scholarly journals Patients’ Medical and Psychosocial Experiences After Detection of a CDH1 Variant With Multigene Panel Testing

2019 ◽  
pp. 1-14 ◽  
Author(s):  
Jada G. Hamilton ◽  
Jessica M. Long ◽  
Amanda C. Brandt ◽  
Jamie Brower ◽  
Heather Symecko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gastric Cancer ◽  
Self Report ◽  
Diffuse Gastric Cancer ◽  
Care Providers ◽  
Cancer Risks ◽  
Panel Testing ◽  
Prophylactic Gastrectomy ◽  
Multigene Panel Testing ◽  
Multigene Panel

PURPOSE Germline CDH1 pathogenic variants (PV) are associated with hereditary diffuse gastric cancer and lobular breast cancer. Although prevalence of CDH1 PV is low in the general population, detection of these variants is increasing with the growing use of multigene panel testing. Little is known about the experiences of individuals tested for CDH1 variants in the multigene panel testing era. METHODS Participants recruited from the Prospective Registry of Multiplex Testing completed a cross-sectional self-report survey regarding CDH1 genetic testing experiences, medical management, and psychosocial adaptation. RESULTS Discordance existed in interpretations of CDH1 results; 13.3% of cases had disagreements in variant classifications among commercial laboratories, and 21.4% had disagreements between participant self-report and ClinVar classification. Survey data were available from 57 individuals reporting either PV (n = 16) or variants of uncertain significance (VUS; n = 41). Those with PV were more likely than those with VUS to report receiving a recommendation for prophylactic gastrectomy, although only 40.0% of those with PV received this recommendation. Participants with VUS were less satisfied with their health care providers’ knowledge and reported less CDH1 knowledge, distress, and worry about discrimination. Participants with PV perceived greater breast cancer risks, but similar gastric cancer risks, as those with VUS. CONCLUSION Few individuals with CDH1 PV report receiving recommendations for prophylactic gastrectomy, and no differences in perceived gastric cancer risk were observed based on participants’ CDH1 results, suggesting serious unmet informational needs.

scholarly journals Multigene Panel Testing Increases the Number of Loci Associated with Gastric Cancer Predisposition

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1340 ◽  
Author(s):  
Gianluca Tedaldi ◽  
Francesca Pirini ◽  
Michela Tebaldi ◽  
Valentina Zampiga ◽  
Ilaria Cangini ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gastric Cancer ◽  
Susceptibility Genes ◽  
Cancer Predisposition ◽  
Panel Testing ◽  
Pathogenic Variants ◽  
Cancer Susceptibility Genes ◽  
Number Of Patients ◽  
Multigene Panel Testing ◽  
Multigene Panel

The main gene involved in gastric cancer (GC) predisposition is CDH1, the pathogenic variants of which are associated with diffuse-type gastric cancer (DGC) and lobular breast cancer (LBC). CDH1 only explains a fraction (10–50%) of patients suspected of DGC/LBC genetic predisposition. To identify novel susceptibility genes, thus improving the management of families at risk, we performed a multigene panel testing on selected patients. We searched for germline pathogenic variants in 94 cancer-related genes in 96 GC or LBC Italian patients with early-onset and/or family history of GC. We found CDH1 pathogenic variants in 10.4% of patients. In 11.5% of cases, we identified loss-of-function variants in BRCA1, BRCA2, PALB2, and ATM breast/ovarian cancer susceptibility genes, as well as in MSH2, PMS2, BMPR1A, PRF1, and BLM genes. In 78.1% of patients, we did not find any variants with clear-cut clinical significance; however, 37.3% of these cases harbored rare missense variants predicted to be damaging by bioinformatics tools. Multigene panel testing decreased the number of patients that would have otherwise remained genetically unexplained. Besides CDH1, our results demonstrated that GC pathogenic variants are distributed across a number of susceptibility genes and reinforced the emerging link between gastric and breast cancer predisposition.

scholarly journals CDH1 on Multigene Panel Testing: Look Before You Leap

2019 ◽  
Vol 112 (4) ◽  
pp. 330-334 ◽  
Author(s):  
Bryson W Katona ◽  
Dana Farengo Clark ◽  
Susan M Domchek
Keyword(s):  
Gastric Cancer ◽  
Risk Assessment ◽  
Cancer Risk ◽  
Clinical Decision Making ◽  
Cancer Risk Assessment ◽  
Diffuse Gastric Cancer ◽  
Cancer Syndrome ◽  
Panel Testing ◽  
Multigene Panel Testing ◽  
Multigene Panel

Abstract Multigene panel testing (MGPT) has become a critical component of cancer risk assessment in clinical practice. As technology and access improve and costs decrease, more individuals than ever are undergoing MGPT for genetic evaluation. One gene that deserves special consideration when included on MGPT is CDH1, which codes for the cell-cell adhesion protein E-cadherin. Pathogenic and likely pathogenic germline variants in CDH1 have been associated with hereditary diffuse gastric cancer syndrome, and in highly penetrant families, testing for these variants is critical for proper risk management. However, recent data demonstrated that gastric cancer penetrance in unselected CDH1 carriers may be lower than expected. Further complicating matters are the lack of effective screening strategies for gastric cancer and recommendation for risk-reducing total gastrectomy in CDH1 carriers. Therefore, the discovery of an unexpected pathogenic or likely pathogenic CDH1 variant on multigene panel testing, when testing for CDH1 would not normally be considered based on personal or family history alone, creates dilemmas for both patients and providers. In this commentary, we highlight the potential for unexpected CDH1 variants on MGPT, outline the uncertainties associated with these variants, and emphasize the importance of pretest counseling regarding the potential for an unexpected CDH1 variant. Although CDH1 testing is often important for clinical decision-making, individuals and providers need to be aware of the potential for an unexpected CDH1 variant when CDH1 is included on MGPT for cancer risk assessment.

scholarly journals Multigene Panel Testing Provides a New Perspective on Lynch Syndrome

2017 ◽  
Vol 35 (22) ◽  
pp. 2568-2575 ◽  
Author(s):  
Carin R. Espenschied ◽  
Holly LaDuca ◽  
Shuwei Li ◽  
Rachel McFarland ◽  
Chia-Ling Gau ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endometrial Cancer ◽  
Lynch Syndrome ◽  
Population Based ◽  
Brca1 And Brca2 ◽  
Panel Testing ◽  
Multigene Panel Testing ◽  
New Perspective ◽  
Testing Criteria ◽  
Multigene Panel

Purpose Most existing literature describes Lynch syndrome (LS) as a hereditary syndrome leading to high risks of colorectal cancer (CRC) and endometrial cancer mainly as a result of mutations in MLH1 and MSH2. Most of these studies were performed on cohorts with disease suggestive of hereditary CRC and population-based CRC and endometrial cancer cohorts, possibly biasing results. We aimed to describe a large cohort of mismatch repair (MMR) mutation carriers ascertained through multigene panel testing, evaluate their phenotype, and compare the results with those of previous studies. Methods We retrospectively reviewed clinical histories of patients who had multigene panel testing, including the MMR and EPCAM genes, between March 2012 and June 2015 (N = 34,981) and performed a series of statistical comparisons. Results Overall, MSH6 mutations were most frequent, followed by PMS2, MSH2, MLH1, and EPCAM mutations, respectively. Of 528 patients who had MMR mutations, 63 (11.9%) had breast cancer only and 144 (27.3%) had CRC only. When comparing those with breast cancer only to those with CRC only, MSH6 and PMS2 mutations were more frequent than MLH1 and MSH2 mutations ( P = 2.3 × 10−5). Of the 528 patients, 22.2% met BRCA1 and BRCA2 ( BRCA1/2) testing criteria and not LS criteria, and 5.1% met neither BRCA1/2 nor LS testing criteria. MSH6 and PMS2 mutations were more frequent than MLH1 and MSH2 mutations among patients who met BRCA1/2 testing criteria but did not meet LS testing criteria ( P = 4.3 × 10−7). Conclusion These results provide a new perspective on LS and suggest that individuals with MSH6 and PMS2 mutations may present with a hereditary breast and ovarian cancer phenotype. These data also highlight the limitations of current testing criteria in identifying these patients, as well as the need for further investigation of cancer risks in patients with MMR mutations.

scholarly journals Loss-of-function variants in CTNNA1 detected on multigene panel testing in individuals with gastric or breast cancer

2020 ◽  
Vol 22 (5) ◽  
pp. 840-846 ◽  
Author(s):  
Dana Farengo Clark ◽  
Scott T. Michalski ◽  
Rashmi Tondon ◽  
Bita Nehoray ◽  
Jessica Ebrahimzadeh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Loss Of Function ◽  
Panel Testing ◽  
Multigene Panel Testing ◽  
Multigene Panel

New insights into the performance of multigene panel testing: Two novel nonsense variants in BRIP1 and TP53 in a young woman with breast cancer

2018 ◽  
Vol 228-229 ◽  
pp. 1-4 ◽  
Author(s):  
Verónica Castillo-Guardiola ◽  
M Desamparados Sarabia-Meseguer ◽  
Miguel Marín-Vera ◽  
Ana Isabel Sánchez-Bermúdez ◽  
José Luis Alonso-Romero ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Young Woman ◽  
Panel Testing ◽  
Multigene Panel Testing ◽  
Multigene Panel

Impact of pre-surgical germline multigene panel testing on choice of surgery for breast cancer.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. 1579-1579
Author(s):  
Elena Zarcaro ◽  
Leif W. Ellisen ◽  
Kristen M Shannon ◽  
Erica Blouch ◽  
Steven J. Isakoff
Keyword(s):  
Breast Cancer ◽  
Panel Testing ◽  
Multigene Panel Testing ◽  
Multigene Panel

scholarly journals Acceptability and outcomes of multigene panel testing among young Black breast cancer survivors

2020 ◽  
Vol 26 (10) ◽  
pp. 2112-2114
Author(s):  
Claire C. Conley ◽  
Jennifer D. Garcia ◽  
Cristi Radford ◽  
Richard R. Reich ◽  
Alvaro N. Monteiro ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Survivors ◽  
Breast Cancer Survivors ◽  
Panel Testing ◽  
Multigene Panel Testing ◽  
Multigene Panel

scholarly journals “Decoding hereditary breast cancer” benefits and questions from multigene panel testing

The Breast ◽  
2019 ◽  
Vol 45 ◽  
pp. 29-35 ◽  
Author(s):  
Chrystelle Colas ◽  
Lisa Golmard ◽  
Antoine de Pauw ◽  
Sandrine M. Caputo ◽  
Dominique Stoppa-Lyonnet
Keyword(s):  
Breast Cancer ◽  
Hereditary Breast Cancer ◽  
Panel Testing ◽  
Multigene Panel Testing ◽  
Multigene Panel

Germline pathogenic variants in cancer predisposition genes among women with invasive lobular cancer of breast.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10581-10581
Author(s):  
Siddhartha Yadav ◽  
Chunling Hu ◽  
Susan M. Domchek ◽  
Jeffrey N. Weitzel ◽  
David Goldgar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Population Based ◽  
Cancer Predisposition ◽  
Clinical Cohort ◽  
Breast Cancer Predisposition ◽  
Panel Testing ◽  
Pathogenic Variants ◽  
Predisposition Genes ◽  
Multigene Panel Testing ◽  
Multigene Panel

10581 Background: The prevalence of germline pathogenic variants (PVs) in cancer predisposition genes among women with invasive lobular breast cancer (ILC) and the risk of ILC in PV carriers is not well-defined. Methods: The study included 2,999 women with ILC and 32,544 unaffected controls from a population-based cohort; 3,796 women with ILC and 20,323 women with invasive ductal carcinoma (IDC) undergoing clinical multigene panel testing (clinical cohort); and 125,748 exome sequences from unrelated women without a cancer diagnosis in the gnomAD 3.0 dataset. Frequencies of germline PVs in breast cancer predisposition genes ( ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, PALB2, PTEN, RAD51C, RAD51D, and TP53) were compared between women with ILC and unaffected controls in both cohorts and between women with ILC and IDC in the clinical cohort. Results: The frequency of PVs in breast cancer predisposition genes among women with ILC was 6.5% in the clinical cohort and 5.2% in the population-based cohort. In case-control analyses, CDH1 and BRCA2 PVs were associated with high risks of ILC (Odds ratio (OR) > 4), and CHEK2, ATM and PALB2 PVs were associated with moderate (OR = 2-4) risks. BRCA1 PVs and CHEK2 p.Ile157Thr were not associated with clinically relevant risks (OR < 2) of ILC. PV frequencies in these genes in ILC and IDC were similar except for PV frequencies in BRCA1 and CDH1. Conclusions: The study establishes that PVs in ATM, BRCA2, CDH1, CHEK2 and PALB2 are associated with an increased risk of ILC, whereas BRCA1 PVs are not. The similar overall PV frequencies for ILC and IDC suggest that cancer histology should not influence the decision to proceed with genetic testing. While, multigene panel testing may be appropriate for women with ILC, CDH1 should be specifically discussed in the context of low prevalence and attendant gastric cancer risk.

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