Genetic Testing Among Breast Cancer Patients in the Eastern Region of Saudi Arabia: Single-Center Experience.

BACKGROUND: Genetic testing for persons with a heightened likelihood of harboring a germline mutation permits early identification and appropriate management. This study aimed to identify the proportion of breast cancer (BC) patients who were offered genetic testing and the prevalence of BRCA mutations among them. Additionally, we assessed the demographic and clinical features of BC patients in the Eastern Region of Saudi Arabia. MATERIALS AND METHODS: Data from 2535 patients with BC were retrieved from the registry between 2017 and 2021. The data were analyzed and presented using univariate and bivariate statistics. Odds ratios and 95% confidence intervals using logistic regression analysis were computed to identify the predictors of BRCA testing. RESULTS: Patients with BC ranged in age from 18 to 103 years, and the mean age was 49.60 ± 12.14 years. BC was detected in men in 29 (1.1%) cases. Among diagnosed patients with BC, a total of 96 (3.7%) patients underwent testing for BRCA gene mutations. Of them, 36 (37.5%) patients had a BRCA gene mutation. The likelihood of undergoing BRCA testing was higher for those who were diagnosed with the condition before the age of 50, patients who were referred from private institutions, and patients with a history of previously diagnosed cancer. The likelihood of conducting BRCA testing was significantly lower among those with distant metastases. CONCLUSION: The proportion of BRCA testing among BC patients was found to be relatively low. The development of a cost-effective, locally developed risk assessment tool that incorporates genetic counseling and testing for those with a familial predisposition to BC is imperative.

BRCA Testing for Patients Treated in Italy: A National Survey of Breast Centers Associated with Senonetwork.

BACKGROUND: Breast units (BUs) provide breast cancer (BC) care, including prevention, treatment, and genetic assessment. Genetic research has highlighted BRCA1/2 mutations as key hereditary BC risk factors. BRCA testing is crucial for personalized treatment and prevention strategies. However, the integration of BRCA testing in Italian BUs faces multiple challenges. This study, by Senonetwork Italia, aimed to evaluate genetic testing practices and identify obstacles within Italian BUs. METHODS: Senonetwork Italia conducted a 16-question web-based survey involving 153 BUs. The survey assessed aspects of BRCA testing, including timing, urgency, counseling, patient selection, and multi-gene panels. RESULTS: Of the 153 BUs, 109 (71.2%) responded. Testing before surgery was performed by 70.6% of centers, with urgent cases acknowledged by 87.2%. Most centers (56.0%) arranged urgent pre-test counseling within a week. BRCA mutation status influenced treatment decisions in 99.1% of cases. Multi-gene panels were used by 33.0% of centers for all genetic counseling cases, while 56.0% followed standard referral criteria. The main challenges included cost, reimbursement, and reporting timelines. CONCLUSIONS: This survey highlights significant variations in BRCA testing practices across Italian BUs and identifies key logistical and financial challenges. There is a need for standardized practices of genetic testing to ensure personalized and effective BC management in Italy.

Intersectionality, BRCA Genetic Testing, and Intrafamilial Communication of Risk: A Qualitative Study.

Significant health disparities exist in relation to pathogenic variants in BRCA1/2. This study aimed to better understand the barriers and facilitators to BRCA1/2 genetic testing and intrafamilial communication of risk in racially and ethnically diverse individuals. We conducted qualitative interviews with non-Hispanic White (n = 11) and Black, Indigenous, People of Color (BIPOC) individuals (n = 14) who underwent testing for pathogenic BRCA1/2 variants. We employed template analysis, case study analysis, and comparative case study analysis to examine healthcare experiences related to genetic testing as well as intrafamilial communication of risk. Applying an intersectional lens, we sought to inform more person-centered approaches to precision healthcare and help dismantle disparities in genomic healthcare. Template analysis revealed salient factors at the individual (psychosocial well-being), interpersonal/familial, and healthcare system levels. A two-part case study analysis provided insights into how race/ethnicity, cultural norms, and socioeconomic status interact with systemic and structural inequities to compound disparities. These findings underscore the need for person-centered, tailored, and culturally sensitive approaches to understanding and addressing the complexities surrounding testing and the communication of BRCA risk. Applying an intersectional lens can inform more person-centered approaches to precision healthcare and may help to surmount existing disparities.

The impact of an educational and information systems initiative on somatic BRCA testing rates in patients with high grade serous tubo-ovarian cancer in Western Australia.

Objective: Poly-ADP ribose polymerase inhibitors (PARPi) have expanded the management armamentarium against high grade serous tubo-ovarian cancer (HGSOC) in patients with germline and somatic BRCA pathogenic variants (PVs). Germline testing has been available in Western Australia (WA) since July 2015, whilst somatic BRCA testing was previously only available through interstate laboratories. We hypothesized that due to complexity of referral, testing rates for somatic BRCA would be low. We aimed to demonstrate that improving education and information systems would improve testing rates in our service. Methods: Retrospective data were collected for all patients with HGSOC reviewed between June - November 2021. BRCA testing for this period was discussed at multi-disciplinary tumor board. Patients eligible to commence PARPi that had not received somatic testing were referred. Changes were implemented to patient outcome reports, the results application was adjusted to flag clinicians, departmental guidelines were developed, and teaching sessions conducted. Testing rates from March - August 2022 were compared. Results: From June - November 2021, 98% of patients had germline BRCA testing performed. PVs in BRCA1/2 were detected in 18% of patients. Of those without germline PVs, further somatic BRCA testing was referred in 42% of patients. One somatic PV was detected. From March - August 2022, 99% of patients had germline BRCA testing and 17% had PVs detected. Further somatic BRCA testing was referred in 72% of patients. No somatic PVs were detected. Conclusion: Testing rates for germline BRCA variants in patients with HGSOC in WA are high. Focused education and information systems improved somatic BRCA testing rates.

Impact of lower co-payments on risk-reducing salpingo-oophorectomy and BRCA testing in Japan.

BACKGROUND: In April 2020, insurance coverage for risk-reducing salpingo-oophorectomy (RRSO) for breast cancer patients with hereditary breast and ovarian cancer (HBOC) syndrome and BRCA testing were started in Japan. We investigated the impact of insurance coverage on the number of RRSO and BRCA tests performed. METHODS: The subjects were 370 breast cancer patients and 23 of their relatives who received genetic counseling at our institution between April 2014 and December 2021. Finally, 349 patients and 15 relatives were analyzed. We retrospectively compared the number of BRCA tests, RRSO, insurance status, and co-payment of medical expenses before and after insurance coverage based on medical records. RESULTS: In the 6-year pre-coverage period, 226 patients (mean: 37/year) received genetic counseling and 106 (17/year) received BRCA testing. In the 21-month post-coverage period, 161 patients (92/year) received genetic counseling and 127 (72/year) received BRCA testing. The rate of testing/counseling significantly increased in the post-coverage period (46.9% vs. 78.8%; p < .001). The number of patients who were diagnosed with HBOC were 24 (4/year) and 18 (10/year) and RRSO was performed for 7 (1/year) and 11 (6/year) patients in the pre- and post-coverage periods, respectively. The rate of RRSO/HBOC was significantly increased in the post-coverage period (29.1% vs. 61.1%; p = 0.039). RRSO patients' co-payment rates decreased from 64% to 25% pre- and post-coverage. CONCLUSIONS: Our findings suggest that decreased co-payments were the primary reason for these increases. Insurance coverage is an important factor when promoting preventive medical services such as RRSO.

Cost-Effectiveness Analysis of Germline and Somatic BRCA Testing in Patients With Advanced Ovarian Cancer.

Background: BRCA testing is necessary for establishing a management strategy for ovarian cancer. Several BRCA testing strategies, including germline and somatic testing, are implemented in clinical practice in Korea. We aimed to comparatively evaluate their cost-effectiveness from patients' perspective. Methods: We developed a decision model comprising five BRCA testing strategies implemented in Korea: (1) germline testing first, followed by somatic tumor testing for patients without a germline variant; (2) somatic testing first, followed by germline testing for patients with a variant detected by somatic testing; (3) both germline and somatic testing; (4) germline testing alone; and (5) somatic testing alone, with no testing as the comparator. One-way sensitivity analysis was conducted to test the uncertainty of key parameters. Results: Assuming a willingness-to-pay of $20,000 per progression-free life-year gain (PF-LYG), all five strategies were considered cost-effective. Strategy 4 was the most cost-effective option, with an incremental cost-effectiveness ratio (ICER) of $2,547.7 per PF-LYG, followed by strategy 1, with an ICER of $3,978.4 per PF-LYG. Even when the parameter values were varied within the possible range, the ICERs of all strategies did not exceed the willingness-to-pay threshold. Conclusions: Considering the importance of knowing a patient's BRCA gene status, germline testing first, followed by somatic testing, may be a reasonable option.

Laboratory Cross-Comparison and Ring Test Trial for Tumor BRCA Testing in a Multicenter Epithelial Ovarian Cancer Series: The BORNEO GEICO 60-0 Study.

Germline and tumor BRCA testing constitutes a valuable tool for clinical decision-making in the management of epithelial ovarian cancer (EOC) patients. Tissue testing is able to identify both germline (g) and somatic (s) BRCA variants, but tissue preservation methods and the widespread implementation of NGS represent pre-analytical and analytical challenges that need to be managed. This study was carried out on a multicenter prospective GEICO cohort of EOC patients with known gBRCA status in order to determine the inter-laboratory reproducibility of tissue sBRCA testing. The study consisted of two independent experimental approaches, a bilateral comparison between two reference laboratories (RLs) testing 82 formalin-paraffin-embedded (FFPE) EOC samples each, and a Ring Test Trial (RTT) with five participating clinical laboratories (CLs) evaluating the performance of tissue BRCA testing in a total of nine samples. Importantly, labs employed their own locally adopted next-generation sequencing (NGS) analytical approach. BRCA mutation frequency in the RL sub-study cohort was 23.17%: 12 (63.1%) germline and 6 (31.6%) somatic. Concordance between the two RLs with respect to BRCA status was 84.2% (gBRCA 100%). The RTT study distributed a total of nine samples (three commercial synthetic human FFPE references, three FFPE, and three OC DNA) among five CLs. The median concordance detection rate among them was 64.7% (range: 35.3-70.6%). Analytical discrepancies were mainly due to the minimum variant allele frequency thresholds, bioinformatic pipeline filters, and downstream variant interpretation, some of them with consequences of clinical relevance. Our study demonstrates a wide range of concordance in the identification and interpretation of BRCA sequencing data, highlighting the relevance of establishing standard criteria for detecting, interpreting, and reporting BRCA variants.

Evaluating the Effectiveness of a Telehealth Cancer Genetics Program: A BRCA Pilot Study.

INTRODUCTION: Ashkenazi Jewish (AJ) individuals face a 1 in 40 (2.5%) risk of having a BRCA mutation, which is 10 times the general population risk. JScreen launched the PEACH BRCA Study, a telehealth-based platform for BRCA education and testing, with the goal of creating an effective model for BRCA testing in low-risk AJ individuals who do not meet national testing criteria. Other goals were to determine the rate of BRCA mutations in this group, to assess the adequacy of screening for the 3 common AJ founder mutations only, and to assess satisfaction with the telehealth model to help inform a national launch of a broader cancer genetic testing program. METHODS: Criteria for participation included those who were AJ, resided in the metro-Atlanta area, were aged 25 and older, and had no personal or close family history of BRCA-related cancers. Pre-test education was provided through a video and written summary, followed by complimentary BRCA1/2 sequencing and post-test genetic counseling. Participants responded to pre- and post-test surveys, which assessed knowledge and satisfaction. Those who were not eligible to participate were sent genetic counseling resources and later surveyed. RESULTS: Five hundred one participants were tested and the results included 4 positives (0.8% positivity rate), 494 negatives, and 3 variants of uncertain significance. Overall satisfaction with the study process was high (96.9/100), knowledge about BRCA was high (97.5% of participants passed a pre-test knowledge quiz), and satisfaction with pre- and post-test education was high (97.9% of participants were satisfied with the pre-test video and written summary, and 99.5% felt that their post-test genetic counseling session was valuable). Many participants expressed interest in receiving broader cancer testing. CONCLUSIONS: The BRCA founder mutation rate in a low-risk AJ population was significantly lower than the previously established AJ rate of 1 in 40. It was also determined that a telehealth model for a cancer genetics program is effective and acceptable to the population tested. This study established interest in broader cancer genetic testing through a telehealth platform and suggested that testing may be successful in the Jewish community at a national level and potentially in other populations, provided that patient education and genetic counseling are adequately incorporated.

Implementation of preventive and predictive BRCA testing in patients with breast, ovarian, pancreatic, and prostate cancer: a position paper of Italian Scientific Societies.

Constitutional BRCA1/BRCA2 pathogenic or likely pathogenic variants (PVs) are associated with an increased risk for developing breast and ovarian cancers. Current evidence indicates that BRCA1/2 PVs are also associated with pancreatic cancer, and that BRCA2 PVs are associated with prostate cancer risk. The identification of carriers of constitutional PVs in the BRCA1/2 genes allows the implementation of individual and family prevention pathways, through validated screening programs and risk-reducing strategies. According to the relevant and increasing therapeutic predictive implications, the inclusion of BRCA testing in the routine management of patients with breast, ovarian, pancreatic and prostate cancers represent a key requirement to optimize medical or surgical therapeutic and prevention decision-making, and access to specific anticancer therapies. Therefore, accurate patient selection, the use of standardized and harmonized procedures, and adherence to homogeneous testing criteria, are essential elements to implement BRCA testing in clinical practice. This consensus position paper has been developed and approved by a multidisciplinary Expert Panel of 64 professionals on behalf of the AIOM-AIRO-AISP-ANISC-AURO-Fondazione AIOM-SIAPEC/IAP-SIBioC-SICO-SIF-SIGE-SIGU-SIU-SIURO-UROP Italian Scientific Societies, and a patient association (aBRCAdaBRA Onlus). The working group included medical, surgical and radiation oncologists, medical and molecular geneticists, clinical molecular biologists, surgical and molecular pathologists, organ specialists such as gynecologists, gastroenterologists and urologists, and pharmacologists. The manuscript is based on the expert consensus and reports the best available evidence, according to the current eligibility criteria for BRCA testing and counseling, it also harmonizes with current Italian National Guidelines and Clinical Recommendations.

BRCA testing and testing results among women 18-65 years old.

Since the 1990 s discovery of BRCA1 and BRCA2 pathogenic variants in breast or ovarian cancer patients, genetic testing has been recommended as part of a targeted, individualized approach for cancer prevention and treatment in eligible individuals. The aim of this study was to assess trends in BRCA test rates and results among adult women aged 18 to 65 in the US between 2007 and 2017. Using Clinformatics© Data Mart (CDM) Electronic Health Records, we included 223,211 women 18-65 years old with documented BRCA testing results from 1/1/2007-9/30/2017. Positive results indicated the presence of pathogenic variantss. BRCA test rates increased significantly from 34 per 100,000 women in 2007 to 488 per 100,000 women in 2016 (APC 30.8, 95% confidence interval 26.6-35.1). Documented positive results decreased from 86.1% in 2007 to 78.0% in 2017(APC -0.6, 95% confidence interval -1.4-0.2). From 2007 to 2017, decreasing trends in the rates of documented positive results were observed among all three age groups (18-39, 40-54, and 55-65 years; largest in 40-54 group). In 2015-2017, women with positive test results were less likely to be non-Hispanic Whites, cancer patients, or living in the Northeast or an area with average household income ≥$50,000. Between 2007 and 2017, increasing use of BRCA testing for cancer prevention and treatment occurred, correlating to the observed decreasing documented positive test rate. The utilization of testing and corresponding test results differed significantly across races/ethnicities, suggestive of a divergent application of the same testing criteria.

Targeted BRCA1/2 population screening among Ashkenazi Jewish individuals using a web-enabled medical model: An observational cohort study.

PURPOSE: This study aimed to evaluate uptake and follow-up using internet-assisted population genetic testing (GT) for BRCA1/2 Ashkenazi Jewish founder pathogenic variants (AJPVs). METHODS: Across 4 cities in the United States, from December 2017 to March 2020, individuals aged ≥25 years with ≥1 Ashkenazi Jewish grandparent were offered enrollment. Participants consented and enrolled online with chatbot and video education, underwent BRCA1/2 AJPV GT, and chose to receive results from their primary care provider (PCP) or study staff. Surveys were conducted at baseline, at 12 weeks, and annually for 5 years. RESULTS: A total of 5193 participants enrolled and 4109 (79.1%) were tested (median age = 54, female = 77.1%). Upon enrollment, 35.1% of participants selected a PCP to disclose results, and 40.5% of PCPs agreed. Of those tested, 138 (3.4%) were AJPV heterozygotes of whom 21 (15.2%) had no significant family history of cancer, whereas 86 (62.3%) had a known familial pathogenic variant. At 12 weeks, 85.5% of participants with AJPVs planned increased cancer screening; only 3.7% with negative results and a significant family history reported further testing. CONCLUSION: Although continued follow-up is needed, internet-enabled outreach can expand access to targeted GT using a medical model. Observed challenges for population genetic screening efforts include recruitment barriers, improving PCP engagement, and increasing uptake of additional testing when indicated.

Tumor BRCA testing in ovarian cancer and EQA scheme: our experience of a critical evaluation.

Next generation sequencing (NGS) is a widespread molecular biology method integrated into clinical practice to detect genetic variants, for diagnostic and prognostic purposes. The scheduled external quality assessments (EQA) is integral part of clinical molecular laboratory quality assurance. The EQA provides an efficient system to compare analytic test performances among different laboratories, which is essential to evaluate consistency of molecular test. EQA failures demands targeted corrective action plans. In this context, the complexity of the NGS techniques requires careful and continuous quality control procedures. We report a tumor BRCA1/2 (tBRCA) testing benchmark discrepancy provided by the European Molecular Genetics Quality Network in our laboratory during a round of EQA for somatic mutation testing of BRCA genes in relation to ovarian cancer. The critical analysis emerging from the tBRCA EQA is presented. We underline that harmonization processes are still required for the EQA in the molecular biology field, especially if applied to the evaluation of methods characterized by high complexity.

Tumor BRCA testing can reveal a high tumor mutational burden related to POLE pathogenic variants.

OBJECTIVE: Tumors harboring a POLE pathogenic variant, associated with high tumor mutational burden, are good candidates for immunotherapy. However, POLE pathogenic variants are not currently screened in routine clinical practice. Can these tumors be identified by means of an already available test? METHODS: We describe seven tumors harboring a POLE pathogenic variant, among eight patients with tumors harboring multiple BRCA1/2 variants (from 4 to 20). All patients were managed at Institut Curie, Paris. Five patients were selected because of unexpected tumor BRCA testing results with multiple variants and another three patients were selected because of a POLE pathogenic variant detected by large tumor testing. We looked for other tumor variants by Next-Generation Sequencing in tumors harboring multiple BRCA1/2 variants, and for multiple BRCA1/2 variants in tumors harboring a POLE pathogenic variant. RESULTS: Four of the five tumors selected because of multiple BRCA1/2 variants exhibited a POLE pathogenic variant, and all three tumors selected for POLE pathogenic variants exhibited multiple BRCA1/2 variants. CONCLUSIONS: Tumor BRCA testing could be a way to detect tumors harboring a highly mutagenic POLE pathogenic variant.

Management of breast cancer patients with BRCA gene mutations in Lebanon of the Middle East: perspectives and challenges.

BACKGROUND: This commentary explores and discusses the challenges oncologists face in diagnosing and managing breast cancer patients with BRCA gene mutations in Lebanon and the Middle East. METHODS: Key opinion leaders shared their recommendations to achieve better patient outcomes and satisfaction based on evidence-based medicine and their clinical experience in BRCA management. RESULTS: Challenges associated with BRCA management can be divided into four main levels: physicians, patients, test, and treatment factors. More genetic counselors are to be identified given their important role in the management of individuals with BRCA gene mutations. CONCLUSION: Genetic counseling, continuing education, infrastructure, testing, expertise, and financial support are needed to fulfill the unmet needs in the management of BRCA mutation carriers.

The BRCA1 c.788G > T (NM_007294.4) variant in a high grade serous ovarian cancer (HGSOC) patient: foods for thought.

In this report we described the case of a BRCA1/2 (BRCA) molecular testing performed on tumor sample in a High Grade Serous Ovarian Cancer (HGSOC) patient with two different Next Generation Tumor Sequencing (NGTS) pipelines. The two clinical reports leaded to apparently different BRCA status, providing important foods for thought. After NGTS, the gene sequencing information (i.e., reads) are aligned to the reference gene sequences obtained from public databases, in order to provide an uniform nomenclature for unambiguous variant designation. However, the criteria adopted for variant reporting in tissue test are not always univocal. Particularly, this is the case of rare and unclassified BRCA variants for which the molecular evaluation may be a relevant challenge. Here we described a BRCA1 unclassified variant that may be re-evaluated in the context of alternative BRCA1 transcripts due to its different biological effect. We underlined that an in-depth knowledge of BRCA testing is mandatory for its appropriate use.

BRCA testing and outcomes in women with breast cancer.

MAIN PURPOSE: Germline BRCA mutations (BRCAm) strongly influence the risk of developing breast cancer. This study aimed to understand the role of BRCAm testing in affected individuals and to assess its impact on the outcome of BRCAm carriers compared to non-carriers (BRCAwt) with breast cancer. RESEARCH QUESTION: The research question is "Does standard of care testing for BRCAm improve survival outcomes of breast cancer patients?" METHODS: In a single institution observational cohort study, demographic and clinical characteristics were compared between breast cancer patients with and without BRCAm. Frequency of BRCA testing was assessed. Survival outcomes were assessed by initial treatment setting stratified by BRCA status. RESULTS: Of 5712 identified women with breast cancer, 14.6% (n = 835) were tested for a BRCA mutation and had a documented result. The total number and proportion of women tested for a BRCAm increased between 2000 and 2014, resulting in an increased number of BRCAm carriers identified. However, the proportion of women who underwent testing and had a BRCAm decreased during the study period from 27.5% in 2000-2004 to 13.3% in 2010-2014. Disease-free survival was similar in the adjuvant and neoadjuvant treatment settings between BRCAm and BRCAwt patients. Progression-free survival on first line treatment and overall survival for patients with metastatic disease was also similar between BRCAm and BRCAwt patients. CONCLUSIONS: The proportion of women tested and the number of BRCAm identified increased during the study period despite a decreasing proportion of positive results among women tested.

BRCA testing delay during the COVID-19 pandemic: How to act?

Recently, our lab, part of a referral center in Italy, reported its experience regarding the execution of germline BRCA1/2 (gBRCA) testing during the first months of the coronavirus disease-2019 (COVID-19) pandemic, which highlights a substantial reduction (about 60%) compared with the first 2 months of the current year. This evidence appeared to be a lockdown effect due to extraordinary restriction measures to slow down the spread of SARS-CoV-2. In this study, we aimed to evaluate the overall effects of the ongoing pandemic on gBRCA testing in our institution and to understand how COVID-19 has influenced testing after the complete lockdown (March 8-May 5, 2020). Additionally, we compared this year's trend with trends of the last 3 years to better monitor gBRCA testing progress. This detailed analysis highlights two important findings: (1) gBRCA testing did not increase significantly after the lockdown period (May-October 2020) compared with the lockdown period (March-April 2020), emphasizing that even after the lockdown period testing remained low. (2) Comparing the total tests per year (January-October 2017, 2018, 2019, with 2020), the impact of COVID-19 on gBRCA testing is apparent, with similarities of trends registered in 2017. These evidences reveal a gBRCA testing delay for cancer patients and healthy patients at this moment, and the new era of gBRCA testing in the management of ovarian, breast, pancreas and prostate cancer patients has been seriously questioned due to the COVID-19 pandemic. As consequence, we underline that measures to guarantee oncogenetic testing (e.g., gBRCA testing) along with new diagnostic/clinic strategies are mandatory. For these reasons, several proposals are presented in this study.

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

BACKGROUND: Testing 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. METHODS: We 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. RESULTS: Charts 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%). CONCLUSIONS: Adherence 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.

BRCA testing in a genomic diagnostics referral center during the COVID-19 pandemic.

The first person-to-person transmission of the 2019-novel coronavirus in Italy on 21 February 2020 led to an infection chain that represents one of the largest known COVID-19 outbreaks outside Asia. Hospitals have been forced to reorganized their units in response to prepare for an unforeseen healthcare emergency. In this context, our laboratory (Molecular and Genomic Diagnostics Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS) re-modulated its priorities by temporarily interrupting most of the molecular tests guaranteeing only those considered "urgent" and not postponable. In particular, this paper details changes regarding the execution of germline BRCA (gBRCA) testing in our laboratory. A substantial reduction in gBRCA testing (about 60%) compared to the first 2 months of the current year was registered, but the requests have not been reset. The requesting physicians were mainly gynaecologists and oncologists. These evidences further emphasize the new era of gBRCA testing in the management of cancer patients and confirms definitively the integration of gBRCA testing/Next Generation Sequencing (NGS) into clinical oncology. Finally, a re-organization of gBRCA testing in our Unit, mainly related to delayed and reduced arrival of tests was necessary, ensuring, however, a high-quality standard and reliability, mandatory for gBRCA testing in a clinical setting.

Recurrent Germline BRCA2 Gene Mutation in Lithuanian Family.

Approximately 10% of all breast cancer (BC) cases are familial and caused by inheritance of mutant BRCA1, BRCA2, or some other genes from the same DNA reparation pathway. Genetic counseling in families with cancer history is a powerful means for early cancer detection and active risk reduction through preventive interventions. This is the first report of the rare inherited BRCA2 frameshift-deletion mutation c.3847_3848delGT in one Lithuanian pedigree with the intense familial history of BC. Three BRCA2-positive blood relatives with BC of different biological types were identified in this pedigree with the same type mutation. All three cases were diagnosed with advanced stage ductal carcinoma. Markedly, polymorphic cells and numerous mitoses were identified in BC from the cases. Two patients from the family were diagnosed with the triple negative tumors, while one case had early onset of the hormone positive BC. Despite the variation in clinical and biological presentation of BC, all cases showed a good response to conventional treatment. In conclusion, the strong influence of BRCA2 mutation on the onset of BC of various biological types reveals the complexity of genetic counselling in families with BC history.