Met National Comprehensive Cancer Network Criteria Research Articles

Outcomes of a universal germline screening program in a community urology practice.

The role of germline genetic testing in urologic oncology has expanded in recent years. However, implementation of genetic testing in community practices remains a challenge, often due to limited access to qualified genetics trained providers. In this study, we report outcomes of a universal germline screening program in a community urology practice. Between November 2021 and September 2022, all patients referred for urology clinic visits at Frederick Health (Frederick, MD, USA) were provided an online genetics screening questionnaire prior to the visit. Responses were compared against National Comprehensive Cancer Network (NCCN) criteria for germline testing. Those who met criteria were provided educational materials at the end of the questionnaire, and then counseled by a trained urologic oncologist (HC) in the clinic or referred to a genetic counselor prior to testing. Testing was performed with a 36-gene pan-cancer panel (CancerNext) or a 14-gene targeted prostate cancer panel (ProstateNext), with or without additional RNA analysis (RNAinsight) (Ambry Genetics, CA, USA). Demographic and clinical parameters, as well as genetic testing results, were retrospectively collected under IRB approval. In the study period, 765 patients were seen over 1370 clinic visits. Of these, 505 patients (66.0%) completed the screening questionnaire. The majority were completed via email (54.5%) with the remainder (45.5%) via text message. Of the patients who completed screening, 125/505 (24.7%) met NCCN criteria for germline testing. 58/125 patients (46.4%) who met criteria underwent germline testing, of whom 5/58 (8.6%) had distinct pathogenic mutations identified. These included actionable mutations in BRCA1, BRCA2, and CHEK2, as well as an additional pathogenic mutation in NBN. Variants of unknown significance were identified in 8/58 patients (13.8%) in 11 total genes. Challenges to implementation of this program included meeting institutional requirements for genetic testing consent, facilitating specimen collection in clinic, and integration of results into the electronic health record. Genetic risk assessment for high-risk individuals is feasible as part of a universal screening program in a community urology practice. Approximately 8% of tested patients were found to have pathogenic germline mutations, which is consistent with contemporary tertiary referral cohorts.

Abstract PO2-08-01: Universal Multi-Gene Panel Testing of Newly Diagnosed Breast Cancer Patients in a Community Healthcare System

Abstract Introduction Multi-gene panel, germline genetic testing has emerged over the last decade as a useful tool in the assessment of hereditary cancer syndromes. As barriers to genetic testing are reduced, offering universal genetic testing to all cancer patients is a practice gaining traction. We present outcomes data specific to the offering of universal, multi-gene panel testing to newly diagnosed breast cancer patients in a community hospital setting. Methods A retrospective chart review was performed for all newly diagnosed breast cancer patients (n=1005) at a community hospital between 8/5/2019 and 8/5/2022. Uptake and outcomes of genetic counseling and genetic testing were assessed. All patients were offered genetic counseling, and those who consented to genetic testing were offered a multi-gene panel (37-93 genes). The National Comprehensive Cancer Network (NCCN) Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic (2020) guidelines were utilized to distinguish which patients met traditional genetic testing criteria. Results Of all newly diagnosed breast cancer patients, 915 (91.1%) patients underwent genetic counseling and 871 (86.7%) patients elected for genetic testing. Of those who declined genetic testing (n=134), 39 (29.1%) reported previous genetic testing. Of patients tested, 489 (56.1%) met NCCN criteria. Overall, 114 (13.1%) of tested patients received results with likely pathogenic/pathogenic (LP/P) variants. Of those, 86 (75.4%) had a clinically significant variant, a high-risk, moderate-risk or another dominantly inherited gene variant, while 28 (24.6%) were identified as genetic carriers; Table 1 summarizes genes with LP/P variants in this cohort, with 10 patients receiving results for 2 variants. Of the patients with clinically significant genetic results, 58 (67.4%) met NCCN criteria. Furthermore, 65 patients (75.6%) reported a family history of cancer relevant to the identified LP/P variant. The average age of the total population, and of those with a positive result, was 62 years. While nearly 19% of all patients tested were under age 50, patients under 50 comprised only 14.0% (n=12) of patients with a clinically significant result. Breast cancer management changes, including addition of a PARP inhibitor to chemotherapy regimen and/or elected bilateral mastectomies in the setting of unilateral disease, were noted in 71.4% (n=20) of patients with high-risk genetic findings and 20.6% (n=7) of patients with moderate-risk genetic findings. Conclusion The 86.7% uptake of genetic testing suggests implementation of universal testing in a community setting is feasible and favored by patients. Clinically significant genetic results would have gone undetected in 32.6% of patients if NCCN criteria was strictly utilized to offer testing. In addition to the 62 patients with high and moderate risk genetic results, utilization of expanded panel testing provided benefit for an additional 24 patients found to have an actionable variant in a gene that would not have been detected on traditional breast cancer panels. Our data supports the offering of genetic testing to all newly diagnosed breast cancer patients, regardless of age, family history, or other criterion, to inform precise breast cancer management and overall, lifetime cancer risks. Genetic Findings of Universal Multi-Gene Panels in a Community Setting Citation Format: Natalie Johns, Jody Wallace, Darbey Raible, Jordan Brady, Grace Miller, Brooke Phillips. Universal Multi-Gene Panel Testing of Newly Diagnosed Breast Cancer Patients in a Community Healthcare System [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-08-01.

Women with pathogenic variants in moderate penetrance breast cancer genes: How frequently do they meet high penetrance genetic testing criteria?

10584 Background: 5-10% of breast cancers are associated with germline pathogenic variants in breast cancer predisposition genes. 2-5% of these variants are in moderate penetrance (MP) genes, conferring a relative risk to develop breast cancer of 2-5. Various personal history (PH) and family history (FH)-based criteria for testing high penetrance genes, such as BRCA1 and BRCA2, have been proposed, but it is unknown to what extent women with pathogenic variants in MP genes may meet such criteria. We evaluated PH and FH of cancer among women with pathogenic variants in MP genes in a diverse and unselected patient cohort in New York City to determine how often they met well-established genetic testing criteria from the National Comprehensive Cancer Network (NCCN). Methods: Exome sequence data from ~16,000 female Bio Me Biobank participants were evaluated for expected pathogenic (per ClinVar, or predicted loss-of-function) variants in ATM, BARD1, BRIP1, CHEK2, NF1, PALB2, RAD51C, and RAD51D. We extracted demographic information, PH and FH of breast, ovarian, and/or pancreatic cancer, and PH and FH of genetic testing from participant questionnaires and electronic medical record review. We then determined which participants met current NCCN criteria (version 1.2023) for high penetrance breast, ovarian, and pancreatic cancer genetic testing. Results: We identified 252 women with expected pathogenic variants in MP genes: 105 CHEK2, 58 ATM, 35 BRIP1, 24 PALB2, 9 BARD1, 8 NF1, 8 RAD51D, and 5 RAD51C. 30% met NCCN criteria, including 30% of those with CHEK2 variants, 36% ATM, 14% BRIP1, 33% PALB2, and 30% with variants in BARD1, NF1, RAD51D, or RAD51C. 36% of those who met NCCN criteria had previously undergone clinical genetic testing. 29 of 33 (88%) women with a PH of breast cancer and 52 of 81 (64%) women with a FH of breast cancer met criteria. Conclusions: Current genetic testing criteria focus on identifying individuals harboring pathogenic variants in high penetrance cancer genes. However, in our study, a substantial portion of women with a pathogenic variant in a MP breast cancer gene also met such criteria, particularly when PH or FH of breast cancer were present. Only a third of those who met NCCN criteria had undergone clinical genetic testing. These findings suggest that the majority of women with genetic risk for breast cancer may be missed in clinical practice. Studies have shown that most physicians would change management strategies for patients with pathogenic variants, including variants in MP genes. As our understanding of genetic risk for breast cancer continues to evolve, we must explore strategies to improve identification and management of individuals with variants in MP breast cancer genes.

PD21-11 REAL WORLD IMPACT OF GERMLINE GENETIC TESTING ON CLINICAL DECISION MAKING FOR PROSTATE CANCER PATIENTS

PD21-11 REAL WORLD IMPACT OF GERMLINE GENETIC TESTING ON CLINICAL DECISION MAKING FOR PROSTATE CANCER PATIENTS

MP54-12 IMPLEMENTATION AND OUTCOMES OF A UNIVERSAL GERMLINE SCREENING PROGRAM IN A COMMUNITY UROLOGY PRACTICE

You have accessJournal of UrologyCME1 Apr 2023MP54-12 IMPLEMENTATION AND OUTCOMES OF A UNIVERSAL GERMLINE SCREENING PROGRAM IN A COMMUNITY UROLOGY PRACTICE Neil Mendhiratta, Herman Hauver, Whitley Hatton, Andrew Ostrusky, Devika Sathe, Patricia Rice, Sandeep Gurram, and Heather Chalfin Neil MendhirattaNeil Mendhiratta More articles by this author , Herman HauverHerman Hauver More articles by this author , Whitley HattonWhitley Hatton More articles by this author , Andrew OstruskyAndrew Ostrusky More articles by this author , Devika SatheDevika Sathe More articles by this author , Patricia RicePatricia Rice More articles by this author , Sandeep GurramSandeep Gurram More articles by this author , and Heather ChalfinHeather Chalfin More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003307.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The role of germline genetic testing in urologic oncology has expanded in recent years. However, implementation of genetic testing in community practices remains a challenge, often due to limited access to qualified genetics trained providers. In this study, we report outcomes of a universal germline screening program in a community urology practice. METHODS: Between August 1st, 2021 and September 19th, 2022, all patients referred for urology clinic visits at Frederick Health (Frederick, MD, USA) were provided an online genetics screening questionnaire prior to the visit. Responses were compared against National Comprehensive Cancer Network (NCCN) criteria for germline testing. Those who met criteria were provided educational materials at the end of the questionnaire, and then counselled by a trained urologic oncologist (HC) in the clinic or referred to a genetic counselor prior to testing. Testing was performed with a 36-gene pan-cancer panel (CancerNext) or a 14-gene targeted prostate cancer panel (ProstateNext), with or without additional RNA analysis (RNAinsight) (Ambry Genetics, CA, USA). Demographic and clinical parameters, as well as genetic testing results, were retrospectively collected under IRB approval. RESULTS: In the study period, 846 patients were seen over 1,580 clinic visits. Of these, 540 patients (63.8%) completed the screening questionnaire. The majority were completed via email (59.7%) with the remainder (40.3%) via text message. Of the patients who completed screening, 136/540 (25.2%) met NCCN criteria for germline testing. 49/136 patients (36%) who met criteria underwent germline testing, of whom 6/49 (12.2%) had distinct pathogenic mutations identified. These included actionable mutations in BRCA1 (c.4616dupT), BRCA1 (c.4964_4982del19), BRCA2 (p.D2723H; c.8167G>C), and CHEK2 (1100delC); additional pathogenic mutations were found in LZTR1 (c.774delT;p.F258Lfs*93) and NBN (p.S706,c.2117c>G). Variants of unknown significance were identified in 8/49 patients (16.3%) in 9 total genes. Challenges to implementation of this program included meeting institutional requirements for genetic testing consent, facilitating specimen collection in clinic, and integration of results into the electronic health record. CONCLUSIONS: Genetic risk assessment for high-risk individuals is feasible as part of a universal screening program in a community urology practice. Approximately 12% of tested patients were found to have pathogenic germline mutations, which is consistent with contemporary tertiary referral cohorts. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e758 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Neil Mendhiratta More articles by this author Herman Hauver More articles by this author Whitley Hatton More articles by this author Andrew Ostrusky More articles by this author Devika Sathe More articles by this author Patricia Rice More articles by this author Sandeep Gurram More articles by this author Heather Chalfin More articles by this author Expand All Advertisement PDF downloadLoading ...

Access disparities and underutilization of germline genetic testing in Chilean breast cancer patients

Latin American reports on genetic cancer risk assessments are scarce. In Chile, current breast cancer (BC) guidelines do not define strategies for germline genetic testing. Our study sought to quantify the disparities in access to genetic testing in Chilean BC patients, according to international standards and their clinical characteristics to explore improvement strategies. Retrospective analysis of invasive BC databases including patients treated in a Public Hospital (PH) and in an Academic Private Center (AC) in Santiago, Chile between 2012 and 2021. Of 5438 BC patients, 3955 had enough data for National Comprehensive Cancer Network (NCCN) categorization. From these, 1911 (48.3%) fulfilled NCCN criteria for germline testing, of whom, 300 were tested for germline mutations and 268 with multigene panels. A total of 65 pathogenic variants were found in this subset. As expected, BRCA1/2 mutations were the most frequent (17.7%). Access to genetic testing was higher in AC versus PH (19.6% vs. 10.3%, p = 0.0001). Other variables associated with germline genetic testing were BC diagnosis after 2018, being 45years old or younger at diagnosis, BC family history (FH), FH of ovarian cancer, non-metastatic disease, and triple-negative subtype. In our cohort, 15% of BC patients who met NCCN criteria for germline testing were effectively tested. This percentage was evenlower at the PH. Current recommendations encourage universal genetic testing for BC patients; however, our findings suggest that Chile is far from reaching such a goal and national guidelines in this regard are urgently needed. To our knowledge, this is the first study of its kind in Chile and Latin America.

Abstract P6-02-03: Breast Health Assessment: A family health history tool using the electronic health record and clinical decision support to facilitate guidelines-driven hereditary breast cancer genetic testing at the time of screening mammogram

Abstract Background: Genetic testing (GT) is recommended for women who have a personal or family history of breast cancer and are at increased risk of carrying an inherited breast cancer risk gene pathogenic variant (PV) as defined by the National Comprehensive Cancer Network (NCCN) guidelines. Data shows that traditional GT workflows do not reach a large proportion of women eligible for GT. NorthShore University HealthSystem previously implemented the Genetic Wellness Assessment, a family health history (FHH) screening tool utilizing the electronic health record (EHR) and clinical decision support, to identify individual and familial risks to health conditions and personalize screening and prevention practices in primary care. To increase access to hereditary breast cancer GT, we implemented a similar FHH screening tool called the Breast Health Assessment (BHA) for patients completing routine screening mammogram. We describe uptake and results from implementation of the BHA in conjunction with routine screening mammogram. Methods: Patients scheduled for screening mammogram were assigned the BHA prior to their mammogram via the EHR portal. BHA questions addressed personal and family history of breast cancer and other cancer types associated with hereditary breast cancer syndromes. Upon completion of the BHA, patients who screened positive, i.e. identified as having a high-risk personal or family cancer history based on NCCN guidelines, were offered a comprehensive hereditary cancer panel (HCP). HCP included 38 genes associated with common cancer types, including all high and moderate risk breast cancer genes for which there are NCCN management guidelines. Individuals who were not identified as high-risk were offered a genetic health screen, which consisted of 148 genes associated with common cancer types, genetic forms of heart disease, medication response, and other health conditions. Saliva sample collection for GT occurred at the time of the patient’s screening mammogram appointment. Results: From August 2021 through May 2022, 32,438 patients were assigned the BHA prior to screening mammogram. Of these patients, 14,128/32,438 (44%) completed the BHA questionnaire. Based on BHA reponse, 3,490/14,128 (25%) screened positive and met NCCN criteria for GT for hereditary breast cancer risk genes and 529/3,490 (15%) completed GT. Additionally, 713/10,638 (7%) patients who screened negative on the BHA completed testing. In total, 1,242/14,128 patients (9%) completed GT and 78/1,242 (6%) were found to carry an inherited PV in a cancer risk gene, 35 of which were in an NCCN guidelines breast cancer risk gene. Of the 78 patients with a positive GT result, 57/78 (73%) had not been previously recommended for a genetics evaluation and/or received a genetics referral. Conclusion: The BHA is a novel FHH tool which increases access to hereditary breast cancer GT at the time of screening mammogram. Nearly half of women who completed screening mammogram completed the BHA and learned valuable information about their breast cancer risk and were invited to complete GT. Genetic testing completed through the BHA identified 78 patients with an actionable inherited PV in a cancer risk gene. This invaluable information will lead to potentially lifesaving personalized cancer screening and risk reduction and help identify additional at risk family members. Notably, 73% of patients who carried an inherited PV had not been previously recommended by their medical teams for genetic counseling and/or testing. The BHA has the potential to help close the care gap in GT for women at increased risk of breast cancer. Citation Format: Allison DePersia, Sarah Choi, Katharine Yao, Henry Dunnenberger, Peter Hulick. Breast Health Assessment: A family health history tool using the electronic health record and clinical decision support to facilitate guidelines-driven hereditary breast cancer genetic testing at the time of screening mammogram [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-02-03.

Missed opportunities in the real-world genetic testing in BRCA gene variant carriers with cancers meeting NCCN criteria

ObjectiveThe objective of this study was to determine the proportion of patients meeting the National Comprehensive Cancer Network (NCCN)’s BRCA genetic testing criteria prior to a diagnosis of a BRCA-related cancer. MethodsThis was a cross-sectional study of patients with BRCA pathogenic variants and a diagnosis of a BRCA-related cancer. Patients were included if they had known dates of genetic testing and cancer diagnosis. NCCN criteria (version 2.2021) were applied to determine if patients met criteria for testing before a BRCA-related cancer diagnosis. The outcome of interest was the proportion of patients undergoing genetic testing following a diagnosis of a BRCA-related cancer who qualified for genetic testing based on NCCN criteria. Chi-square, Mann-Whitney U test, and logistic regression were performed with significance at p < 0.05. ResultsOf 270 patients with a BRCA-related cancer, 229 (85%) underwent genetic testing after a cancer diagnosis. Most patients (97%) met at least one NCCN criteria for BRCA testing; 166 (73%) of patients who were tested following a BRCA-related cancer diagnosis also met the criteria for testing by family history. Publicly insured or uninsured patients were three times more likely to undergo BRCA testing after a diagnosis of cancer (odds ratio [OR] 3.03, 95% confidence interval [CI] 1.09–8.40). Patients with a family history of pathogenic variants were more likely to undergo testing before a cancer diagnosis (OR 0.10, 95% CI 0.05–0.23). ConclusionMost patients with BRCA-associated cancers undergo genetic testing after their cancer diagnosis. Increased education on genetic testing criteria and novel methods to improve testing are desperately needed.

Abstract P043: A precision medicine gap: limited recognition of colorectal patients eligible for germline testing in molecular residual disease testing setting

Abstract Background: Germline testing for hereditary colorectal cancer (CRC) has traditionally been offered to patients with strong cancer family histories, whose colon tumors revealed mismatch repair deficiency (dMMR), and/or individuals diagnosed with CRC under age 50. Underdiagnosis of hereditary cancer syndromes is often attributed to the complexity or unawareness of family history or phenotypic criteria.1,2 The National Comprehensive Cancer Network (NCCN) guidelines for CRC were recently updated (v. 1.2022) to consider germline multigene panel testing (MGPT) evaluation for all individuals with CRC.3,4 Our goal was to evaluate documentation of MGPT in CRC patients referred for molecular residual disease (MRD) testing. Methods: This retrospective cohort study reviewed clinical data submitted to a commercial laboratory for consecutive CRC patients referred from non-academic medical facilities for MRD testing during a two-month study period. Medical diagnoses, treatment history, family history and germline genetic evaluation status were obtained from the test requisition form and pathology reports. Clinical notes were reviewed in 77/80 cases. Results: Of the 80 patients who met criteria for inclusion, 65/80 (81%) had documented MMR testing of their colorectal tumor. Whereas five had abnormal immunohistochemistry, only two (40%) had documented germline results. 19/80 (24%) met NCCN criteria solely based on a personal CRC diagnosis &amp;lt;50 years, but only 1/19 (5.3%) had documented MGPT. Only 5/80 (6%) of all CRC patients had documented MGPT. Conclusion: Our real-world data from the community oncology precision medicine setting suggests that a majority of CRC patients who received MRD testing and met the prior NCCN criteria for MGPT may not have received evaluation beyond routine MMR status. Process and educational improvements are needed in community health settings to increase access and uptake of germline testing in CRC patients regardless of age at diagnosis or MMR status. Citation Format: Suzanne Schrock-Kelley, Vivienne Souter, Michael Hall, Jeffrey N. Weitzel. A precision medicine gap: limited recognition of colorectal patients eligible for germline testing in molecular residual disease testing setting. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr P043.

Cancer risk assessment models versus National Comprehensive Cancer Network guidelines: What is the most comprehensive method to assess cancer risk and triage for genetic testing? (373)

Cancer risk assessment models versus National Comprehensive Cancer Network guidelines: What is the most comprehensive method to assess cancer risk and triage for genetic testing? (373)

Implementation of universal, pan-cancer germline genetic testing in patients with cancer in Jordan.

10580 Background: Detection of pathogenic germline variants (PGVs) has a significant and growing impact on the management of patients with many types of cancer. Most research to date evaluated individuals of European background, which can result in skewed genetic testing criteria and variant interpretation. Additional data are needed from diverse populations. This study aimed to investigate a universal germline testing strategy and the pattern and frequency of PGVs among all newly diagnosed cancer patients at a single center in Jordan. Methods: In this prospective, observational study, consecutive patients newly diagnosed with cancer were classified as meeting or not meeting National Comprehensive Cancer Network (NCCN) germline genetic testing criteria. All patients underwent an 84-gene panel test, independent of age, stage or family history. Demographics and clinical history were collected and analyzed from information provided by the clinicians on the test requisition form. Descriptive statistics were employed, and statistical significance was determined by two-tailed Fisher’s exact test and unpaired t test. Results: In total, 1377 cancer patients of Arabic background were enrolled, of which 831 (60.3%) met NCCN criteria (Table). PGVs were identified in 210 (15.3%). Excluding the 29 patients who were carriers for autosomal recessive conditions, 192 PGVs were identified in 181 (13.1%) patients. PGVs were most commonly identified in APC (p.I1307K variant, 55, 28.6%), BRCA2 (35, 18.2%), BRCA1 (21, 10.9%), and TP53 (12, 6.3%). While patients who met NCCN testing criteria were more likely to have a PGV (p&lt;0.0001), 44 (24.30%) patients with PGVs did not meet criteria. Among those with PGVs, 177 (97.8%) were potentially eligible for increased screening per NCCN/expert opinion guidelines, 69 (38.1%) targeted therapies, and 89 (49.2%) clinical trials; this included 41 (22.7%), 6 (3.3%), and 14 (7.7%) patients, respectively, that did not meet NCCN testing criteria. 1445 variants of uncertain significance (VUS) were identified in 833 (57.7%) patients, but no difference in VUS rate was observed between those meeting and not meeting criteria (p=0.7354). Conclusions: Overall PGV rate among cancer patients from one center in Jordan was similar to that reported in the literature. While the VUS rate was high, similar rates were observed in those meeting and not meeting criteria. Testing restricted to guidelines could have missed approximately a quarter of patients with PGVs, &gt;95% of whom might qualify for increased screening, targeted therapies, and/or clinical trials. [Table: see text]

Democratizing germline genetic testing and its impact on prostate cancer clinical decision-making.

10500 Background: Approximately 10-15% of prostate cancer (PCa) patients (pts) have a pathogenic germline variant (PGV). Identification of a PGV has important implications affecting decisions regarding cancer screening, treatment selection, and family cascade testing. There exists limited data documenting real world recommendations post germline genetic testing (GGT). This study was designed to collect clinician reported outcomes from PCa pts who underwent GGT. Methods: An IRB-approved, nationwide, prospective registry recruited unselected PCa pts from 15 community and academic urology practices. Pts underwent an 84-gene panel test, with clinical outcomes collected via clinician-completed case report forms &gt; 1-month post GGT. Statistical significance was determined by two-tailed Fisher’s exact test. Results: 982 predominantly white (75.9%), non-metastatic (80.7%) males with PCa were recruited; 56.9% met National Comprehensive Cancer Network (NCCN) GGT criteria. Average age was 65.3 years at PCa diagnosis. PGVs, most commonly CHEK2 (17) and BRCA2 (10), were identified in 100 (10.2%) pts; 34 (34%) of these did not meet NCCN GGT criteria. Among PGV positive pts, 241 recommendations were made (Table). They were more likely to have changes to treatment (p &lt; 0.0001), follow up (p &lt; 0.0001) and cascade testing recommendations (p &lt; 0.0001) than those with negative/variant of uncertain significance (VUS) results. There were no significant differences in changes to treatment (p = 0.4471) or follow up (p = 0.861) for pts who met NCCN criteria versus those who did not. 7 pts with PGVs received targeted therapy or were referred to a clinical trial. 5 pts with VUS results were also referred to a clinical trial. Among these 12 pts, 6 (50%, 2 CHEK2 PGV, 1 ATM PGV, 1 VUS each ATM, BLM, CHEK2) did not meet NCCN GGT criteria. Referral to a genetic counselor was the most common follow up recommendation for those with PGV (38 patients, 38%) and VUS results (66, 13.7%). The most commonly reported impact to health outcomes for those with negative results was knowledge/reassurance (38, 7.88%). Conclusions: This study showed that GGT did influence PCa pts care. Appropriately, pts with PGVs received a greater number of recommendations for relatives, changes to follow up and treatment. [Table: see text]

Genetic risk assessment in primary care settings: An evaluation of NCCN guidelines.

10605 Background: Lynch syndrome (LS) and hereditary breast and ovarian cancer (HBOC) have a population prevalence of 1/2791 and 1/4002, respectively. Despite this, &gt;80% of patients referred for cancer genetic counseling report personal or family history of breast cancer3. This disparity may be due to increased media attention for HBOC, lower levels of provider awareness of LS, and less discussion of colorectal cancer within families compared to breast cancer4. However, potential biases in National Comprehensive Cancer Network (NCCN) criteria for genetics evaluation (GE) have not been studied. This project examined the performance of NCCN guidelines for identifying individuals meeting criteria for GE ascertained through primary care (PC) settings. Methods: Individuals scheduled for routine PC appointments at three Michigan Medicine affiliated practices from 10/24/18 through 1/24/22 were emailed a link to complete an online personal and family history (P/FHx) risk assessment module (INHERET) collecting information about cancer diagnoses (age/cancer type) in 1st, 2nd, and 3rd degree relatives. The module was written at a 4th grade reading level and could be accessed on any internet-connected device. NCCN guidelines were applied to determine if patients met criteria for GE of HBOC and/or LS. Results: A total of 465 individuals completed the module; nearly one in three (30.6%, 142/465) met NCCN criteria for GE of HBOC or LS. Of those meeting criteria, 132 (92.9%) had no personal history of cancer. The most common indication for GE was HBOC (29.5%, 137/465) and 30 patients (6.5%) met HBOC referral criteria solely based on Ashkenazi Jewish ancestry. Only 17/465 (3.7%) individuals met NCCN criteria for GE of LS. Interestingly, 12/17 (70.6%) who met criteria for GE of LS also met criteria for GE of HBOC. The completion rate was not 100% and cannot be determined; it is not known how many patients were offered the option of completing the module. This limits the study, as ascertainment bias cannot be assessed. Conclusions: Nearly one-third of PC patients who completed the P/FHx module met NCCN criteria for genetic evaluation of HBOC and/or LS. Referrals for HBOC outnumber those for LS, even though LS is just as common1, 2, 3. Further evaluation of NCCN criteria is needed to evaluate whether patients may be over-referred for HBOC and/or under-referred for LS. Unfortunately, we were not able to confirm receipt of email invitations or accurately calculate completion rate of the P/FHX risk assessment module, which limited our ability to assess for ascertainment/response bias. [Table: see text]

Demographic Barriers for Genetic Testing in High-Risk Breast Cancer Patients in the Northern Michigan Area.

Introduction: The National Comprehensive Cancer Network (NCCN) has outlined guidelines for criteria regarding genetic testing for high-penetrance breast and/or ovarian cancer susceptibility genes. Due to the lack of availability of genetic counseling services in Northern Michigan prior to COVID-19, the utilization of genetic testing falls well below recommended guidelines.Methods: Patients diagnosed with breast cancer in 2019 were randomly selected from Ascension Michigan's Northern Ministries Tumor Registry. A retrospective chart review was conducted. For patients who met NCCN criteria, their medical records were used to determine if genetic testing was recommended and if genetic testing was completed. Univariate (Crosstabs and t-tests) and multivariate tests with logistic regression were used to identify significant associations between the variables of interest.Results: One hundred and two (102) patient charts were reviewed in this group; 55 (52.4%) were eligible by the NCCN guidelines for genetic testing. From this eligible subset of patients, only 29 were offered genetic testing, and only 21 were tested. The mean age of the patients offered genetic counseling was 56.2 years compared and 67.6 years in the group not offered counseling (p < 0.001). The patient's insurance type was an independent factor for obtaining genetic testing, specifically, the subgroup who had Medicare (OR = 0.73, CI = 0.01-0.54; p = 0.02). Patients insured through Medicare were less likely to obtain genetic testing after referral to a genetic counselor (p = 0.01).Conclusion: Genetic counseling for high-risk breast cancer patients is below average in Northern Michigan, likely related to lack of physician referral, poor availability of counseling services, low socioeconomic status as well as a lower level of concern in older ages.

Missed Opportunities? An Observational Analysis of Lung Cancer Screening Utilization Amongst Patients With Lung Cancer.

Lung cancer (LC) is the leading cause of cancer-related deaths worldwide. The U.S. Preventive Services Task Force (USPSTF) and National Comprehensive Cancer Network (NCCN) recommend annual low-dose CT chest (LDCT) for LC screening in high-risk adults who meet appropriate criteria, which primarily focus on age and smoking history. Despite this, screening rates remain low and patients with LC are typically diagnosed at a later stage.We conducted a single-center retrospective analysis of patients with an established diagnosis of lung cancer to evaluate if screening guidelines were appropriately followed before the cancer diagnosis.Patients diagnosed with LC between 2016 and 2019 were included in the analysis. Charts were reviewed for demographics, detailed smoking history, as well as histology and stage of LC. Associations between categorical factors and screening were examined using the chi-square test. Associations between continuous and ordinal factors and screening were examined using the Mann–Whitney test.A total of 530 charts were reviewed, of which 52% met NCCN criteria and 35% met USPSTF criteria. Only 4.0% and 4.8% of patients who met NCCN and USPSTF criteria, respectively, underwent screening. There was a significant association between staging at diagnosis and screening with LDCT. All the patients who had screening CT scans were diagnosed at localized stages of lung cancer in both NCCN and USPSTF groups compared to 49.1% and 48% in eligible subjects that did not undergo screening, respectively.Our study showed that despite established guidelines for LC screening and insurance coverage, a vast majority of screening-eligible LC patients have never had LDCT. We found that patients who underwent screening as per guidelines were diagnosed at earlier stages of the disease. Ongoing efforts to increase awareness and adherence to LC screening guidelines are needed to improve early detection and reduce LC mortality.

Compliance with sentinel lymph node biopsy guidelines for invasive melanomas treated with Mohs micrographic surgery.

Sentinel lymph node biopsy (SLNB) has not been studied for invasive melanomas treated with Mohs micrographic surgery using frozen-section MART-1 immunohistochemical stains (MMS-IHC). The primary objective of this study was to assess the accuracy and compliance with National Comprehensive Cancer Network (NCCN) guidelines for SLNB in a cohort of patients who had invasive melanoma treated with MMS-IHC. This retrospective cohort study included all patients who had primary, invasive, cutaneous melanomas treated with MMS-IHC at a single academic center between March 2006 and April 2018. The primary outcomes were the rates of documenting discussion and performing SLNB in patients who were eligible based on NCCN guidelines. Secondary outcomes were the rate of identifying the sentinel lymph node and the percentage of positive lymph nodes. In total, 667 primary, invasive, cutaneous melanomas (American Joint Committee on Cancer T1a-T4b) were treated with MMS-IHC. The median patient age was 69years (range, 25-101years). Ninety-two percent of tumors were located on specialty sites (head and/or neck, hands and/or feet, pretibial leg). Discussion of SLNB was documented for 162 of 176 (92%) SLNB-eligible patients, including 127 of 127 (100%) who had melanomas with a Breslow depth >1mm. SLNB was performed in 109 of 176 (62%) SLNB-eligible patients, including 102 of 158 melanomas (65%) that met NCCN criteria to discuss and offer SLNB and 7 of 18 melanomas (39%) that met criteria to discuss and consider SLNB. The sentinel lymph node was successfully identified in 98 of 109 patients (90%) and was positive in 6 of those 98 patients (6%). Combining SLNB and MMS-IHC allows full pathologic staging and confirmation of clear microscopic margins before reconstruction of specialty site invasive melanomas. SLNB can be performed accurately and in compliance with consensus guidelines in patients with melanoma using MMS-IHC.

One size does not fit all: Evaluating disparities in lung cancer screening eligibility amongst Hispanic/LatinX and African Americans.

6538 Background: Lung cancer (LC) is the leading cause of cancer death among Hispanic men. African Americans (AA) have the highest LC mortality rate in the United States (US). We sought to identify the tendencies for screening eligibility amongst Hispanic/LatinX (H/L) and AA prior to their LC diagnosis according to the National Comprehensive Cancer Network (NCCN) and The United States Preventive Service Task Force (USPSTF) guidelines. Methods: We conducted an observational study in patients diagnosed with LC from 2016 to 2019. Current and former smokers were included in the analysis. Charts were reviewed for demographics, smoking history, family history, personal history of other malignancy, and prior exposures to assess screening their eligibility prior to LC. The chi-square test was used to examine the association between race and ethnicity with each screening criteria. Results: A total of 530 subjects were reviewed, of which 428 were included in the analysis. One hundred and fifty three and 245 subjects were ineligible for NCCN and USPSTF screening criteria prior to their LC diagnosis. Twenty-eight of the subjects failing to meet NCCN criteria identified as AA and 12 as H/L. Forty and 20 of the USPSTF ineligible subjects identified as AA and H/L. There was a significant association between ethnicity and individual screening eligibility, where 52% of H/L met NCCN eligibility compared to 20% of H/L who met USPSTF eligibility (p = 0.0010). There was a significant association between ethnicity and USPSTF criteria (p = 0.0166), as 80% of H/L subjects were screening ineligible under USPSTF criteria compared to 56% of non-Hispanic or other [Table]. Conclusions: In our study, H/L had significant lower tendencies of meeting the USPSTF LC screening eligibility criteria than non-H/L or other. Notably, there was a profound association between ethnicity and eligibility of screening criteria, where a proportionally higher number of H/L who were ineligible under USPSTF criteria met NCCN criteria. These findings suggest that leniency in the screening criteria can possibly lead to earlier detection of lung cancer in high-risk individuals. Our study is in line with developing data that minority individuals at high-risk for lung cancer can be missed, mainly if current USPSTF criteria was to be applied. Recently, USPSTF has modify their criteria which may benefit more of these individuals. To improve rates of screening and overall mortality of minorities, organizations should continue to re-evaluate and liberalize their screening guidelines.[Table: see text]

Use of comprehensive next-generation sequencing to identify pathogenic germline variants with therapeutic relevance in metastatic breast cancer.

10527 Background: Among patients with early-stage breast cancer, approximately 6-10% have a pathogenic germline variant (PGV) conferring inherited cancer predisposition. In contrast, few studies have explored the frequency and types of PGVs identified in patients with metastatic breast cancer (MBC); therefore, additional data is needed. Methods: From 2011-2020, 278 patients with MBC underwent fresh tumor biopsy and blood sample collection for paired tumor/normal DNA (targeted exome capture with analysis of 1700 genes) and RNA (tumor transcriptome) sequencing through the Michigan Oncology Sequencing (Mi-ONCOSEQ) program. Somatic and germline alterations were annotated and classified according to degree of clinical actionability with results returned to treating oncologists. Retrospective chart review was performed to determine if: 1) a PGV was identified prior to Mi-ONCOSEQ testing, 2) patients met National Comprehensive Cancer Network (NCCN) guideline criteria for genetic testing on the basis of personal or family cancer history and 3) patients received subsequent therapy informed by a PGV. Results: Forty-eight of the 278 patients (17.3%) had at least one PGV identified, with a total of 50 PGVs identified in this cohort. Only twelve of these PGVs (24%) had been identified prior to Mi-ONCOSEQ testing. The most frequent PGVs identified were in CHEK 2 (n = 9, 18%), MUTYH (n = 6, 12%), BRCA 1 (n = 5, 10%), BRCA2 (n = 5, 10%), ATM (n = 4, 8%) and PALB2 (n = 4, 8%). Somatic loss of heterozygosity events (LOH) occurred in 30 of the 50 cases with PGVs identified (60%). LOH events were observed in 83.3% of BRCA1, BRCA2, ATM and PALB2 PGVs, but were less frequently observed with CHEK2 (33.3%) and MUTYH (66.7%). Two hundred sixteen out of 278 patients (77.7%) in this cohort met NCCN criteria for genetic testing, although six patients with a PGV identified (CHEK2: n = 5; MUTYH: n = 1) did not meet NCCN criteria. Twenty-nine PGVs identified (58%) had potential therapeutic relevance and 11 patients (22.9%) received targeted therapy based on the PGV. Conclusions: The frequency of PGVs identified in this cohort is nearly double the frequency reported for patients with early-stage disease, suggesting that certain PGVs may confer worse prognosis. CHEK2, the most frequently identified PGV, was less likely to have an identifiable LOH event. The direct role of CHEK2 PGVs in tumor pathogenesis is uncertain, but other mechanisms of silencing the wild type allele must be considered. Despite the majority of patients meeting NCCN criteria for genetic testing, those with PGVs in CHEK2 were less reliably identified by this mechanism. The majority of PGVs identified were of potential therapeutic relevance, supporting the recommendation for genetic testing in all patients with MBC.

Abstract PS7-20: Identification of pathogenic mutations in otherwise unaffected patients through the CARE program

Abstract Introduction Approximately one out of eight women are diagnosed with breast cancer in their lifetime. Women are recommended to begin annual mammograms at age 40 unless they are high-risk risk for breast cancer based on risk algorithms or positive germline mutations. Unfortunately, genetic testing and risk counseling are often not offered until a cancer diagnosis is already made. It is estimated that 5-10% of the general population has genetic predisposition to cancer. Purpose We established the Comprehensive Assessment, Risk &amp; Education (CARE) Program at our mammogram center. Offered in partnership with Ambry Genetics, the CARE Program’s goal is to facilitate unaffected women in obtaining genetic testing and risk-counseling who otherwise may not have access to these services. Methods Patients undergoing a screening mammogram were given a tablet with a preprogrammed Progeny questionnaire. This questionnaire included questions on the patient’s gynecological history and family history. It calculates a Tyrer-Cuzick risk score and assesses National Comprehensive Cancer Network (NCCN) genetic testing criteria. Patients qualifying for genetic testing received pretest counseling by video and were offered genetic testing the same day as their mammogram appointment. Our genetic counselors performed follow-up counseling for patients receiving positive test results. Patients testing negative or inconclusive received a letter generated by Ambry. Our CARE program began on June 7th, 2019, and data was assessed through July 6th, 2020. Results 1,065 women met NCCN criteria for genetic testing. Of those women, 464 (43.6%) proceeded with testing, 387 (36.3%) declined testing and 214 (20.1%) were not able to obtain day-of genetic testing due to operational/personnel limitations. Of those who submitted tests, 403 (86.9%) completed testing and 61 tests were cancelled due to out of pocket costs or patient preference. Of the 403 patients who completed testing, 262 (65%) tested negative, 105 (26%) tested inconclusive and 35 (8.7%) tested positive. Positive test results were found in 15 genes (Table 1). Clinical Impact Over 13 months, we identified 35 patients at increased risk for cancer based on positive genetic test results. Based on these results, 6 (17%) patients were offered prophylactic surgeries, 16 (45.7%) were offered breast MRIs and enrollment in our high-risk breast clinic, 14 (40%) were offered increased colonoscopies and 9 (25.7%) were offered pancreatic screening based on family history. All patients were offered family variant testing. Conclusion Our experience integrating a screening questionnaire into our mammogram clinic shows that 44% of patients meeting NCCN criteria agree to do day of testing. Of those completing testing, 9% tested positive. This result is consistent with the national expected positive rate. Our CARE Program offers unaffected patients an opportunity to be tested in a comfortable low stress setting through the mammography suite. These patients and their families will now benefit from cancer prevention options that may not have been offered to them had they not been pre-emptively screened by our program. Table1. Positive test results for 35 patients.MutationNumber of patients identified (%)CHEK29 (25.7)MUTYH5 (14.2)HOXB134 (11.4)ATM3 (8.6)APC2 (5.7)BARD12 (5.7)PALB22 (5.7)BRCA21 (2.9)BRIP11 (2.9)MRE11A1 (2.9)MSH21 (2.9)MSH61 (2.9)RAD501 (2.9)RAD51D1 (2.9)TP531 (2.9) Citation Format: Lida Mina, Rebecca Luiten, Jennifer Siettmann, Vilert Loving. Identification of pathogenic mutations in otherwise unaffected patients through the CARE program [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-20.

Adherence to National Comprehensive Cancer Network Guidelines for BRCA testing among high risk breast Cancer patients: a retrospective chart review study

BackgroundTesting for BRCA variants can impact treatment decisions for breast cancer patients and affect surveillance and prevention strategies for both patients and their relatives. National Comprehensive Cancer Network (NCCN) guidelines recommend testing for patients at heightened risk of BRCA pathogenic variant. We examined the BRCA testing rate among high risk breast cancer patients treated in community oncology practices.MethodsWe conducted a retrospective medical chart review among community-based US oncologists using a physician panel approach. High risk breast cancer patients with a known family history of cancer and diagnosis with breast cancer at age ≥ 18 years between January 2013–October 2017 were included. We assessed the proportions of patients tested for BRCA variants in accordance with NCCN guidelines.ResultsCharts from 63 physicians, averaging 16 years of practice, were included; 97% were medical oncologists and 66.7% had a genetic counselor in their practice. We analyzed data for 410 randomly-selected patients with mean age of 52 years; 95% were female, 74% were White, and 19% had Ashkenazi Jewish ancestry. Among all patients, 94% were tested for BRCA variants. The testing rate ranged from 78 to 100% in various high risk groups; lower rates were observed among Black patients (91%), men (92%), and patients meeting NCCN criteria based on family history of male breast cancer (78%) and prostate cancer (87%). We observed a higher testing rate in patients treated by physicians with a genetic counselor in their practice (95% versus 91%).ConclusionsAdherence to NCCN BRCA testing guidelines is high in this group of predominantly medical oncologists with extensive experience, with a high proportion having a genetic counselor in practice. Testing rates can be improved in patients with risk factors related to male relatives. High level of compliance to guidelines in a community setting is possible with a delivery model for genetic counseling and testing.