The Role of Genetic Testing in Patients With Breast Cancer

Valencia, Olivia; Samuel, Selyne; Viscusi, Rebecca K.; Riall, Taylor S.; Neumayer, Leigh; Aziz, Hassan

doi:10.1001/jamasurg.2017.0552

Cited by 127 publications

(111 citation statements)

References 17 publications

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“…In fact, the step‐by‐step process is able to select a shrinking number of women to be investigated by gene test analysis: this approach looks to be really cost‐effective, although a recent study comparing BRCA1, BRCA2, PALB2, RAD51C, RAD51D, and BRIP1 analysis performed in selected and unselected women, seems to prevent more BC and OC in the general population, without previous selection . However, our mutation rate is in line with other series based on different eligibility criteria for HBOC, as referred in a recent review where the BRCA1/2 mutation rate in early onset BC, triple negative BC, bilateral BC, and family history of BC is about 30% . It also means that direct criteria for the Hub evaluation represent a significant way to collect women who are potentially at risk for HBOC syndrome, avoiding a multistep process and saving time and important costs.…”

Section: Discussionsupporting

confidence: 80%

“…35 However, our mutation rate is in line with other series based on different eligibility criteria for HBOC, as referred in a recent review where the BRCA1/2 mutation rate in early onset BC, triple negative BC, bilateral BC, and family history of BC is about 30%. 36 It also means that direct criteria for the Hub evaluation represent a significant way to collect women who are potentially at risk for HBOC syndrome, avoiding a multistep process and saving time and important costs.…”

Section: Discussionmentioning

confidence: 99%

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A regional population‐based hereditary breast cancer screening tool in Italy: First 5‐year results

et al. 2020

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Background Up to 10% of individuals with breast cancer (BC) belong to families with hereditary syndromes. The aim of this study was to develop an instrument to identify individuals/families at high‐hereditary risk for BC and offer dedicated surveillance programs according to different risks. Methods The instrument consisted of a primary questionnaire collecting history of BC and ovarian cancer (OC). This questionnaire was applied to women enrolled in the Emilia‐Romagna Breast Cancer Screening Program. General practitioners (GPs) and specialists could propose the same questionnaire too. Women with a score of ≥ 2, were invited to complete an oncogenetic counseling. According to the Tyrer‐Cuzick evaluation, women considered at high risk were invited to involve the most representative alive individual of the family affected with BC/OC for BRCA1/2 genetic testing. Results Since January 2012 and December 2016, 660 040 women were evaluated by the regional screening program, of which 22 289 (3.5%) were invited to the Spoke evaluation, but only 5615 accepted (25.2%). Totally, also considering women sent by GPs and specialists, 11 667 were assessed and 5554 were sent to the Hub evaluation. Finally, 2342 (42.8%) women fulfilled the criteria for genetic testing, and 544 (23.2%) resulted BRCA1/2 mutation carriers. Conclusions To our knowledge, this is the first regional population‐based multistep model that is aimed to identify individuals with BRCA1/2 mutations and to offer an intensive surveillance program for hereditary‐high risk women. This tool is feasible and effective, even if more efforts must be performed to increase the acceptance of multiple assessments by the study population.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

A regional population‐based hereditary breast cancer screening tool in Italy: First 5‐year results

et al. 2020

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“…Recommendation for counseling and genetic screening for BRCA1/2 pathogenic variants is mainly based on personal and family history of breast and/or ovarian cancer, young age at disease onset, male breast cancer and multiple tumors (bilateral breast cancer or breast and ovarian cancer in the same patient) . However, BRCA testing guidelines vary by region and country . In Sweden, the Swedish Breast Cancer Group BRCA1 and BRCA2 screening criteria are used .…”

Section: Introductionmentioning

confidence: 99%

“…8 However, BRCA testing guidelines vary by region and country. 9,10 In Sweden, the Swedish Breast Cancer Group BRCA1 and BRCA2 screening criteria are used. 8 A report by Nilsson et al estimated that the Swedish BRCA testing criteria has an effectiveness of only 18% and concluded that clinical genetic testing criteria for BRCA1 and BRCA2 should be critically revised.…”

Section: Introductionmentioning

confidence: 99%

Prevalence of BRCA1 and BRCA2 pathogenic variants in a large, unselected breast cancer cohort

Wen

Eklund

et al. 2018

Intl Journal of Cancer

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Breast cancer patients with BRCA1/2-driven tumors may benefit from targeted therapy. It is not clear whether current BRCA screening guidelines are effective at identifying these patients. The purpose of our study was to evaluate the prevalence of inherited BRCA1/2 pathogenic variants in a large, clinically representative breast cancer cohort and to estimate the proportion of BRCA1/2 carriers not detected by selectively screening individuals with the highest probability of being carriers according to current clinical guidelines. The study included 5,122 unselected Swedish breast cancer patients diagnosed from 2001 to 2008. Target sequence enrichment (48.48 Fluidigm Access Arrays) and sequencing were performed (Illumina Hi-Seq 2,500 instrument, v4 chemistry). Differences in patient and tumor characteristics of BRCA1/2 carriers who were already identified as part of clinical BRCA1/2 testing routines and additional BRCA1/2 carriers found by sequencing the entire study population were compared using logistic regression models. Ninety-two of 5,099 patients with valid variant calls were identified as BRCA1/2 carriers by screening all study participants (1.8%). Only 416 study participants (8.2%) were screened as part of clinical practice, but this identified 35 out of 92 carriers (38.0%). Clinically identified carriers were younger, less likely postmenopausal and more likely to be associated with familiar ovarian cancer compared to the additional carriers identified by screening all patients. More BRCA2 (34/42, 81.0%) than BRCA1 carriers (23/50, 46%) were missed by clinical screening. In conclusion, BRCA1/2 mutation prevalence in unselected breast cancer patients was 1.8%. Six in ten BRCA carriers were not detected by selective clinical screening of individuals.

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“…Hereditary breast and ovarian cancer (HBOC) accounts for 5–10% of the total breast/ovarian cancer cases, and pathogenic variants in the high‐penetrance genes BRCA1 (MIM# 113705) and BRCA2 (MIM# 600185; BRCA1/2 ) explain about 15–20% of HBOC cases (Couch, Nathanson, & Offit, ; Shiovitz & Korde, ), although this proportion varies depending on the ascertainment criteria for BRCA1/2 testing and between ethnic groups. BRCA1/2 genetic testing is generally recommended to individuals with a personal or family history of breast/ovarian cancer, with two or more family members affected, the presence of male breast cancer and/or the presence of triple‐negative breast cancer cases, among other indicative criteria (Valencia et al, ).…”

Section: Introductionmentioning

confidence: 99%

Incorporation of semi‐quantitative analysis of splicing alterations for the clinical interpretation of variants inBRCA1andBRCA2genes

Montalban¹,

Bonache²,

Moles‐Fernández³

et al. 2019

Human Mutation

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BRCA1 and BRCA2 (BRCA1/2) genetic variants that disrupt messenger RNA splicing are commonly associated with increased risks of developing breast/ovarian cancer.The majority of splicing studies published to date rely on qualitative methodologies (i.e., Sanger sequencing), but it is necessary to incorporate semi-quantitative or quantitative approaches to accurately interpret the clinical significance of spliceogenic variants. Here, we characterize the splicing impact of 31 BRCA1/2 variants using semi-quantitative capillary electrophoresis of fluorescent amplicons (CE), Sanger sequencing and allele-specific assays. A total of 14 variants were found to disrupt splicing. Allelic-specific assays could be performed for BRCA1 c.302−1G>A and BRCA2 c.

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The Role of Genetic Testing in Patients With Breast Cancer

Cited by 127 publications

References 17 publications

A regional population‐based hereditary breast cancer screening tool in Italy: First 5‐year results

A regional population‐based hereditary breast cancer screening tool in Italy: First 5‐year results

Prevalence of BRCA1 and BRCA2 pathogenic variants in a large, unselected breast cancer cohort

Incorporation of semi‐quantitative analysis of splicing alterations for the clinical interpretation of variants inBRCA1andBRCA2genes

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