Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Pancreatic Neoplasms: HELP
Articles by Kenneth Offit
Based on 8 articles published since 2010
(Why 8 articles?)
||||

Between 2010 and 2020, Kenneth Offit wrote the following 8 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review Counselling framework for moderate-penetrance cancer-susceptibility mutations. 2016

Tung, Nadine / Domchek, Susan M / Stadler, Zsofia / Nathanson, Katherine L / Couch, Fergus / Garber, Judy E / Offit, Kenneth / Robson, Mark E. ·Division of Hematology-Oncology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, Massachusetts 02215, USA. · Abramson Cancer Center, 3400 Spruce Street, Philadelphia, Pennsylvania 19104, USA, and the Department of Medicine, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Boulevard, Philadelphia, Pennsylvania 19104, USA. · Clinical Genetics Service, Memorial Sloan Kettering Cancer Center, 1275 York Avenue; and the Weill Cornell Medical College, 1300 York Avenue, New York, New York 10065, USA. · Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street South West, Rochester, Minnesota 55905, USA. · Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, Massachusetts 02215, USA. ·Nat Rev Clin Oncol · Pubmed #27296296.

ABSTRACT: The use of multigene panels for the assessment of cancer susceptibility is expanding rapidly in clinical practice, particularly in the USA, despite concerns regarding the uncertain clinical validity for some gene variants and the uncertain clinical utility of most multigene panels. So-called 'moderate-penetrance' gene mutations associated with cancer susceptibility are identified in approximately 2-5% of individuals referred for clinical testing; some of these mutations are potentially actionable. Nevertheless, the appropriate management of individuals harbouring such moderate-penetrance genetic variants is unclear. The cancer risks associated with mutations in moderate-penetrance genes are lower and different than those reported for high-penetrance gene mutations (such as mutations in BRCA1 and BRCA2, and those associated with Lynch syndrome). The extrapolation of guidelines for the management of individuals with high-penetrance variants of cancer-susceptibility genes to the clinical care of patients with moderate-penetrance gene mutations could result in substantial harm. Thus, we provide a framework for clinical decision-making pending the development of a sufficient evidence base to document the clinical utility of the interventions for individuals with inherited moderate-penetrance gene mutations associated with an increased risk of cancer.

2 Article Prospective Evaluation of Germline Alterations in Patients With Exocrine Pancreatic Neoplasms. 2018

Lowery, Maeve A / Wong, Winston / Jordan, Emmet J / Lee, Jonathan W / Kemel, Yelena / Vijai, Joseph / Mandelker, Diana / Zehir, Ahmet / Capanu, Marinela / Salo-Mullen, Erin / Arnold, Angela G / Yu, Kenneth H / Varghese, Anna M / Kelsen, David P / Brenner, Robin / Kaufmann, Erica / Ravichandran, Vignesh / Mukherjee, Semanti / Berger, Michael F / Hyman, David M / Klimstra, David S / Abou-Alfa, Ghassan K / Tjan, Catherine / Covington, Christina / Maynard, Hannah / Allen, Peter J / Askan, Gokce / Leach, Steven D / Iacobuzio-Donahue, Christine A / Robson, Mark E / Offit, Kenneth / Stadler, Zsofia K / O'Reilly, Eileen M. ·Department of Medicine. · David M. Rubenstein Center for Pancreatic Cancer Research. · Department of Medicine, Weill Cornell. · Robert and Kate Niehaus Center for Inherited Genomics. · Center for Molecular Oncology. · Department of Pathology. · Department of Epidemiology and Biostatistics. · Department of Surgery. ·J Natl Cancer Inst · Pubmed #29506128.

ABSTRACT: Background: Identification of pathogenic germline alterations (PGAs) has important clinical and therapeutic implications in pancreas cancer. We performed comprehensive germline testing (GT) in an unselected prospective cohort of patients with exocrine pancreatic neoplasms with genotype and phenotype association to facilitate identification of prognostic and/or predictive biomarkers and examine potential therapeutic implications. Methods: Six hundred fifteen unselected patients with exocrine pancreatic neoplasms were prospectively consented for somatic tumor and matched sample profiling for 410-468 genes. GT for PGAs in 76 genes associated with cancer susceptibility was performed in an "identified" manner in 356 (57.9%) patients and in an "anonymized" manner in 259 (42.1%) patients, using an institutional review board-approved protocol. Detailed clinical and pathological features, response to platinum, and overall survival (OS) were collected for the identified cohort. OS was analyzed with Kaplan-Meier curves. Results: PGAs were present in 122 (19.8%) of 615 patients involving 24 different genes, including BRCA1/2, ATM, PALB2, and multiple additional genes associated with the DNA damage response pathway. Of 122 patients with germline alterations, 41.8% did not meet current guidelines for GT. The difference in median OS was not statistically significant between patients with and without PGA (50.8 months, 95% confidence interval = 34.5 to not reached, two-sided P = .94). Loss of heterozygosity was found in 60.0% of BRCA1/2. Conclusions: PGAs frequently occur in pancreas exocrine neoplasms and involve multiple genes beyond those previously associated with hereditary pancreatic cancer. These PGAs are therapeutically actionable in about 5% to 10% of patients. These data support routinely offering GT in all pancreatic ductal adenocarcimona patients with a broad panel of known hereditary cancer predisposition genes.

3 Article Genetic/Familial High-Risk Assessment: Breast and Ovarian, Version 2.2015. 2016

Daly, Mary B / Pilarski, Robert / Axilbund, Jennifer E / Berry, Michael / Buys, Saundra S / Crawford, Beth / Farmer, Meagan / Friedman, Susan / Garber, Judy E / Khan, Seema / Klein, Catherine / Kohlmann, Wendy / Kurian, Allison / Litton, Jennifer K / Madlensky, Lisa / Marcom, P Kelly / Merajver, Sofia D / Offit, Kenneth / Pal, Tuya / Rana, Huma / Reiser, Gwen / Robson, Mark E / Shannon, Kristen Mahoney / Swisher, Elizabeth / Voian, Nicoleta C / Weitzel, Jeffrey N / Whelan, Alison / Wick, Myra J / Wiesner, Georgia L / Dwyer, Mary / Kumar, Rashmi / Darlow, Susan. ·Fox Chase Cancer Center · The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute · The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins · St. Jude Children’s Research Hospital/The University of Tennessee Health Science Center · Huntsman Cancer Institute at the University of Utah · UCSF Helen Diller Family Comprehensive Cancer Center · University of Alabama at Birmingham Comprehensive Cancer Center · FORCE-Facing Our Risk of Cancer Empowered · Dana-Farber/Brigham and Women’s Cancer Center · Robert H. Lurie Comprehensive Cancer Center of Northwestern University · University of Colorado Cancer Center · Stanford Cancer Institute · The University of Texas MD Anderson Cancer Center · UC San Diego Moores Cancer Center · Duke Cancer Institute · University of Michigan Comprehensive Cancer Center · Memorial Sloan Kettering Cancer Center · Moffitt Cancer Center · Fred & Pamela Buffett Cancer Center · Massachusetts General Hospital Cancer Center · University of Washington Medical Center/Seattle Cancer Care Alliance · Roswell Park Cancer Institute · City of Hope Comprehensive Cancer Center · Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine · Mayo Clinic Cancer Center · Vanderbilt-Ingram Cancer Center · National Comprehensive Cancer Network ·J Natl Compr Canc Netw · Pubmed #26850485.

ABSTRACT: The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast and Ovarian provide recommendations for genetic testing and counseling and risk assessment and management for hereditary cancer syndromes. Guidelines focus on syndromes associated with an increased risk of breast and/or ovarian cancer and are intended to assist with clinical and shared decision-making. These NCCN Guidelines Insights summarize major discussion points of the 2015 NCCN Genetic/Familial High-Risk Assessment: Breast and Ovarian panel meeting. Major discussion topics this year included multigene testing, risk management recommendations for less common genetic mutations, and salpingectomy for ovarian cancer risk reduction. The panel also discussed revisions to genetic testing criteria that take into account ovarian cancer histology and personal history of pancreatic cancer.

4 Article Identification of germline genetic mutations in patients with pancreatic cancer. 2015

Salo-Mullen, Erin E / O'Reilly, Eileen M / Kelsen, David P / Ashraf, Asad M / Lowery, Maeve A / Yu, Kenneth H / Reidy, Diane L / Epstein, Andrew S / Lincoln, Anne / Saldia, Amethyst / Jacobs, Lauren M / Rau-Murthy, Rohini / Zhang, Liying / Kurtz, Robert C / Saltz, Leonard / Offit, Kenneth / Robson, Mark E / Stadler, Zsofia K. ·Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, New York. · Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York. ·Cancer · Pubmed #26440929.

ABSTRACT: BACKGROUND: Pancreatic adenocarcinoma (PAC) is part of several cancer predisposition syndromes; however, indications for genetic counseling/testing are not well-defined. In the current study, the authors sought to determine mutation prevalence and characteristics that are predictive of an inherited predisposition for PAC. METHODS: A total of 175 consecutive patients with PAC who underwent clinical genetics assessment at Memorial Sloan Kettering Cancer Center between 2011 and 2014 were identified. Clinical data, family history, and germline results were evaluated. RESULTS: Among 159 patients with PAC who pursued genetic testing, 24 pathogenic mutations were identified (15.1%; 95% confidence interval, 9.5%-20.7%), including BRCA2 (13 mutations), BRCA1 (4 mutations), p16 (2 mutations), PALB2 (1 mutation), and Lynch syndrome (4 mutations). BRCA1/BRCA2 prevalence was 13.7% in Ashkenazi Jewish (AJ) patients (95 patients) and 7.1% in non-AJ patients (56 patients). In AJ patients with a strong, weak, or absent family history of BRCA-associated cancers, the mutation prevalence was 16.7%, 15.8%, and 7.4%, respectively. The mean age at the time of diagnosis in all mutation carriers was 58.5 years (range, 45-75 years) compared with 64 years (range, 27-87 years) in those not carrying a mutation (P = .02). Although BRCA2 was the most common mutation identified, no patients with early-onset PAC (diagnosed at age ≤ 50 years) harbored a BRCA2 mutation and the mean age at diagnosis in BRCA2 carriers was equivalent to that of individuals who were not mutation carriers (P = .34). Mutation prevalence in patients with early-onset disease (21 patients) was 28.6%, including BRCA1 (2 mutations), p16 (2 mutations), MSH2 (1 mutation), and MLH1 (1 mutation). CONCLUSIONS: Mutations in BRCA2 account for > 50% of patients with PAC with an identified susceptibility syndrome. AJ patients were found to have high BRCA1/BRCA2 prevalence regardless of personal/family history, suggesting that ancestry alone indicates a need for genetic evaluation. With the exception of BRCA2-associated PAC, an inherited predisposition for PAC is associated with an earlier age at PAC diagnosis, suggesting that this subset of patients may also represent a population warranting further evaluation.

5 Article Genome-wide analysis of the role of copy-number variation in pancreatic cancer risk. 2014

Willis, Jason A / Mukherjee, Semanti / Orlow, Irene / Viale, Agnes / Offit, Kenneth / Kurtz, Robert C / Olson, Sara H / Klein, Robert J. ·Department of Medicine, Memorial Sloan-Kettering Cancer Center New York, NY, USA ; Program in Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center New York, NY, USA. · Program in Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center New York, NY, USA. · Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center New York, NY, USA. · Genomics Core Laboratory, Memorial Sloan-Kettering Cancer Center New York, NY, USA. · Department of Medicine, Memorial Sloan-Kettering Cancer Center New York, NY, USA. ·Front Genet · Pubmed #24592275.

ABSTRACT: Although family history is a risk factor for pancreatic adenocarcinoma, much of the genetic etiology of this disease remains unknown. While genome-wide association studies have identified some common single nucleotide polymorphisms (SNPs) associated with pancreatic cancer risk, these SNPs do not explain all the heritability of this disease. We hypothesized that copy number variation (CNVs) in the genome may play a role in genetic predisposition to pancreatic adenocarcinoma. Here, we report a genome-wide analysis of CNVs in a small hospital-based, European ancestry cohort of pancreatic cancer cases and controls. Germline CNV discovery was performed using the Illumina Human CNV370 platform in 223 pancreatic cancer cases (both sporadic and familial) and 169 controls. Following stringent quality control, we asked if global CNV burden was a risk factor for pancreatic cancer. Finally, we performed in silico CNV genotyping and association testing to discover novel CNV risk loci. When we examined the global CNV burden, we found no strong evidence that CNV burden plays a role in pancreatic cancer risk either overall or specifically in individuals with a family history of the disease. Similarly, we saw no significant evidence that any particular CNV is associated with pancreatic cancer risk. Taken together, these data suggest that CNVs do not contribute substantially to the genetic etiology of pancreatic cancer, though the results are tempered by small sample size and large experimental variability inherent in array-based CNV studies.

6 Article Prevalence of BRCA1 and BRCA2 mutations in Ashkenazi Jewish families with breast and pancreatic cancer. 2012

Stadler, Zsofia K / Salo-Mullen, Erin / Patil, Sujata M / Pietanza, M Catherine / Vijai, Joseph / Saloustros, Emmanouil / Hansen, Nichole A L / Kauff, Noah D / Kurtz, Robert C / Kelsen, David P / Offit, Kenneth / Robson, Mark E. ·Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. ·Cancer · Pubmed #21598239.

ABSTRACT: BACKGROUND: Germline mutations in the BRCA2 cancer susceptibility gene are associated with an increased risk of pancreatic cancer (PC). Breast-pancreas cancer families with BRCA1 mutations have also been observed. The influence of a family history (FH) of PC on BRCA mutation prevalence in patients with breast cancer (BC) is unknown. METHODS: A clinical database review (2000-2009) identified 211 Ashkenazi Jewish (AJ) BC probands who 1) underwent BRCA1/2 mutation analysis by full gene sequencing or directed testing for Ashkenazi founder mutations (BRCA1: 185delAG and 5382insC; BRCA2: 6174delT) and 2) had a FH of PC in a first-, second-, or third-degree relative. For each proband, the pretest probability of identifying a BRCA1/2 mutation was estimated using the Myriad II model. The observed-to-expected (O:E) mutation prevalence was calculated for the entire group. RESULTS: Of the 211 AJ BC probands with a FH of PC, 30 (14.2%) harbored a BRCA mutation. Fourteen (47%) of the mutations were in BRCA1 and 16 (53%) were in BRCA2. Patients diagnosed with BC at age ≤ 50 years were found to have a higher BRCA1/2 mutation prevalence than probands with BC who were diagnosed at age > 50 years (21.1% vs 6.9%; P = .003). In patients with a first-, second-, or third-degree relative with PC, mutation prevalences were 15.4%, 15.3%, and 8.6%, respectively (P = .58). In the overall group, the observed BRCA1/2 mutation prevalence was 14.2% versus an expected prevalence of 11.8% (O:E ratio, 1.21; P = .15). CONCLUSIONS: BRCA1 and BRCA2 mutations are observed with nearly equal distribution in AJ breast-pancreas cancer families, suggesting that both genes are associated with PC risk. In this population, a FH of PC was found to have a limited effect on mutation prevalence.

7 Article Including additional controls from public databases improves the power of a genome-wide association study. 2011

Mukherjee, Semanti / Simon, Jennifer / Bayuga, Sharon / Ludwig, Emmy / Yoo, Sarah / Orlow, Irene / Viale, Agnes / Offit, Kenneth / Kurtz, Robert C / Olson, Sara H / Klein, Robert J. ·Gerstner Sloan-Kettering Graduate School of Biomedical Sciences, Memorial Sloan-Kettering Cancer Center, New York, USA. ·Hum Hered · Pubmed #21849791.

ABSTRACT: Though genome-wide association studies (GWAS) have identified numerous susceptibility loci for common diseases, their use is limited due to the expense of genotyping large cohorts of individuals. One potential solution is to use 'additional controls', or genotype data from control individuals deposited in public repositories. While this approach has been used by several groups, the genetically heterogeneous nature of the population of the United States makes this approach potentially problematic. We empirically investigated the utility of this approach in a US-based GWAS. In a small GWAS of pancreatic cancer in New York, we observed clear population structure differences relative to controls from the database of Genotypes and Phenotypes (dbGaP). When we conduct the GWAS using these additional controls, we find large inflation of the test statistic that is properly corrected by using eigenvectors from principal components analysis as covariates. To deal with errors introduced due to different sources, we propose simultaneously genotyping a small number of controls along with cases and then comparing this group to the additional controls. We show that removing SNPs that show differences between these control groups reduces false-positive findings. Thus, through an empirical approach, this report provides practical guidance for using additional controls from publicly available datasets.

8 Article Germline PALB2 mutation analysis in breast-pancreas cancer families. 2011

Stadler, Zsofia K / Salo-Mullen, Erin / Sabbaghian, Nelly / Simon, Jennifer A / Zhang, Liying / Olson, Sara H / Kurtz, Robert / Offit, Kenneth / Foulkes, William D / Robson, Mark E / Tischkowitz, Marc. ·Clinical Genetics and Gastroenterology Services, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. stadlerz@mskcc.org ·J Med Genet · Pubmed #21415078.

ABSTRACT: BACKGROUND: Germline mutations in the PALB2 gene have been implicated in both breast cancer and pancreatic cancer susceptibility. The extent to which PALB2 mutations account for cancer susceptibility in breast-pancreas cancer families is unknown. METHODS: High Resolution Melting analysis and Multiplex Ligation-dependent Probe Amplification were performed to investigate the prevalence of PALB2 mutations in patients with either a personal history of both breast and pancreatic cancer or a personal history of breast cancer and a family history of a first degree relative with pancreatic cancer. RESULTS: No PALB2 mutations were identified in 77 breast-pancreas cancer families, which included 22 probands with a personal history of both breast and pancreatic cancer. CONCLUSION: Mutations within the PALB2 gene are rare events that do not account for a substantial proportion of cancer susceptibility in breast-pancreas cancer families. Routine screening of breast-pancreas cancer families for the presence of PALB2 mutations appears to be low yield.