Retesting of women who are negative for a BRCA1 and BRCA2 mutation using a 20-gene panel

Journal of Medical Genetics ◽

10.1136/jmedgenet-2019-106403 ◽

2019 ◽

Vol 57 (6) ◽

pp. 380-384 ◽

Cited By ~ 2

Author(s):

Jordan Lerner-Ellis ◽

Victoria Sopik ◽

Andrew Wong ◽

Conxi Lázaro ◽

Steven A Narod ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Susceptibility ◽

Brca2 Mutation ◽

Pathogenic Variant ◽

Cancer Genes ◽

Breast And Ovarian Cancer ◽

Brca1 And Brca2 ◽

Variant Of Uncertain Significance ◽

Pathogenic Variants ◽

Cancer Susceptibility Genes

BackgroundThe value of retesting women who previously tested negative for a pathogenic variant (mutation) in BRCA1 and BRCA2 using an expanded panel of breast and ovarian cancer genes is unclear.MethodsWe studied 110 BRCA1/2-negative women who were retested using a panel of 20 breast and/or ovarian cancer susceptibility genes at the Advanced Molecular Diagnostics Laboratory (AMDL) at Mount Sinai Hospital in Toronto between March 2017 and March 2019. All patients had previously tested negative for BRCA pathogenic variants at the AMDL between January 2012 and March 2018 and were subsequently referred for retesting by their physician.ResultsOverall, six pathogenic variants in genes other than BRCA1 and BRCA2 were found (prevalence 5.5%). There were two pathogenic variants found in RAD51C, and one found in each of BRIP1, PALB2, PMS2 and PTEN. The prevalence of pathogenic variants was 6.5% for women affected with cancer (6 of 93), including 4.9% for women with breast cancer (4 of 82) and 22.2% for women with ovarian cancer (2 of 9). None of the 17 unaffected women had a clinically significant or pathogenic variant. There were 44 women (40%) for whom the result of the panel test was inconclusive due to the detection of a variant of uncertain significance.ConclusionsOur findings indicate that the retesting of BRCA1/2-negative individuals with an expanded panel of 20 breast and ovarian cancer genes can produce clinically relevant results, with a yield of 5.5% for pathogenic variants in genes other than BRCA1 and BRCA2.

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