Effect of access to germline genetic testing on pancreatic cancer precision treatment across disease stage and ethnicity.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16783-e16783
Author(s):  
Edward D. Esplin ◽  
Rebecca Truty ◽  
Shan Yang ◽  
Sarah M. Nielsen ◽  
Margaret Klint ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
African American ◽  
Genetic Testing ◽  
Family History ◽  
Germline Mutations ◽  
Disease Stage ◽  
Family History Of Cancer ◽  
History Of ◽  
History Of Cancer ◽  
Multigene Panel

e16783 Background: PARP inhibitor (PARPi) treatment was recently approved for pancreatic cancer (PaCa) patients with germline mutations in 2 DNA damage repair (DDR) genes. Despite criteria recommending germline multigene panel testing for all PaCa patients, barriers to testing remain, including among underserved populations, which limit access to precision therapies. We initiated a sponsored testing program that increases access to germline genetic testing for PaCa in two ways: 1) offering a comprehensive multigene panel, and 2) removing the barrier of cost. Here we present initial results from this program, including the diagnostic yield in patients across stages of PaCa and clinical utility of the findings. Methods: We retrospectively analyzed de-identified data from 966 PaCa patients tested on an 84 gene panel as part of the program to date. The only inclusion criterion was a willingness to participate in the sponsored program by the patient and the provider who ordered the testing. Data included likely pathogenic (LP) and pathogenic (P) mutations, disease stage and ethnicity. Results: In total, 166 (17%) patients were positive for P/LP germline mutations in 30 genes. Mutation rate by ethnicity was: Caucasian 17%, African American 12%, Hispanic 16%, Ashkenazi Jewish 20%, Asian 3%. Only 25% of patients with P/LP variants reported a family history of cancer. There was no statistical difference in mutation rates by stage (p = 0.11) [Table]. In positive patients, 83 (78%) had mutations conferring potential eligibility for DDR gene-specific precision therapies or clinical treatment trials. 28 (26%) were potentially eligible for olaparib due to BRCA1/2 mutations, 8 (7%) were potentially eligible for pembrolizumab, and 47 (44%) for PARPi clinical trials. Conclusions: This study found 8.5% of all PaCa patients tested are potentially eligible for germline-based precision therapies and/or clinical treatment trials. Of mutation positive patients, 75% did not report a family history of cancer. The positive rate was not statistically different between patients with stage I and stage IV PaCa, underscoring the recommendation to test all patients with PaCa. This program had a 1.5% increased relative uptake among African American patients compared to a standard insurance reimbursement delivery model. These data suggest reducing barriers improves PaCa patient access to genetic information that enables precision therapy. [Table: see text]

Germline mutations in Brazilian pancreatic carcinoma patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16749-e16749
Author(s):  
Livia Munhoz Rodrigues ◽  
Simone Maistro ◽  
Maria Lucia Hirata Katayama ◽  
Luiz A.Senna Leite ◽  
Joao Glasberg ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Genetic Testing ◽  
Family History ◽  
Pancreatic Carcinoma ◽  
Germline Mutations ◽  
Family History Of Cancer ◽  
First Degree Relatives ◽  
Pathogenic Variants ◽  
History Of ◽  
History Of Cancer

e16749 Background: Pancreatic cancer has the prospect of becoming the second leading cause of cancer death by 2030. The NCCN Guidelines recommend genetic testing for all patients with pancreatic cancer, however, the spectrum of germline mutations has not been extensively evaluated because recent studies with genetic testing have explored only a limited number of genes and have focused predominantly on Caucasian populations. Therefore, our objective is to evaluate the frequency and spectrum of germline mutations in unselected patients with pancreatic cancer in a multiethnic population. Methods: Patients from Instituto do Câncer do Estado de São Paulo (Brazil) with histopathological diagnosis of non-endocrine pancreatic carcinoma were included, regardless of the family history of cancer. These patients answered a life habits and family history of cancer questionnaire and supplied blood for the Next Generation Sequencing (MiSeq platform) with the TruSight Hereditary Cancer panel (Illumina), which includes 115 cancer predisposing genes. Variant analysis was performed with the VarStation, a Brazilian tool that offers post-sequencing computational support and aid for clinical interpretation. Results: To the present moment, 77 patients were evaluated. The mean age of the patients was 62 years (27-83), among whom, 13% with young age (≤50 years) and 47 women (61%). Thirty-eight patients (49%) reported cases of cancer in first-degree relatives. Regarding risk factors, 41 patients (53%) reported smoking, 19 (25%) alcohol ingestion and 20 (26%) had obesity. Seven out of 77 patients presented pathogenic variants in ATM (n = 2) , CHEK2, FANCM (n = 2) or PALB2 (n = 2) genes. Two of these patients ( CHEK2 and FANCM) had early onset pancreatic cancer (≤45 years), both denied smoking habit and family history of cancer in 1st degree relatives. Two patients, who were ATM mutation carriers, reported 1st or 2nd degree relatives with cancer and are alive after 4 and 8 years of diagnosis. Conclusions: In this unselected group of pancreatic cancer patients, 15% were young, almost half reported first-degree relatives with cancer and 9% were carriers of pathogenic variants in genes related with the homologous recombination DNA repair.

scholarly journals Self-Reported Questionnaire Detects Family History of Cancer in a Pancreatic Cancer Screening Program

2016 ◽  
Vol 26 (4) ◽  
pp. 806-813 ◽  
Author(s):  
Aimee L. Lucas ◽  
Adam Tarlecki ◽  
Kellie Van Beck ◽  
Casey Lipton ◽  
Arindam RoyChoudhury ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Screening ◽  
Family History ◽  
Screening Program ◽  
Family History Of Cancer ◽  
Pancreatic Cancer Screening ◽  
Cancer Screening Program ◽  
History Of ◽  
History Of Cancer

Germline mutations in early-onset or hereditary breast cancer from the Middle East.

2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 20-20 ◽  
Author(s):  
Makia J Marafie ◽  
Rabea Al-Temaimi ◽  
Andre Megarbane ◽  
Fahd Al-Mulla
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Middle East ◽  
Middle Eastern ◽  
Germline Mutations ◽  
Illumina Platform ◽  
Family History Of Cancer ◽  
Middle Eastern Women ◽  
History Of ◽  
History Of Cancer

20 Background: Breast cancer is the most common cancer affecting women of Middle Eastern origin. Epidemiologically, breast cancer in the Middle East clusters in families and usually affects women a decade younger than Western women. This dilemma is compounded by the lack of curated databases and ambitious studies that address the roles genetic or genomic may play in breast cancer. Methods: We have exome sequenced 60 Middle Eastern women with moderate and strong family history of cancer or young women without significant family history of cancer. DNA extracted from peripheral blood of patients and matching normal Middle Eastern women without history of familial or sporadic cancers, were subjected to whole-exome sequencing using the HiSeq 2500 Illumina platform and MLPA to map major breast cancer–activating genetic defects. Results: Several novel BRCA1/2 mutations were identified in the minority of these women. However, other complex mutations in non-BRCA1/2 genes appear to play a more subtle role in breast cancer in the Middle Eastern women. Germline mutations in TP-53, BARD1 and mismatch repair genes were more frequent than expected by chance. Conclusions: BRCA1/2 gene mutations are not a significant cause of heritable cancers in the Middle East. The region may benefit from a well-curated region-specific database accessible to clinicians and scientists where clinical and variants information can be deposited from all over the Middle East.

scholarly journals Family history of cancer and risk of pancreatic cancer: A pooled analysis from the Pancreatic Cancer Cohort Consortium (PanScan)

2010 ◽  
Vol 127 (6) ◽  
pp. 1421-1428 ◽  
Author(s):  
Eric J. Jacobs ◽  
Stephen J. Chanock ◽  
Charles S. Fuchs ◽  
Andrea LaCroix ◽  
Robert R. McWilliams ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Family History ◽  
Pooled Analysis ◽  
Family History Of Cancer ◽  
History Of ◽  
History Of Cancer

scholarly journals Family History of Cancer in Relation to Breast Cancer Subtypes in African American Women

2015 ◽  
Vol 25 (2) ◽  
pp. 366-373 ◽  
Author(s):  
Traci N. Bethea ◽  
Lynn Rosenberg ◽  
Nelsy Castro-Webb ◽  
Kathryn L. Lunetta ◽  
Lara E. Sucheston-Campbell ◽  
...  
Keyword(s):  
Breast Cancer ◽  
African American ◽  
Family History ◽  
African American Women ◽  
Breast Cancer Subtypes ◽  
American Women ◽  
Cancer Subtypes ◽  
Family History Of Cancer ◽  
History Of ◽  
History Of Cancer

scholarly journals Implications of ACMG guidelines to identify high-risk acute lymphoblastic leukemia patients with hereditary cancer susceptibility syndromes (HCSS) in a highly consanguineous population

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sara Aslam ◽  
Shabana ◽  
Mehboob Ahmed
Keyword(s):  
Genetic Testing ◽  
Family History ◽  
Cancer Susceptibility ◽  
Lymphoblastic Leukemia ◽  
Early Age ◽  
Pakistani Population ◽  
Parental Consanguinity ◽  
Family History Of Cancer ◽  
History Of ◽  
History Of Cancer

Abstract Background Hereditary cancer susceptibility syndrome (HCSS) contributes to the cancer predisposition at an early age, therefore, identification of HCSS has found to be crucial for surveillance, managing therapeutic interventions and refer the patients and their families for genetic counselling. The study aimed to identify ALL patients who meet the American College of Medical Genetics (ACMG) criteria and refer them for the genetic testing for HCSS as hereditary leukemia and hematologic malignancy syndrome, and to elucidate the significance of high consanguinity with the prevalence of inherited leukemia in Pakistani population. Methods A total of 300 acute lymphoblastic leukemia patients were recruited from the Children’s Hospital, Lahore, Pakistan from December 2018 to September 2019. A structured self-reporting questionnaire based on family and medical history of the disease was utilized for the data collection. Results In our cohort, 60.40% of ALL patients were identified to meet ACMG criteria. Among them, a large number of patients (40.65%) solely fulfil the criteria due to the presence of parental consanguinity. However, parental consanguinity showed protective impact on the onset at early age of disease [OD = 0.44 (0.25–0.77), p-value = 0.00] while, a family history of cancer increased the risk of cardiotoxicity [OD = 2.46 (1.15–5.24), p-value = 0.02]. Parental consanguinity shows no significant impact on the family history of cancer and the number of relatives with cancer. Conclusions More than 50% of the ALL patients were considered the strong candidates’ for genetic testing of HCSS in the Pakistani population, and parental consanguinity was the leading criteria fulfilled by the individuals when assessed through ACMG guidelines. Our study suggests revisiting ACMG guidelines, especially for the criterion of parental consanguinity, and formulating the score based criteria based on; genetic research, the toxicology profile, physical features, personal and family history of cancer for the identification of patients for the genetic testing.

scholarly journals Classification of variants of uncertain significance in BRCA1 and BRCA2 using personal and family history of cancer from individuals in a large hereditary cancer multigene panel testing cohort

2019 ◽  
Vol 22 (4) ◽  
pp. 701-708 ◽  
Author(s):  
Hongyan Li ◽  
Holly LaDuca ◽  
Tina Pesaran ◽  
Elizabeth C. Chao ◽  
Jill S. Dolinsky ◽  
...  
Keyword(s):  
Family History ◽  
In Silico ◽  
Functional Domains ◽  
Family History Of Cancer ◽  
Panel Testing ◽  
History Of ◽  
Multigene Panel Testing ◽  
History Of Cancer ◽  
Multigene Panel

Abstract Purpose Genetic testing of individuals often results in identification of genomic variants of unknown significance (VUS). Multiple lines of evidence are used to help determine the clinical significance of these variants. Methods We analyzed ~138,000 individuals tested by multigene panel testing (MGPT). We used logistic regression to predict carrier status based on personal and family history of cancer. This was applied to 4644 tested individuals carrying 2383 BRCA1/2 variants to calculate likelihood ratios informing pathogenicity for each. Heterogeneity tests were performed for specific classes of variants defined by in silico predictions. Results Twenty-two variants labeled as VUS had odds of >10:1 in favor of pathogenicity. The heterogeneity analysis found that among variants in functional domains that were predicted to be benign by in silico tools, a significantly higher proportion of variants were estimated to be pathogenic than previously indicated; that missense variants outside of functional domains should be considered benign; and that variants predicted to create de novo donor sites were also largely benign. Conclusion The evidence presented here supports the use of personal and family history from MGPT in the classification of VUS and will be integrated into ongoing efforts to provide large-scale multifactorial classification.

Sign in / Sign up

Export Citation Format

Share Document