Benefits and safety of multigene panel testing in patients at risk for hereditary breast cancer.

2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 16-16
Author(s):  
Nimmi S. Kapoor ◽  
Lisa D. Curcio ◽  
Carlee A. Blakemore ◽  
Amy K. Bremner ◽  
Rachel E. McFarland ◽  
...  
Keyword(s):  
Breast Cancer ◽  
At Risk ◽  
Genetic Testing ◽  
Hereditary Breast Cancer ◽  
Diagnostic Yield ◽  
Gene Panel ◽  
Panel Testing ◽  
Gene Testing ◽  
Gene Panel Testing ◽  
Patients At Risk

16 Background: Recently introduced multi-gene panel testing including BRCA1 and BRCA2 genes (BRCA1/2) for hereditary cancer risk has raised concerns with the ability to detect all deleterious BRCA1/2 mutations compared to older methods of sequentially testing BRCA1/2 separately. The purpose of this study is to evaluate rates of pathogenic BRCA1/2mutations and variants of uncertain significance (VUS) between previous restricted algorithms of genetic testing and newer approaches of multi-gene testing. Methods: Data was collected retrospectively from 966 patients who underwent genetic testing at one of three sites from a single institution. Test results were compared between patients who underwent BRCA1/2testing only (limited group, n = 629) to those who underwent multi-gene testing with 5-43 cancer-related genes (panel group, n = 337). Results: Deleterious BRCA1/2 mutations were identified in 37 patients, with equivalent rates between limited and panel groups (4.0% vs 3.6%, respectively, p = 0.86). Thirty-nine patients had a BRCA1/2 VUS, with similar rates between limited and panel groups (4.5% vs 3.3%, respectively, p = 0.49). On multivariate analysis, there was no difference in detection of either BRCA1/2 mutations or VUS between both groups. Of patients undergoing panel testing, an additional 3.9% (n = 13) had non-BRCA pathogenic mutations and 13.4% (n = 45) had non-BRCA VUSs. Mutations in PALB2, CHEK2, and ATM were the most common non-BRCA mutations identified. Conclusions: Multi-gene panel testing detects pathogenic BRCA1/2 mutations at equivalent rates as limited testing and increases the diagnostic yield. Panel testing increases the VUS rate, mainly due to non-BRCA genes. Patients at risk for hereditary breast cancer can safely benefit from upfront, more efficient, multi-gene panel testing.

scholarly journals Extended gene panel testing in lobular breast cancer

2021 ◽  
Author(s):  
Elke M. van Veen ◽  
D. Gareth Evans ◽  
Elaine F. Harkness ◽  
Helen J. Byers ◽  
Jamie M. Ellingford ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Testing ◽  
Detection Rate ◽  
Gene Panel ◽  
Lobular Breast Cancer ◽  
Germline Variants ◽  
Panel Testing ◽  
Pathogenic Variants ◽  
Gene Panel Testing ◽  
Increased Risk

AbstractPurpose: Lobular breast cancer (LBC) accounts for ~ 15% of breast cancer. Here, we studied the frequency of pathogenic germline variants (PGVs) in an extended panel of genes in women affected with LBC. Methods: 302 women with LBC and 1567 without breast cancer were tested for BRCA1/2 PGVs. A subset of 134 LBC affected women who tested negative for BRCA1/2 PGVs underwent extended screening, including: ATM, CDH1, CHEK2, NBN, PALB2, PTEN, RAD50, RAD51D, and TP53.Results: 35 PGVs were identified in the group with LBC, of which 22 were in BRCA1/2. Ten actionable PGVs were identified in additional genes (ATM(4), CDH1(1), CHEK2(1), PALB2(2) and TP53(2)). Overall, PGVs in three genes conferred a significant increased risk for LBC. Odds ratios (ORs) were: BRCA1: OR = 13.17 (95%CI 2.83–66.38; P = 0.0017), BRCA2: OR = 10.33 (95%CI 4.58–23.95; P < 0.0001); and ATM: OR = 8.01 (95%CI 2.52–29.92; P = 0.0053). We did not detect an increased risk of LBC for PALB2, CDH1 or CHEK2. Conclusion: The overall PGV detection rate was 11.59%, with similar rates of BRCA1/2 (7.28%) PGVs as for other actionable PGVs (7.46%), indicating a benefit for extended panel genetic testing in LBC. We also report a previously unrecognised association of pathogenic variants in ATM with LBC.

scholarly journals Multi gene panel testing for hereditary breast cancer - is it ready to be used?

2019 ◽  
Author(s):  
Andreea Catana ◽  
Adina Patricia Apostu ◽  
Razvan-Geo Antemie
Keyword(s):  
Breast Cancer ◽  
Hereditary Breast Cancer ◽  
Gene Panel ◽  
Variants Of Uncertain Significance ◽  
Panel Testing ◽  
Brca Genes ◽  
Prophylactic Measures ◽  
Gene Panel Testing ◽  
Uncertain Significance ◽  
High Level

Breast cancer is one of the most common malignancies and the leading cause of death among women worldwide. About 20% of breast cancers are hereditary. Approximately 30% of the mutations have remained negative after testing BRCA1/2 even in families with a Mendelian inheritance pattern for breast cancer. Additional non-BRCA genes have been identified as predisposing for breast cancer. Multi gene panel testing tries to cover and explain the BRCA negative inherited breast cancer, improving efficiency, speed and costs of the breast cancer screening. We identified 23 studies reporting results from individuals who have undergone multi gene panel testing for hereditary breast cancer and noticed a prevalence of 1-12% of non-BRCA genes, but also a high level of variants of uncertain significance. A result with a high level of variants of uncertain significance is likely to be more costly than bring benefits, as well as increase the anxiety for patients. Regarding further development of multi gene panel testing, more research is required to establish both the optimal care of patients with cancer (specific treatments like PARP inhibitors) and the management of unaffected individuals (chemoprevention and/or prophylactic surgeries). Early detection in these patients as well as prophylactic measures will significantly increase the chance of survival. Therefore, multi gene panel testing is not yet ready to be used outside clear guidelines. In conclusion, studies on additional cohorts will be needed to better define the real prevalence, penetrance and the variants of these genes, as well as to describe clear evidence-based guidelines for these patients. 

Expanded yield of multiplex panel testing in fully accrued prospective trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1525-1525
Author(s):  
Gregory Idos ◽  
Allison W. Kurian ◽  
Charite Nicolette Ricker ◽  
Duveen Sturgeon ◽  
Julie Culver ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Genetic Testing ◽  
Cancer Risk ◽  
Clinical Utility ◽  
Diagnostic Yield ◽  
Pathogenic Mutation ◽  
Gene Panel ◽  
Cancer Risk Assessment ◽  
Panel Testing ◽  
Gene Panel Testing

1525 Background: Genetic testing is a powerful tool for stratifying cancer risk. Multiplex gene panel (MGP) testing allows simultaneous analysis of multiple high- and moderate- penetrance genes. However, the diagnostic yield and clinical utility of panels remain to be further delineated. Methods: A report of a fully accrued trial (N = 2000) of patients undergoing cancer-risk assessment. Patients were enrolled in a multicenter prospective cohort study where diagnostic yield and off-target mutation detection was evaluated of a 25 gene MGP comprised of APC, ATM, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A, CHEK2, EPCAM, MLH1, MSH2, MSH6, MUTYH, NBN, PALB2, PMS2, PTEN, RAD51C, RAD51D, SMAD4, STK11, TP53. Patients were enrolled if they met standard testing guidelines or were predicted to have a ≥2.5% mutation probability by validated models. Differential diagnoses (DDx) were generated after expert clinical genetics assessment, formulating up to 8 inherited cancer syndromes ranked by estimated likelihood. Results: 1998/2000 patients had reported MGP test results. Women constituted 81% of the sample, and 40% were Hispanic; 241 tested positive for at least 1 pathogenic mutation (12.1%) and 689 (34.5%) patients carried at least 1 variant of uncertain significance. The most frequently identified mutations were in BRCA1 (17%, n = 41), BRCA2 (15%, n = 36), APC (8%, n = 19), CHEK2 (7%, n = 17), ATM (7%, n = 16). 39 patients (16%) had at least 1 pathogenic mutation in a mismatch repair (MMR) gene ( MLH1, n = 10; MSH2, n = 10; MSH6, n = 8; PMS2, n = 11). 43 individuals (18%) had MUTYH mutations – 41 were monoallelic. Among 19 patients who had mutations in APC – 16 were APC I1307K. Only 65% (n = 159) of PV results were included in the DDx, with 35% (n = 86) of mutations not clinically suspected. Conclusions: In a diverse cohort, multiplex panel use increased genetic testing yield substantially: 35% carried pathogenic mutations in unsuspected genes, suggesting a significant contribution of expanded multiplex testing to clinical cancer risk assessment. The identification of off-target mutations broadens our understanding of cancer risk and genotype-phenotype correlations. Follow-up is ongoing to assess the clinical utility of multiplex gene panel testing. Clinical trial information: NCT02324062.

scholarly journals Multi-Gene Panel Testing in Gastroenterology: Are We Ready for the Results?

2021 ◽  
pp. 1-7
Author(s):  
Flávio Pereira ◽  
Manuel R. Teixeira ◽  
Mário Dinis Ribeiro ◽  
Catarina Brandão
Keyword(s):  
Genetic Testing ◽  
Cancer Susceptibility ◽  
Familial Cancer ◽  
Short Review ◽  
Gene Panel ◽  
Inherited Cancer ◽  
Panel Testing ◽  
Gene Panel Testing ◽  
Patients At Risk ◽  
Familial Cancer Risk

Genetic testing aims to identify patients at risk for inherited cancer susceptibility. In the last decade, there was a significant increase in the request of broader panels of genes as multi-gene panel testing became widely available. However, physicians may be faced with genetic findings for which there is lack of management evidence, despite some progress in understanding their clinical relevance. In this short review, we discuss the advantages and the drawbacks related to multi-gene panel testing in the setting of a Gastrointestinal Familial Cancer Risk clinic. We also summarize the available recommendations on management of pathogenic variant carriers.

Multi-gene hereditary cancer testing among men with breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1532-1532
Author(s):  
Krystal Brown ◽  
Gregory Sampang Calip ◽  
Ryan Bernhisel ◽  
Brent Evans ◽  
Eric Thomas Rosenthal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Testing ◽  
Family History ◽  
Clinical Information ◽  
Gene Panel ◽  
Age At Diagnosis ◽  
Panel Testing ◽  
Pathogenic Variants ◽  
Gene Panel Testing ◽  
Personal Diagnosis

1532 Background: All men with a personal diagnosis of breast cancer (BC) are candidates for BRCA1/2 genetic testing, as pathogenic variants (PVs) in these genes have a known association with BC risk in both men and women. As additional genes with known BC risk in women are now routinely included in multi-gene panel testing, we evaluated the outcomes of multi-gene panel testing in a large cohort of men with BC. Methods: This analysis includes the results of commercial genetic testing for 1,358 men with BC usinga multi-gene pan-cancer panel between September 2013 and January 2017. Clinical information was obtained from provider-completed test request forms. Age at diagnosis, personal, and family history were compared for men with PVs in BRCA1/2 versus non- BRCA1/2 genes. Results: Overall, 207 (15.2%) men with BC were found to carry a PV, where 147 (10.8%) men had a PV in BRCA1/2 ( BRCA1, 0.7%; BRCA2, 10.2%) and 60 (4.4%) men had a PV in a non- BRCA1/2 gene ( CHEK2, 2.0%; ATM, 1.0%; PALB2, 1.0%; BARD1, 0.2%; NBN, 0.2%; MSH6, 0.1%; BRIP1, 0.1%; CDH1, 0.1%; CDKN2A, 0.1%; MLH1, 0.1%, TP53, 0.1%). There were no substantial differences in the median age-at-diagnosis for men without a PV (65) compared to those with a BRCA1/2 PV (66) or a non- BRCA1/2 PV (63). Prostate cancer was the most common additional malignancy among all men with BC (9.0%), with a similar incidence among men with a BRCA1/2 PV (9.2%) and a non- BRCA1/2 PV (8.3%). In addition, 1.4% of men with a BRCA1/2 PV and 3.3% of men with a non- BRCA1/2 PV had a second BC. A family history of breast and/or ovarian cancer was present in 44.4% of the testing cohort, 66.7% of men with a BRCA1/2 PV, and 48.3% of men with a non- BRCA1/2 PV. This is consistent with the relative penetrance of BRCA1/2 and other genes included here. There were no other substantial differences in family history among BRCA1/2 PV carriers versus non- BRCA1/2 PV carriers. Conclusions: Close to a third of all PVs identified here in men with BC were in a gene other than BRCA1/2. There were no obvious differences in the clinical presentation of men with a BRCA1/2 PV compared to men with a PV in another gene or no PV at all. Collectively, this suggests that multi-gene panel testing is appropriate for all men with BC, regardless of other personal or family history.

Routine use of gene panel testing in hereditary breast cancer should be performed with caution

2016 ◽  
Vol 108 ◽  
pp. 33-39 ◽  
Author(s):  
Cedric van Marcke ◽  
Anne De Leener ◽  
Martine Berlière ◽  
Miikka Vikkula ◽  
Francois P. Duhoux
Keyword(s):  
Breast Cancer ◽  
Hereditary Breast Cancer ◽  
Gene Panel ◽  
Panel Testing ◽  
Gene Panel Testing

scholarly journals Increased use of genetic health care in Iceland 2012-2017

2022 ◽  
Vol 108 (01) ◽  
pp. 11-16
Author(s):  
Hákon Björn Högnason ◽  
◽  
Vigdís Fjóla Stefánsdóttir ◽  
Eirný Þöll Þórólfsdóttir ◽  
Jón Jóhannes Jónsson ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Genetic Counselling ◽  
Single Gene ◽  
Gene Panel ◽  
Whole Genome ◽  
Panel Testing ◽  
Gene Testing ◽  
Time Period ◽  
Whole Exome ◽  
Gene Panel Testing

INTRODUCTION: A genetic counselling unit at Landspitali hospital (LSH) was established in 2006. Meanwhile, genetic testing has become an integral part of general health care. In this article we detail the outcome of genetic testing at the Department of Genetic and Molecular Medicine (DGM) at Landspitali over a five year period (2012-2017). Factors that were analyzed for the time period were: Number of patients, reason for referral, reason for genetic testing without genetic counselling and yield (proportion of positive tests) of genetic testing. METHODS: Data was analysed from two medical record databases, Shire and Saga, used by the DGM in the time period. RESULTS: The number of individuals coming for genetic counselling increased every year over the time period. Reasons for referral were cancer-related in two-thirds of cases. Other reasons for referral included various other familial disorders. Most common were autosomal dominant disorders like myotonic dystrophy, hypertrophic cardiomyopathy and autosomal recessive disorders like spinal muscular atrophy (SMA) and GM1-gangliosidosis. Most common reasons for genetic testing outside of the LSH GC unit was because of managable diseases like hemochromatosis and F5/Prothrombin-related thrombophilia. Yield of genetic testing was assessed for a) known mutation testing / carrier testing, b) single gene testing, c) gene panel testing and d) whole genome and whole exome sequencing. Known mutation testing was positive in 33% of cases and single gene testing in 46% of cases. The yield of gene panel testing for cancer was found to be lower (20%) than gene panel testing for other disorders (40%). The yield of whole exome and whole genome sequencing was 46%.

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