Racial and Ethnic Differences in BRCA1/2 and Multigene Panel Testing Among Young Breast Cancer Patients

Jones, Tarsha; Ms, Trivedi; Jiang, Xingming; Silverman, Thomas; Underhill, Meghan L.; Wk, Chung; Kukafka, Rita; Crew, KD

doi:10.1007/s13187-019-01646-8

Cited by 24 publications

(25 citation statements)

References 21 publications

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“…In the Jones et al study, 683 mixed ethnic women underwent genetic testing; African ethnic women had majority of gene mutation with pathogenic variant in BRCA1/2, CHEK2 and ATM [ 26 ]. Asians were the next population with gene mutations, followed by Hispanics and lastly Caucasian.…”

Section: Discussionmentioning

confidence: 99%

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Clinicopathological characteristics of gene-positive breast cancer in the United Arab Emirates

et al. 2020

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Introduction Breast cancer is the most prevalent cancer in the United Arab Emirates (UAE). This is the first study to provide data on predisposition of breast cancer susceptibility genes with associated clinical and pathological aspects in the UAE. Material & methods A retrospective chart review for breast cancer patients undergoing genetic testing from 2016 to 2018. According to National Comprehensive Cancer Network (NCCN) guidelines genetic testing was offered. The analyzed data included; age, ethnicity, family cancer history, pathogenic variant, histopathology, stage, molecular subtype and proliferation. Results 309 patients underwent genetic testing with a positive result in 130 patients (11.9%) over a period of 36 months. In 34.6% pathogenic and likely pathogenic variants were identified. BRCA2 was the most common gene identified. The mean age was 42.9 years (±9.01). Positive family history was identified in 66 patients (50.7%). Majority had stage 1 or 2 disease (66.2%), invasive ductal carcinoma (81.5%) and hormone receptor positive cancer (45.3%). Conclusions This is the first study in the UAE to describe the clinical and pathological characteristics of hereditary breast cancer in a mixed ethnic group with dominant Arabic population. Further genetic studies will be required in the UAE population, as the prevalence of breast cancer continues to rise.

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Section: Discussionmentioning

confidence: 99%

“…Asians were the next population with gene mutations, followed by Hispanics and lastly Caucasian. In the Asian population variant of uncertain significance was higher compared to other ethnic groups [ 26 ]. Despite these results African women were less likely to undergo genetic counseling compared to Caucasian women [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological characteristics of gene-positive breast cancer in the United Arab Emirates

et al. 2020

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“…This slightly higher frequency in African Americans was not statistically significant but was similarly observed in a recent report by Jones et al . [ 13 ]. Though it is typically reported that closer to 20% of hereditary breast cancer cases have a high-risk, pathogenic variant in a clinically relevant gene [ 1 ], the percentage of cases in this study with such variants is lower.…”

Section: Discussionmentioning

confidence: 99%

“…Knowing that early age of onset is a hallmark of hereditary breast cancer [ 1 ], genetic risk factors may be contributing to this disparity. Interestingly, African Americans have been reported to have more variants of uncertain significance (VUSs) in clinically valid breast/ovarian cancer genes [ 10 – 13 , 15 , 16 ], which warrant further investigation using NGS gene panels. Ultimately, a complete spectrum of breast cancer risk variants needs to be defined to provide greater insight towards African American breast cancer disparities.…”

Section: Introductionmentioning

confidence: 99%

Gene panel screening for insight towards breast cancer susceptibility in different ethnicities

et al. 2020

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African American breast cancer genetics is less understood compared to European American breast cancer susceptibility. Despite the many advantages of gene panel screening, studies investigating African American inherited breast cancer risk and comparing variant contributions between ethnicities are infrequent. Thus, 97 breast cancer-affected individuals of African and European descent from the Alabama Hereditary Cancer Cohort were screened using the research-based gene-panel, B.O.P. ( B reast, O varian, and P rostate cancer). Upon sequencing and bioinformatic processing, rare coding variants in 14 cancer susceptibility genes were categorized according to the American College of Medical Genetics guidelines and compared between ethnicities. Overall, 107 different variants were identified, the majority of which were benign/likely benign. A pathogenic/likely pathogenic variant was detected in 8.6% and 6.5% of African American and European American cases, respectively, which was not statistically significant. However, African Americans were more likely to have at least one variant of uncertain significance (VUS; p-value 0.006); they also had significantly more VUSs in BRCA1/2 compared to European Americans ( p-value 0.015). Additionally, 51.4% of African Americans and 32.3% of European Americans harbored multiple rare variants, and African Americans were more likely to have at least one VUS and one benign/likely benign variant ( p-value 0.032), as well as multiple benign/likely benign variants ( p-value 0.089). Moreover, of the 15 variants detected in multiple breast cancer cases, ATM c.2289T>C (p.F763L), a VUS, along with two likely benign variants, BRCA2 c.2926_2927delinsAT (p.S976I) and RAD51D c.251T>A (p.L84H), were determined to be associated with African American breast cancer risk when compared to ethnic-specific controls. Ultimately, B.O.P. screening provides essential insight towards the variant contributions in clinically relevant cancer susceptibility genes and differences between ethnicities, stressing the need for future research to elucidate inherited breast cancer risk.

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“…Germline genetic testing is increasingly carried out for patients with an elevated risk of hereditary diseases such as breast and ovarian cancer (Jones et al , 2019). These tests frequently yield previously-unseen and often extremely rare genetic variants, amongst which it can be difficult to identify the subsets of pathogenic and benign variants (Blazer et al , 2015).…”

Section: Introductionmentioning

confidence: 99%

MaveRegistry: a collaboration platform for multiplexed assays of variant effect

Kuang

Kishore

Rubin

et al. 2020

Preprint

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Multiplexed assays of variant effect (MAVEs) are capable of experimentally testing all possible single nucleotide or amino acid variants in selected genomic regions, generating 'variant effect maps', which provide biochemical insight and functional evidence to enable more rapid and accurate clinical interpretation of human variation. Because the international community applying MAVE approaches is growing rapidly, we developed the online MaveRegistry platform to catalyze collaboration, reduce redundant efforts, allow stakeholders to nominate targets, and enable tracking and sharing of progress on ongoing MAVE projects.

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Racial and Ethnic Differences in BRCA1/2 and Multigene Panel Testing Among Young Breast Cancer Patients

Cited by 24 publications

References 21 publications

Clinicopathological characteristics of gene-positive breast cancer in the United Arab Emirates

Clinicopathological characteristics of gene-positive breast cancer in the United Arab Emirates

Gene panel screening for insight towards breast cancer susceptibility in different ethnicities

MaveRegistry: a collaboration platform for multiplexed assays of variant effect

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