scholarly journals Implementation of Multigene Germline and Parallel Somatic Genetic Testing in Epithelial Ovarian Cancer: SIGNPOST Study

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4344
Author(s):  
Dhivya Chandrasekaran ◽  
Monika Sobocan ◽  
Oleg Blyuss ◽  
Rowan E. Miller ◽  
Olivia Evans ◽  
...  
Keyword(s):  
Nurse Specialist ◽  
Panel Testing ◽  
Testing Strategies ◽  
Resection Status ◽  
Significant Difference ◽  
Surgery Timing ◽  
Testing Approach ◽  
Brca1 Brca2 ◽  
Surgical Oncologist ◽  
Variant Identification

We present findings of a cancer multidisciplinary-team (MDT) coordinated mainstreaming pathway of unselected 5-panel germline BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 and parallel somatic BRCA1/BRCA2 testing in all women with epithelial-OC and highlight the discordance between germline and somatic testing strategies across two cancer centres. Patients were counselled and consented by a cancer MDT member. The uptake of parallel multi-gene germline and somatic testing was 97.7%. Counselling by clinical-nurse-specialist more frequently needed >1 consultation (53.6% (30/56)) compared to a medical (15.0% (21/137)) or surgical oncologist (15.3% (17/110)) (p < 0.001). The median age was 54 (IQR = 51–62) years in germline pathogenic-variant (PV) versus 61 (IQR = 51–71) in BRCA wild-type (p = 0.001). There was no significant difference in distribution of PVs by ethnicity, stage, surgery timing or resection status. A total of 15.5% germline and 7.8% somatic BRCA1/BRCA2 PVs were identified. A total of 2.3% patients had RAD51C/RAD51D/BRIP1 PVs. A total of 11% germline PVs were large-genomic-rearrangements and missed by somatic testing. A total of 20% germline PVs are missed by somatic first BRCA-testing approach and 55.6% germline PVs missed by family history ascertainment. The somatic testing failure rate is higher (23%) for patients undergoing diagnostic biopsies. Our findings favour a prospective parallel somatic and germline panel testing approach as a clinically efficient strategy to maximise variant identification. UK Genomics test-directory criteria should be expanded to include a panel of OC genes.

35 Wound Improvement Project: Improving Skill Sustainment and Confidence

2020 ◽  
Vol 41 (Supplement_1) ◽  
pp. S24-S25
Author(s):  
Sarah K Shingleton ◽  
Alexandra J Helms ◽  
Leopoldo C Cancio ◽  
Monica L Abbott ◽  
Corey A Miner
Keyword(s):  
Wound Care ◽  
Care Quality ◽  
Nurse Specialist ◽  
Positive Trend ◽  
Evaluation Tool ◽  
Improvement Project ◽  
Self Evaluation ◽  
Burn Center ◽  
Significant Difference ◽  
Student’S T

Abstract Introduction New burn intensive care unit (BICU) nurses in the Burn Center complete an evidence-based preceptorship to include standardized wound care education that is reinforced throughout preceptorship. A gap in skill sustainment was identified; factors include lack of a formal sustainment program, inconsistent reinforcement of wound care skills and a perceived decrease in pride in wound care. The purposes of this project are to 1) develop and implement a wound care skill sustainment program 2) re-establish confidence in wound care and 3) improve the quality of wound care delivered in the BICU. Methods A Wound Improvement Project (WIP) committee was formed FEB 2018 consisting 8 BICU nurses; the BICU Nurse Manager and Wound Clinical Nurse Specialist serve as consultants. WIP developed several learning modules and is now developing a wound skill sustainment program and evaluation tool based on the Burn Nurse Competency Initiative (BNCI) standards. BICU staff complete an anonymous survey about wound care confidence every 6 months. WIP mentors and evaluates competency through direct observation during 3 assigned shifts with each BICU nurse. Wound care documentation is audited monthly and a wound care quality audit tool is being developed. Descriptive statistics, student’s T-test, and ANOVA were used. Results The confidence survey was given in Spring 2018 (n=52), Winter 2019 (n=33) and Summer 2019 (n=64); each question showed significant improvement. Notably “how confident would you be doing a full body wound care by yourself with some help turning” improved from 4.12 (±1.17) to 4.64 (±0.65, p=.01). 24 BICU staff have been evaluated with 40 pending completion. No significant difference was found in skill competency between the 3 WIP assigned shifts; however self-evaluation for “how comfortable/confident do you feel advocating for a different type of wound care treatment for your patient” improved from 6.1 (±2.2) to 7.5 (±1.9, p&lt; .0001). Average wound documentation scores improved from 85% in FEB 2018 to 99% in FEB 2019. Conclusions Wound care confidence and documentation have improved since initiation of WIP. Targeted education, bedside tools and workshops have all contributed. There is a positive trend (not significant) towards improved skill competency this is likely due to tool modifications and the small number of staff evaluated to date. Staff feedback has been positive with most staff finding WIP helpful. The long-term goal is to expand WIP to all areas of the Burn Center. Applicability of Research to Practice BNCI standards are a framework for skill sustainment and progression of staff from competent towards proficient and expert. Development and evaluation of nurse-led sustainment programs are needed across the burn community.

scholarly journals Surgery Delay Increases Length of Stay in Thoracolumbar Trauma

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Lawrence Zeldin ◽  
Sean N Neifert ◽  
Robert J Rothrock ◽  
Ian T McNeill ◽  
Jonathan S Gal ◽  
...  
Keyword(s):  
Length Of Stay ◽  
Spinal Injury ◽  
Specific Effect ◽  
Spinal Trauma ◽  
Spine Injury ◽  
Complication Rates ◽  
Improvement Program ◽  
Delayed Surgery ◽  
Significant Difference ◽  
Surgery Timing

Abstract INTRODUCTION The ideal timing from admission of a thoracolumbar spinal trauma patient to the start of surgery at US trauma centers remains a hotly contested area of debate. The effect of surgical latency on patient outcomes in thoracolumbar trauma remains unclear. METHODS All 2013 to 2015 thoracolumbar spinal trauma cases from the American College of Surgeons Trauma Quality Improvement Program (TQIP) were analyzed. Patients with unsurvivable spine injury, polytraumas (serious injuries in more than one bodily region), and those discharged within 24 h were excluded. Patients were classified into 3 groups by surgery timing: less than 8 h (early, N = 1699), between 8 and 24 h (normal, N = 946), and over 24 h (delayed, N = 1601). Mortality, length of stay (LOS), and complication rates were compared between groups. Demographic variables and complication rates were compared. Multivariate logistic regression was utilized to determine the specific effect of surgery timing on outcomes. RESULTS Patients with earlier surgery presented with more severe spinal trauma (P < .0001). Patients in the normal surgical timing cohort were most likely to have altered mental status (4.97% vs 3.24%, P = .05), and less likely to suffer from UTI (4.97% vs 3.24%, P = .03). Patients in the delayed cohort were older (46.2 vs 43.7 yr, P = .0003), more likely to have a longer LOS (11.3 vs 10.6 d, P = .02), return to the ICU (2.94% vs 1.29%, P = .001), experience unplanned intubation (2.06% vs 1%, P = .01) and suffer from cardiac arrest (0.53% vs 1.19%, P = .04). Upon multivariate analysis, delayed surgery was an independent risk factor for prolonged LOS (OR: 1.21, 95% CI: 0.56-1.87, P = .0003). CONCLUSION Patients with earlier surgery possessed more severe spinal injury. When adjusting for demographics and severity, no significant difference is seen in mortality between the different surgery times; however, LOS is prolonged in patients with delayed surgery.

Performance of mutation risk prediction models in a racially diverse multi-gene panel testing cohort.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1523-1523
Author(s):  
Gregory Idos ◽  
Katherine G Roth ◽  
Leah Naghi ◽  
Charite Nicolette Ricker ◽  
Julie Culver ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Genetic Testing ◽  
Prediction Models ◽  
Brca2 Mutation ◽  
Pathogenic Mutation ◽  
Gene Panel ◽  
Panel Testing ◽  
Gene Panel Testing ◽  
Brca1 Brca2 ◽  
Racial Ethnic

1523 Background: Mutation carrier prediction models are clinically useful tools for identifying candidates for genetic counseling and testing. Consensus guidelines recommend germline genetic testing for those with a carrier probability (CP) of approximately 5% or higher. However, prediction models may perform less well among racial/ethnic minorities. Our hypothesis is that pathogenic mutations (PM) are identifiable in a clinically meaningful fraction of racially/ethnically diverse patients with a CP of < 5%. Methods: We conducted a multicenter prospective clinical trial of patients undergoing cancer-risk assessment using a 25 gene panel, which include 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 recruited from August 2014 to November 2016 at three centers. Patients were enrolled if they met standard clinical criteria for genetic testing or were predicted to have a ≥2.5% probability of inherited cancer susceptibility using validated prediction models. We evaluated the CP of patients with a PM in BRCA1, BRCA2, and/or a mismatch repair (MMR) gene using the following models: (1) BRCApro, (2) MMRpro and (3) PREMM1,2,6. Results: Of 2000 patients enrolled in this cohort, 80.6% are female (n = 1612). Regarding race/ethnicity, the cohort is 40.1% Non-Hispanic White (n = 802), 37.4% Hispanic (n = 748), 11.5% Asian (n = 230), 3.9% Black (n = 78), and 7.1% Other (n = 142). Among 241 (12.1%) patients who tested positive for a pathogenic mutation, 76 (31.5%) patients had a BRCA1 or BRCA2 mutation. Of those, 52 (68.4%) patients had a BRCApro CP of < 5%. Thirty-eight (15.8%) patients had a pathogenic mutation in an MMR gene: 19 (50.0%) had an MMRpro CP of < 5%, while 13 (34.2%) had a PREMM1,2,6 CP of < 5%. The racial/ethnic distribution of BRCA1/2 or MMR mutation carriers is similar to that of the whole cohort. Conclusions: In a diverse cohort of patients undergoing 25-gene multiple-gene panel testing, half or more carriers of BRCA1/2 or MMR mutations had a CP of < 5%, the consensus guideline-recommended cutoff for genetic testing. These results support a lower threshold for genetic testing guidelines. Clinical trial information: NCT02324062.

scholarly journals Cancer and Fertility Program Improves Patient Satisfaction With Information Received

2016 ◽  
Vol 34 (15) ◽  
pp. 1780-1786 ◽  
Author(s):  
Joanne F. Kelvin ◽  
Bridgette Thom ◽  
Catherine Benedict ◽  
Jeanne Carter ◽  
Stacie Corcoran ◽  
...  
Keyword(s):  
Decision Making ◽  
Patient Satisfaction ◽  
Clinical Nurse Specialist ◽  
Cancer Center ◽  
Nurse Specialist ◽  
Cross Sectional ◽  
Clinical Nurse ◽  
Specialist Consultation ◽  
Significant Difference ◽  
Cancer And Fertility

Purpose A cancer and fertility program was established at a large cancer center to support clinicians in discussing treatment-related fertility risks and fertility preservation (FP) options with patients and in referring patients to reproductive specialists. The program provides resources, clinician education, and fertility clinical nurse specialist consultation. This study evaluated the program’s impact on patient satisfaction with information received. Patients and Methods Retrospective cross-sectional surveys assessed satisfaction before (cohort 1 [C1]) and after (cohort 2 [C2]) program initiation. Questionnaires were investigator-designed, gender-specific, and anonymous. Results Most C1 (150 males, 271 females) and C2 (120 males, 320 females) respondents were 2 years postdiagnosis; the most frequently reported cancers were testicular, breast, and lymphoma. A significant difference in satisfaction with the amount of information received was seen between C1 and C2. For males, satisfaction with information on fertility risks was high in both cohorts but significantly greater in C2 for information on sperm banking (χ2 = 9.3, P = .01) and finding a sperm bank (χ2 = 13.3, P = .001). For females, satisfaction with information was significantly greater in C2 for information on fertility risks (χ2 = 62.1, P < .001), FP options (χ2 = 71.9, P < .001), help with decision making (χ2 = 80.2, P < .001), and finding a reproductive endocrinologist (χ2 = 60.5, P < .001). Among patients who received and read information materials, 96% of males and 99% of females found them helpful. Among C2 females, fertility clinical nurse specialist consultation was associated with significantly greater satisfaction with information on FP options (χ2 = 11.2, P = .004), help with decision making (χ2 = 10.4, P = .006), and finding a reproductive endocrinologist (χ2 = 22.6, P < .001), with 10% reporting lack of knowledge as a reason for not pursuing FP. Conclusion Improvements in patient satisfaction with information received demonstrate the potential for fertility programs in cancer care settings to improve the quality of clinician-patient discussions about fertility.

scholarly journals REHABILITATION NURSING: DIFFERENTIATION IN PROMOTING THE AUTONOMY OF THE ELDERLY

2021 ◽  
Vol 4 (1) ◽  
pp. 15-22
Author(s):  
Andreia Maria Lima ◽  
Maria Manuela Ferreira da Silva Martins ◽  
Maria Salomé Martins Ferreira ◽  
Francisco Sampaio ◽  
Soraia Dornelles Schoeller ◽  
...  
Keyword(s):  
Activities Of Daily Living ◽  
Daily Living ◽  
The Elderly ◽  
Nurse Specialist ◽  
Snowball Sampling ◽  
Cross Sectional ◽  
Rehabilitation Programs ◽  
Instrumental Activities ◽  
Significant Difference ◽  
Specialist Nurses

Introduction: The promotion of autonomy, through the use of nursing interventions that promote physical, cognitive and social integration skills, are added competencies of nurses specialized in rehabilitation nursing, so it is important to realize whether these professionals invest in this area in their practices. Objectives: To identify and compare the perception of nurses who are specialists in rehabilitation nursing and nurses who are specialists in other specialty areas. Methodology: A descriptive, correlational, cross-sectional, quantitative study with non-probabilistic snowball sampling. For data collection, the Self-Assessment Scale of Elderly Autonomy was used between September and October 2020. Results: The sample consists of 151 specialist nurses, 72 specialists in rehabilitation nursing, and 79 specialists in other specialty areas. All specialist nurses promote the autonomy of the elderly with less visibility in the development of interventions for instrumental activities of daily living. It is perceived that the nurse specialist in rehabilitation nursing promotes more autonomy of the elderly on a broader scale (p <0.05), with a more significant difference concerning the development of physical and cognitive interventions (<0.001). Conclusion: All specialist nurses perceive that they promote the elderly's autonomy but have weaknesses in interventions that promote instrumental activities of daily living. The specialist nurses in rehabilitation nursing realize that they promote more autonomy for the elderly, probably due to the implementation of rehabilitation programs aimed at this promotion.

scholarly journals Prevalence of Germline Pathogenic and Likely Pathogenic Variants in Patients With Second Breast Cancers

2020 ◽  
Vol 4 (6) ◽  
Author(s):  
Katharine A Yao K ◽  
Jacob Clifford ◽  
Shuwei Li ◽  
Holly LaDuca ◽  
Peter Hulick ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Race And Ethnicity ◽  
Statistical Tests ◽  
Diagnostic Testing ◽  
Breast Cancers ◽  
Breast Cancer Predisposition ◽  
Panel Testing ◽  
Pathogenic Variants ◽  
Predisposition Genes ◽  
Brca1 Brca2

Abstract Background Few studies have examined gene-specific associations with contralateral and/or second breast cancer (SBC). Methods The frequency of pathogenic and likely pathogenic (P/LP) variants in clinically actionable genes (BRCA1, BRCA2, PTEN, TP53, CHEK2, CDH1, ATM, PALB2, NBN, and NF1) was compared between women with a primary breast cancer (PBC) and SBC who underwent multigene panel testing at a single diagnostic testing laboratory. Race- and ethnicity-specific logistic regression burden tests adjusted for age at diagnosis of first breast cancer, histology, presence of first- or second-degree relatives with breast cancer, and prior testing for BRCA1/2 genes were used to test for associations with SBC. All statistical tests were 2-sided. Results The study was comprised of 75 550 women with PBC and 7728 with SBC. Median time between breast cancers for SBC was 11 (interquartile range = 6–17) years. Restricting to women tested for all actionable genes (n = 60 310), there were 4231 (7.8%) carriers of P/LP variants in actionable genes among the controls (PBC) compared with 652 (11.1%) women with SBC (P&lt; .001). Among Caucasians, exclusive of Ashkenazi Jewish women, those carrying a P/LP variant in a clinically actionable gene were 1.44 (95% confidence interval [CI] = 1.30 to 1.60) times as likely to have SBC than noncarriers, after accounting for potential confounders. Among African American and Hispanic women, a P/LP variant in a clinically actionable gene was 1.88 (95% CI = 1.36 to 2.56) and 1.66 (9% CI = 1.02 to 2.58) times as likely to be associated with SBC, respectively (P &lt; .001 and P = .03). Conclusion Women with P/LP variants in breast cancer predisposition genes are more likely to have SBC than noncarriers. Prospective studies are needed confirm these findings.

scholarly journals Platinum response characteristics of patients with pancreatic ductal adenocarcinoma and a germline BRCA1, BRCA2 or PALB2 mutation

2019 ◽  
Vol 122 (3) ◽  
pp. 333-339 ◽  
Author(s):  
Max M. Wattenberg ◽  
Daniella Asch ◽  
Shun Yu ◽  
Peter J. O’Dwyer ◽  
Susan M. Domchek ◽  
...  
Keyword(s):  
Objective Response ◽  
Clinical Trial Design ◽  
Progression Free Survival ◽  
Ductal Adenocarcinoma ◽  
Control Group ◽  
Response Characteristics ◽  
Platinum Based Chemotherapy ◽  
Significant Difference ◽  
Palb2 Mutation ◽  
Brca1 Brca2

Abstract Background Retrospective studies suggest a survival benefit when platinum-based chemotherapy is administered to patients with pancreatic cancer harbouring a germline mutation in BRCA1, BRCA2 or PALB2 (mut-positive PDAC). However, the objective response rate (ORR) and real-world progression free survival (rwPFS) achieved with such treatment remain ill-defined. Methods Twenty-six patients with advanced-stage mut-positive PDAC who had been treated with platinum-based therapy were matched by age, race and sex to 52 platinum-treated control PDAC patients. Responses to therapy were determined by RECIST v1.1, performed by blinded radiology review. Measured outcomes included ORR and rwPFS. Results The ORR in mut-positive patients was 58% compared to 21% in the control group (p = 0.0022). There was no significant difference in ORR between platinum regimens in mut-positive patients (p = 0.814), whereas in control patients, the only observed responses were to FOLFIRINOX. rwPFS was 10.1 mo. for mut-positive patients and 6.9 mo. for controls (HR 0.43; 95% CI 0.25–0.74; 0.0068). Conclusion Mut-positive PDAC has a high ORR and prolonged rwPFS to platinum-based chemotherapy. These findings may have implications particularly in the neoadjuvant setting, and for future clinical trial design, and highlight the importance of early germline testing in patients with PDAC.

Landscape of multilocus inherited neoplasia alleles syndrome in China.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13027-e13027
Author(s):  
Quchang Ouyang ◽  
Jie Gao ◽  
Jun Huang ◽  
Pingping Dai ◽  
Mingming Zhang ◽  
...  
Keyword(s):  
Molecular Subtype ◽  
Dna Mismatch ◽  
Msh6 Mutation ◽  
Panel Testing ◽  
Damage Repair ◽  
Dna Mismatch Repair Genes ◽  
Study Results ◽  
Brca1 Brca2 ◽  
Gene Panels ◽  
Repair Genes

e13027 Background: Comprehensive gene panels are able to identify patients with more than one pathogenic germline mutations. This phenomenon is known as multilocus inherited neoplasia alleles syndrome (MINAS). The frequency and phenotype of double heterozygous carriers in China are still unknown. Methods: A cohort of 12514 unrelated patients with solid tumor were screened using a validated panel. DNA damage repair-associated genes ( BRCA1, BRCA2, PALB2, ATM) and DNA mismatch repair genes ( MLH1, MSH2, MSH6, PMS2, MLH3, MSH3, PMS1) are taken focused on this study. Results: 10 (2.16%) cases harboring two pathogenic/likely pathogenic mutations were identified in 464 patients with germline variant. All patients had at least one high-risk gene mutation except for G10(LC, 73y), which carried 2 ATM variants in the same allele. All patients developed tumors associated with only one of the mutation identified until now. Among 3 patients had PMS2/MSH6 mutation, G6 & G7 did not translated into recognized Lynch Syndrome due to abnormal BRCA1/2(H-risk for BC), while G8 harboring ATM (M-risk for BC) mutation developed to CRC. All of the five patients developed to breast cancer were TNBC molecular subtype. The median ages of diagnosis for BC were similar to single variation patients (44.3 vs 42, p=0.6190). Conclusions: Two double heterozygotes did not appear to have severe or different manifestations than single heterozygote. With the growing implementation of NGS based panel testing, relevant variants in two (or more) genes will be found more frequently. [Table: see text]

Prevalence and spectrum of pathogenic variants among patients with multiple primary cancers.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10595-10595
Author(s):  
Brittany L. Bychkovsky ◽  
Min-Tzu Lo ◽  
Yuan Tian ◽  
Amal Yussuf ◽  
Carrie Horton ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Cancer Diagnosis ◽  
Age At Diagnosis ◽  
Multiple Primary Cancers ◽  
Cancer Type ◽  
Exact Test ◽  
Panel Testing ◽  
Pathogenic Variants ◽  
Multiple Primary ◽  
Brca1 Brca2

10595 Background: Multiple primary cancers (MPCs) are a hallmark of cancer predisposition syndromes. We aim to characterize the frequency of germline pathogenic/likely pathogenic variants (PVs) among patients with MPCs. Herein we report the frequency of PVs by sex, number of cancers and age at diagnosis among a laboratory-based cohort of patients with MPCs. Methods: Patients with MPCs who underwent germline genetic testing with Ambry Genetics from 3/2012 to 12/2016 were included in our cohort. Eligible individuals had multigene panel testing, which included 21 genes, at minimum: ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, MUTYH, NBN, NF1, PALB2, PMS2, PTEN, RAD51C, RAD51D, STK11, and TP53. Clinical factors including age at diagnosis, age at testing and cancer type were obtained from test requisition forms and clinical notes. Patients with > 1 PVs were excluded from the analysis. Using Rv.3.3.3., the frequencies of PVs by sex, number of cancers and age at diagnosis were compared using two-sided χ2 tests or Fisher’s exact test when the number was < 10. Results: Of the 9820 patients with MPCs tested for the 21 genes above, 104 (1.1%) had multiple PVs and were excluded. Among the remaining 9716 patients in the analytic cohort, most were female (91.1%) and white (71.0%). The median age at testing was 63 years (IQR: 16) and the median ages of first and second cancer diagnosis were 49 (IQR: 18) and 58 (IQR: 17) years, respectively. Overall, 1406 (14.5%) were found to have PVs: 14.3% of females and 16.2% of males. The prevalence of PVs increased with the number of primary cancers (PCs) as follows, 2 PCs: 13.1% (95% CI:12.4-13.8%), 3 PCs: 15.9% (95% CI:14.0-18.0%), >4 PCs: 18.0% (95% CI:13.7-23.3%), (p < 0.01). Among patients with 2 PCs (n = 8145), differences in the prevalence of PVs by age at diagnosis were significant: 2 PCs diagnosed at an age < 50 (13.5%, 95% CI:12.0-15.1%), 1 PC diagnosed at an age < 50 (14.8%, 95% CI:13.4-16.5%), 2 PCs diagnosed at age >50 years (12.1%, 95% CI: 11.1-13.2%), (p = 0.01). PVs were most frequently identified in: BRCA2 (2.2%) BRCA1 (2.0%), CHEK2 (1.9%) and ATM (1.5%). There were also significant differences in the frequencies of PVs in BRCA1, BRCA2 and MLH1 by sex (p < 0.05). Conclusions: These data demonstrate a high frequency of germline PVs among both males and females with MPC. The frequency of PVs was higher among patients with a higher number of PCs. Differences in the prevalence of PVs by age at cancer diagnosis while significant, were not meaningful as 12.1% of individuals with 2 PCs diagnosed at age >50 years had germline PVs. Limitations include the homogenous testing population (predominately female and white) and small numbers in some patient categories. These data may aid in counseling patients with MPCs and their families as well as encourage less restrictive genetic testing of this population. Further analysis of PV frequencies by specific cancer combinations was conducted and will follow.

Multigene hereditary cancer panel testing for patients with pancreatic cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 244-244
Author(s):  
Anna K McGill ◽  
Sheila R Solomon ◽  
Megan L Marshall ◽  
Lisa Susswein ◽  
Corrine Fillman ◽  
...  
Keyword(s):  
Family History ◽  
Hereditary Cancer ◽  
Diagnostic Yield ◽  
Ductal Adenocarcinoma ◽  
Panel Testing ◽  
Pathogenic Variants ◽  
Gene Panel Testing ◽  
History Of ◽  
Brca1 Brca2 ◽  
Cancer Panel

244 Background: Pancreatic ductal adenocarcinoma (PC) is associated with multiple hereditary cancer syndromes. Genes implicated in hereditary PC include ATM, BRCA1, BRCA2, CDKN2A, EPCAM, MLH1, MSH2, MSH6, PALB2 and PMS2. The advent of multi-gene hereditary cancer panel testing streamlines diagnoses and medical management for clinicians and patients. Our objective was to assess the yield of pathogenic/likely pathogenic variants (PV/LPV) in individuals with PC undergoing panel testing as an initial test at GeneDx. Methods: We retrospectively reviewed panel test results of 605 individuals reporting a personal history of PC. Panel testing evaluated up to 32 genes associated with hereditary cancer. Individuals reporting neuroendocrine pathology or previous BRCA1/BRCA2 testing were excluded. Results: In this cohort, 61 PV/LPV were detected in 57 individuals in the following genes: ATM (17), BRCA2 (14), BRCA1 (5), CDKN2A (5), PALB2 (5), CHEK2 (4), MLH1 (2), MUTYH (2), PMS2 (2), BARD1 (1), FANCC (1), MSH2 (1), RAD51D (1) and TP53 (1), corresponding to a positive yield of 9.4% (57/605). Fifty-one of 61 PV/LPV were detected in genes associated with PC (84%) while 10 PV/LPV (16%) were identified in other genes including BARD1, CHEK2, FANCC, MUTYH, and RAD51D. The diagnostic yield among those reporting a family history of PC (33/294, 11.2%) was not statistically different from those without a reported family history (24/311, 7.7%). However, PV/LPV in ATM were detected more often in individuals reporting a family history of PC compared to those without a family history (4.1% vs. 1.6%, p=0.018). Conclusions: In total, 9.4% of patients with PC tested positive for PV/LPV in 14 different genes by panel testing. Although the majority of PV/LPV were identified in known PC genes, 16% of positive findings occurred in genes not typically associated with PC. ATM was most commonly implicated and more frequently reported in patients reporting family histories of PC. Assessing whether these genes are indeed causally related to PC and/or are possibly associated with other cancer types requires further investigation. Based on our results we conclude multi-gene panel testing may be considered as a first option for patients with PC regardless of their family history.

Sign in / Sign up

Export Citation Format

Share Document