Double heterozygous pathogenic variants in the BRCA1 and BRCA2 genes in a patient with bilateral metachronous breast cancer

Introduction: Most breast and ovarian cancers in women are sporadic. However, five to ten percent of these individuals may have an inherited predisposition to cancer (Famorca-Tram, 2015). Women with pathogenic variants in BRCA1 are at risk of breast cancer of up to 72% and of ovarian cancer of up to 44%. Pathogenic variants of the BRCA2 gene increase the risk of breast cancer by up to 69% and of ovarian cancer by up to 25%. Risk reduction measures include: risk-reducing mastectomy, salpingo-oophorectomy, and chemoprevention. For women who do not choose any of these measures, follow-up with periodic examinations is necessary. In this work, the risk reduction measures adopted by 52 women with pathogenic variants in BRCA1 or BRCA2 in a tertiary hospital in São Paulo, Brazil, are analyzed. In addition, it was analyzed what factors could influence the risk-reducing measure adopted. Materials and methods: cross-sectional study with a sample of 52 women with pathogenic variants identified in the BRCA1 and BRCA2 genes seen at a tertiary hospital. Results: 80.8% opted for surgical management as a risk-reducing measure, with 46.2% of women having had prophylactic mastectomy, 11.5% having had bilateral salpingo-oophorectomy, and 23.1% having undergone both surgical procedures. Non-surgical management occurred in 19.2% of the cases, with 8% (3 cases) undergoing chemoprophylaxis with tamoxifen and 15.4% undergoing surveillance. Conclusion: Most patients opted for surgical intervention, with risk-reducing mastectomy being the most frequent one, followed by salpingo-oophorectomy. When testing was not requested by the geneticist, there was a greater tendency toward the surgical option.

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Analysis of pathogenic variants in BRCA1 and BRCA2 genes using next-generation sequencing in women with triple negative breast cancer from South India

Molecular Biology Reports ◽

10.1007/s11033-022-07129-2 ◽

2022 ◽

Author(s):

Taruna Rajagopal ◽

Arun Seshachalam ◽

Arunachalam Jothi ◽

Krishna Kumar Rathnam ◽

Srikanth Talluri ◽

...

Keyword(s):

Breast Cancer ◽

Next Generation Sequencing ◽

Triple Negative Breast Cancer ◽

South India ◽

Triple Negative ◽

Next Generation ◽

Brca1 And Brca2 ◽

Pathogenic Variants ◽

Brca1 And Brca2 Genes ◽

Generation Sequencing

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Double heterozygous pathogenic variants in the BRCA1 and BRCA2 genes in a patient with bilateral metachronous breast cancer: a case report

10.21203/rs.3.rs-412077/v1 ◽

2021 ◽

Author(s):

Alejandra Mampel ◽

Mayra L Sottile ◽

Silvina Denita-Juarez ◽

Ana Lía Vargas ◽

Laura M Vargas-Roig

Keyword(s):

Breast Cancer ◽

Bilateral Breast Cancer ◽

Brca2 Gene ◽

Cancer Case ◽

Brca1 And Brca2 ◽

Pathogenic Variants ◽

First Case ◽

Gene Panel Testing ◽

Brca1 And Brca2 Genes ◽

Double Heterozygosity

Abstract BackgroundDouble heterozygosity pathogenic variants in BRCA1 and BRCA2 genes are a very rare finding, particularly in non-Ashkenazi individuals. We described the first case of double heterozygosity variants in a non-Ashkenazi Argentinean woman with metachronous bilateral breast cancer. Case presentationThe proband is a 65-year-old female diagnosed with invasive ductal carcinoma in the left breast at 45 years old and invasive carcinoma in the right breast at 65 years old. She underwent a multi-gene panel testing indicating the presence of two concurrent heterozygous germline deleterious variants in BRCA1 (c.4201C>T), and BRCA2 (c.5146_5149del) genes. The patient’s son (40 years-old) was found to have the inherited pathogenic variant in BRCA2 gene. ConclusionThere are few reports of double heterozygosity variants in BRCA1 and BRCA2 genes in Latin America. The two pathogenic variants identified in our patient have not been described together so far.

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Hereditary predisposition to breast cancer and its relation to the BRCA1 and BRCA2 genes: literature review

Revista Brasileira de Análises Clínicas ◽

10.21877/2448-3877.201800615 ◽

2018 ◽

Vol 50 (1) ◽

Cited By ~ 1

Author(s):

Aline Silva Coelho ◽

Marielle Anália da Silva Santos ◽

Rosecleide Inácio Caetano ◽

Camila Fátima Piovesan ◽

Larissa Aparecida Fiuza ◽

...

Keyword(s):

Breast Cancer ◽

Literature Review ◽

Brca1 And Brca2 ◽

Hereditary Predisposition ◽

Brca1 And Brca2 Genes

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Prevalence and reclassification of BRCA1 and BRCA2 variants in a large, unselected Chinese Han breast cancer cohort

Journal of Hematology & Oncology ◽

10.1186/s13045-020-01010-0 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Yun Liu ◽

Honglian Wang ◽

Xin Wang ◽

Jiaqi Liu ◽

Junjian Li ◽

...

Keyword(s):

Breast Cancer ◽

Risk Assessment ◽

Chinese Population ◽

Functional Assay ◽

Healthy Controls ◽

Brca1 And Brca2 ◽

Chinese Han ◽

Pathogenic Variants ◽

Breast Cancer Cohort ◽

Invasive Carcinomas

AbstractAccurate interpretation of BRCA1/2 variants is critical for risk assessment and precise treatment of breast cancer (BC). Hence, the establishment of an ethnicity-based BRCA1/2 variant database of the Chinese population is of paramount importance. In this study, panel-based sequencing served to detect BRCA1/2 variants in a Chinese multicenter cohort of 21,216 BC patients and 6434 healthy controls. Overall, the percentage of subjects carrying pathogenic variants was 5.5% (1174/21,216) in BC patients and 1.1% (71/6434) in healthy controls. We identified 13 pathogenic variants as high-frequency variants that had a frequency of > 0.45‰ in BC patients (≥ 10 in 21,216 patients), none of which has been reported in Caucasians. Pathogenic BRCA1/2 variants correlated with younger onset age, higher frequencies of bilateral and triple-negative BC (TNBC), invasive carcinomas, high histological grades, and family history of BC and other cancers. Furthermore, the percentage of the subjects carrying VUS was 9.8% (2071/21,216) in BC patients and 6.9% (446/6434) in healthy controls. Based on our cohort study, we unambiguously reclassified 7 out of the 858 VUS resulting in lower VUS ratio in patients (from 9.8 to 7.9%) as well as in healthy control (from 6.9 to 5.3%). We also re-analyzed the 100 variants in 13 exons (2–5 and 15–23) of the BRCA1 genes using a functional assay (saturation genome editing; SGE). 55 of the 59 VUS had distinct status in the SGE study: 24 (43.6%) were pathogenic, and 31 (56.4%) were benign. Strong ethnicity-specific occurrences of pathogenic BRCA1/2 variants were identified in the Chinese population. Hence, the findings provide rationale and sequencing information for the implementation of BRCA1/2 variants tailored to the Chinese population into clinical risk assessment.

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Expanding the search for germline pathogenic variants for breast cancer. How far should we go and how high should we jump? The missed opportunity!

Oncology Reviews ◽

10.4081/oncol.2021.544 ◽

2021 ◽

Vol 15 (1) ◽

Author(s):

Hikmat Abdel-Razeq

Keyword(s):

Breast Cancer ◽

Brca1 And Brca2 ◽

Healthy Women ◽

Panel Testing ◽

Pathogenic Variants ◽

Gene Panel Testing ◽

History Of ◽

Risk Reducing ◽

Current Guidelines ◽

Missed Opportunity

Since the identification of BRCA1 and BRCA2 genes 3 decades ago, genetic testing and genetic counseling have become an integral part of routine clinical practice. The risk of breast cancer among carriers of germline pathogenic variants, like BRCA1 and BRCA2, is well established. Risk-reducing interventions, including bilateral mastectomies and salpingo-oophorectomies are both effective and have become more acceptable. Many researchers and professional societies view current guidelines as restrictive and may miss many at-risk women, and are calling to expand testing to include all patients with breast cancer, regardless of their personal or family history of cancer, while others are calling for wider adoption to even include all healthy women at age 30 or older. This review will address expanding testing in two directions; horizontally to include more patients, and even healthy women, and vertically to include more genes using next-generation sequencing-based multi-gene panel testing.

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