Referral for genetic counseling and testing in BRCA1/2 and Lynch syndromes: A nationwide study based on 240,134 consultations and 134,652 genetic tests.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1528-1528
Author(s):  
Pascal Pujol ◽  
Dominique Stoppa-Lyonnet ◽  
Thierry Frébourg ◽  
Julien Blin ◽  
Marie Christine Picot ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Lynch Syndrome ◽  
Cancer Genetics ◽  
Gene Mutations ◽  
Cancer Predisposition ◽  
Genetic Tests ◽  
Nationwide Study ◽  
Cancer Predisposition Syndrome ◽  
Mmr Genes ◽  
Standardized Parameters

1528 Background: Patients referral to dedicated consultations for cancer predisposition syndrome has become a standard in clinical practice. Based on nationwide data from the French national cancer institute (NCI), we analyzed the evolution of cancer genetics consultations and testing over time, and the uptake of targeted tests in relatives of families with a BRCA1/2 or MMR mutation. Methods: All French cancer genetics centres completed annually a survey collecting standardized parameters for the NCI from 2003 to 2011. We report on the analysis of a total of 240,134 consultations and 134,652 genetic tests that enabled to identify 32,494 mutation carriers. Results: From 2003 to 2011, 141,639 (59 %) and 55,698 (23.2 %) patients were referred for a breast or a colorectal cancer predisposition syndrome, respectively. During this period, we found a dramatic and steadily increase in genetic tests performed for the BRCA1/2 genes (from 2095 to 7393 tests/year, P<0.0001) but not for the MMR genes (from 1144 to 1635/year, P=NS). The percentage of deleterious mutations identified in the probands tested was 13.8 % and 20.9 % in BRCA1/2 and Lynch syndromes, respectively. In families with a BRCA1/2 or a MMR identified mutation, there was an average number of 3.03 relatives performing target tested. Conclusions: This nationwide study shows a lack of referral and genetic testing in Lynch syndrome as compared to BRCA1/2 syndrome. Only a third of relatives for a proband identified with a BRCA1/2 or MMR gene mutations performed a genetic targeted test. Enhanced information about validated benefit of genetic testing should be given to clinicians and patients particularly for Lynch syndrome and for relatives of a proband carrying an identified BRCA1/2 or MMR genes mutation.

Resource document for curriculum development in cancer genetics education. American Society of Clinical Oncology.

1997 ◽  
Vol 15 (5) ◽  
pp. 2157-2169 ◽  
Keyword(s):  
Genetic Testing ◽  
Clinical Oncology ◽  
Social Issues ◽  
Cancer Genetics ◽  
Cancer Predisposition ◽  
Genetics Education ◽  
Formal Instruction ◽  
Curriculum Guidelines ◽  
American Society

PURPOSE The rapid growth in the use of genetic testing for heritable cancers and other diseases has led to the establishment of many committees to assess the status and future implications of such testing. The American Society of Clinical Oncology (ASCO) published a statement on genetic testing for cancer susceptibility in May 1996. In that statement, ASCO recognized the need for a major initiative to develop courses and other educational materials for ASCO members and other health care professionals that were pertinent to cancer genetics and the role of cancer predisposition testing in clinical oncology. These curriculum guidelines represent an effort to promote formal instruction on the assessment and management of familial cancer risks in training programs and continuing education courses. DESIGN AND RESULTS An Ad hoc Task Force was created from the ASCO membership and other professional organizations. Goals of ASCO's cancer genetics education initiative, curriculum guidelines, and plans for implementation of the curriculum have been developed. To gain understanding and competency in cancer genetics and cancer predisposition testing, the curriculum emphasizes formal instruction in: (1) basic concepts and principles of genetics; (2) an understanding of the role of genetics in the etiology, diagnosis, and management of different malignancies; (3) an understanding of the ethical, legal, and social issues that surround predisposition testing; and (4) long-term management plans for individuals at high risk for cancer. This document is broad in scope and applicable to all types of malignancies. It should be considered as the framework around which cancer genetics education is developed. It is expected that implementation of training activities over the next few years will allow ASCO to fulfill its obligations to the membership. CONCLUSION This curriculum should prove a valuable guide to those who wish further education on cancer genetics and the appropriate use of cancer predisposition testing.

scholarly journals Factors Affecting Genetic Consultation in Adolescent and Young Adult Patients With Sarcoma

2021 ◽  
pp. 1-8
Author(s):  
Grace E. McKay ◽  
Anna L. Zakas ◽  
Fauzia Osman ◽  
Amanda Parkes
Keyword(s):  
Genetic Counseling ◽  
Genetic Testing ◽  
Young Adult ◽  
Chart Review ◽  
Univariate Analysis ◽  
Cancer Predisposition ◽  
Adolescent And Young Adult ◽  
Li Fraumeni Syndrome ◽  
Cancer Predisposition Syndrome ◽  
Genetic Consultation

Background: Given a link between sarcomas and hereditary cancer predisposition syndromes, including Li-Fraumeni syndrome, the consideration for genetic counseling is recommended for all adolescent and young adult (AYA) patients diagnosed with sarcoma. The aim of this study was to evaluate factors influencing genetic consultations in AYA patients with sarcoma at the University of Wisconsin (UW). Methods: A retrospective chart review was performed on AYA patients diagnosed with sarcoma between the ages of 15 and 39 years who were seen at least once between 2015 to 2019 at UW. Our chart review identified discussions regarding genetics, referrals to genetics, genetic consultations, and results of genetic testing. Variables hypothesized to affect patient referrals for genetic consultation were identified a priori. Descriptive statistical methods and a univariate analysis were used to identify patient characteristics associated with genetic counseling referral. Results: We identified 87 AYA patients with sarcoma. Only 19 (22%) of these patients had documentation of a discussion about genetics, 15 (17%) of whom were subsequently referred for genetic consultation. Of these 15 patients, 9 (60%) were seen in consultation. All 9 patients seen by genetics underwent genetic testing, with 4 (44%) of these patients having identified heritable cancer predisposition syndromes. Likelihood for genetics referral was linked most strongly to documented genetics discussion with an oncology provider (P<.001). Conclusions: Despite the recommendation for consideration for genetic counseling in AYA patients with sarcoma, <25% of such patients in our study had a documented discussion about genetics. Supporting this need, all referred patients met criteria for genetic testing, and 44% of tested patients were found to have a heritable cancer predisposition syndrome. These data support the initial conversation by a provider as critical to genetic referral and suggest the need for more specific national recommendations for the genetic evaluation of all AYA patients with sarcoma.

Molecular Diagnostics of Colorectal Cancer

2011 ◽  
Vol 135 (5) ◽  
pp. 578-587
Author(s):  
Ahmed Bedeir ◽  
Alyssa M. Krasinskas
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Microsatellite Instability ◽  
Molecular Diagnostics ◽  
Growth Factor Receptor ◽  
Gene Mutations ◽  
Response To Therapy ◽  
Molecular Testing ◽  
Cancer Predisposition Syndrome ◽  
Standard Tool

Abstract Context.—Of all gastrointestinal tract epithelial malignancies, molecular diagnostics has impacted colorectal cancer the most. Molecular testing can detect sporadic and inherited colorectal cancers that arise through the microsatellite instability pathway and can determine the efficacy of targeted drug therapy. Objectives.—To review the microsatellite instability pathway of colorectal carcinoma carcinogenesis and to demonstrate the diagnostic utility of molecular testing in the detection of patients with Lynch syndrome, an inherited disorder of this pathway. Also, to review the significance of detection of KRAS and BRAF gene mutations in predicting the response to anti–epidermal growth factor receptor therapies. Data Sources.—This article is based on original publications and review articles that are accessible through the PubMed biomedical database (US National Library of Medicine). Conclusions.—In modern pathology practice, molecular testing is a standard tool that is used to diagnose an inherited colorectal cancer predisposition syndrome (Lynch syndrome) and to help predict outcome and response to therapy for patients with advanced colorectal cancer.

What would the experts do? Genetic testing, surveillance, and risk-reduction preferences for BRCA and Lynch syndrome.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e12542-e12542
Author(s):  
Danielle C. Bonadies ◽  
Ellen T. Matloff ◽  
Karina L. Brierley ◽  
Anne Moyer
Keyword(s):  
Genetic Testing ◽  
Lynch Syndrome ◽  
Risk Reduction ◽  
Cancer Genetics ◽  
Uterine Cancer ◽  
Bilateral Mastectomy ◽  
National Society ◽  
National Guidelines ◽  
Online Questionnaire ◽  
Treatment Regimens

e12542 Background: Extensive data and national guidelines are now available regarding surveillance and risk reduction options for BRCA and Lynch syndrome mutation carriers. However, most of these options are presented as choices to patients who will often ask their providers, “What would you do?” We surveyed providers from multiple specialties to learn what they would do if at 50% risk to carry a BRCA or Lynch syndrome mutation. Methods: In July of 2012 we surveyed providers from multiple specialties via internet- based surveys. Participants were obtained through the American Medical Association and the National Society of Genetic Counselors. All responses were anonymized. Results: 1,313 specialists completed the online questionnaire. Those providers who commonly treat breast, ovarian, colon and uterine cancers were grouped and compared to providers who are less likely to be the treating specialist. We found statistically significant differences in the percentage of cancer genetics specialists who would pursue BRCA and Lynch syndrome testing compared with providers in other specialties (p=0.000, 0.007, respectively). We found statistically significant differences in the percentage of providers who treat breast or ovarian cancer that would opt for prophylactic bilateral mastectomy or prophylactic oophorectomy if BRCA+ (p=0.000, p=0.004, respectively) compared to other providers. We found statistically significant differences in the percentage of providers who treat colon or uterine cancer that would have their colon or uterus removed if found to carry a Lynch syndrome mutation (p=0.000, p=0.04, respectively) compared to other specialists. Conclusions: Providers’ specialties and, possibly, disease-specific exposure to surveillance and treatment regimens impacted their personal choices with respect to cancer genetic testing, surveillance and prophylactic surgeries for BRCA and Lynch syndrome.

scholarly journals Towards controlled terminology for reporting germline cancer susceptibility variants: an ENIGMA report

2019 ◽  
Vol 56 (6) ◽  
pp. 347-357 ◽  
Author(s):  
Amanda B Spurdle ◽  
Stephanie Greville-Heygate ◽  
Antonis C Antoniou ◽  
Melissa Brown ◽  
Leslie Burke ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Genetic Variants ◽  
Cancer Susceptibility ◽  
Cancer Genetics ◽  
Rapid Expansion ◽  
Monogenic Disease ◽  
Common Disease ◽  
Variant Interpretation ◽  
Genetic Tests ◽  
Cancer Susceptibility Genes

The vocabulary currently used to describe genetic variants and their consequences reflects many years of studying and discovering monogenic disease with high penetrance. With the recent rapid expansion of genetic testing brought about by wide availability of high-throughput massively parallel sequencing platforms, accurate variant interpretation has become a major issue. The vocabulary used to describe single genetic variants in silico, in vitro, in vivo and as a contributor to human disease uses terms in common, but the meaning is not necessarily shared across all these contexts. In the setting of cancer genetic tests, the added dimension of using data from genetic sequencing of tumour DNA to direct treatment is an additional source of confusion to those who are not experienced in cancer genetics. The language used to describe variants identified in cancer susceptibility genetic testing typically still reflects an outdated paradigm of Mendelian inheritance with dichotomous outcomes. Cancer is a common disease with complex genetic architecture; an improved lexicon is required to better communicate among scientists, clinicians and patients, the risks and implications of genetic variants detected. This review arises from a recognition of, and discussion about, inconsistencies in vocabulary usage by members of the ENIGMA international multidisciplinary consortium focused on variant classification in breast-ovarian cancer susceptibility genes. It sets out the vocabulary commonly used in genetic variant interpretation and reporting, and suggests a framework for a common vocabulary that may facilitate understanding and clarity in clinical reporting of germline genetic tests for cancer susceptibility.

scholarly journals Genetic testing for hereditary cancer predisposition: BRCA1/2, Lynch syndrome, and beyond

2016 ◽  
Vol 140 (3) ◽  
pp. 565-574 ◽  
Author(s):  
M.J. Hall ◽  
E.I. Obeid ◽  
S.C. Schwartz ◽  
G. Mantia-Smaldone ◽  
A.D. Forman ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Lynch Syndrome ◽  
Hereditary Cancer ◽  
Cancer Predisposition ◽  
Hereditary Cancer Predisposition

The importance of continued surveillance of high risk cancer families as illustrated in a family with Gardner’s syndrome

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1551-1551
Author(s):  
R. D. Legare ◽  
J. Scalia-Wilbur ◽  
J. Kent
Keyword(s):  
Genetic Testing ◽  
High Risk ◽  
Cancer Susceptibility ◽  
Cancer Genetics ◽  
Soft Tissue Tumors ◽  
Cancer Predisposition ◽  
Predisposition Genes ◽  
High Risk Cancer ◽  
Lost To Follow Up

1551 Background: The scientific community continues to rapidly discover cancer predisposition genes allowing high risk families to identify underlying genetic abnormalities providing more individualized medical management. Therefore, continued follow-up becomes critical and is exemplified by Family A, a case that had been lost to follow-up for almost 40 years. Family A was first reported in the literature in 1955 by Weiner and Cooper presenting with a dominant inheritance pattern of osteomatosis, multiple soft tissue tumors and colorectal adenomatosis polyposis consistent with several families previously reported by Gardner et al. between 1950–1953. The clinical diagnosis of Gardner syndrome was established. In 1969 Coli et al. further described the phenotypic manifestations of Family A’s second and third generations after which the family was largely lost to follow-up until two second generation members presented to our high-risk clinic. Methods: An updated family history was collected and compared to that previously reported in the literature. Results: An updated pedigree revealed new cases of breast, ovarian and primary peritioneal cancers in the second and third generations. A 39 year old woman diagnosed with a glioblastoma was also discovered. No family members had undergone genetic testing, however, analyses of the APC and BRCA genes are underway. Conclusions: The presence of multiple newly reported cases of breast and ovarian cancers within Family A raises concern for two independent cancer predisposition syndromes, Hereditary Breast and Ovarian Cancer Susceptibility syndrome (HBOCS) as well as Familial Adenomatous Polyposis (FAP). Though rarely gynecological tumors have been reported in FAP, this case emphasizes the need for practitioners to be aware of the potential presence of multiple hereditary cancer syndromes in one family. The dynamic changes in the pedigree of Family A underscore the importance of continued follow up for cancer families in which the underlying etiology is unknown. Such families should be followed in cancer genetics clinics to update family histories, ensure that appropriate screening regimens are followed, and to offer genetic testing if the appropriate analysis becomes available. No significant financial relationships to disclose.

Are immunohistochemical (IHC)/microsatellite instability (MSI) testing necessary as part of Lynch syndrome work-up in the era of multiplex genetic testing?

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 425-425
Author(s):  
Ahmad Fitri Idris ◽  
Simon D. Hooper ◽  
Michael P. Farrell ◽  
Carmel Nolan ◽  
Roisin Clarke ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Lynch Syndrome ◽  
Mismatch Repair ◽  
Median Time ◽  
Cancer Genetics ◽  
Positive Family History ◽  
Birth Date ◽  
Variants Of Uncertain Significance ◽  
Uncertain Significance ◽  
Work Up

425 Background: IHC for mismatch repair proteins and MSI are commonly used to direct genetic testing for Lynch Syndrome. Abnormal results in the setting of a positive family history often lead to genetic testing for Lynch syndrome. The often cumbersome process of completing IHC/MSI requires obtaining stored tissue +/- blood from a family member affected with cancer. Upfront genetic testing is not favoured due to concerns about identifying variants of uncertain significance. We performed a review of Lynch syndrome work-up in Ireland, and propose a model that is the reverse of the current international standard, and may expedite and simplify work up of these families. Methods: Data was ascertained from three cancer genetics services in Dublin and included the following variables: date of birth, date of request and reporting results for IHC, MSI and genetic tests. Time intervals were determined for LS work-up for all patients who had the process initiated in these 3 centres. Results: Probands from 50 families referred for LS work-up were included.The median time from date of IHC request to date of IHC report (total of 50 patients) was 4 weeks (range: 4 days to 36 weeks). The median time between date of IHC request to date of MSI report (n = 32 patients) was 20 weeks (range: 4 to 56 weeks). The median time from date of genetic test request to date of result (n = 9 patients) was 9 weeks (range: 2 to 26 weeks). The median time for completion of all 3 tests in one individual (n=3 patients) was 14 weeks (range: 10 to 60 weeks). Conclusions: The diagnostic pathway for Lynch syndrome is cumbersome and often lengthy. Appropriate upfront multiplex genetic testing would expedite the identification of mismatch repair gene mutation carriers. IHC/MSI testing could be used to characterise variants of uncertain significance.

Improved universal tumor screening program with paired testing: Experience at a large community-based teaching hospital.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e22505-e22505
Author(s):  
Gnyapti Majmudar ◽  
Kristina Ivan ◽  
Tara Rangarajan ◽  
Dana Zakalik
Keyword(s):  
Genetic Testing ◽  
Lynch Syndrome ◽  
Mismatch Repair ◽  
Teaching Hospital ◽  
Cancer Genetics ◽  
Screening Program ◽  
Braf V600e ◽  
Community Based ◽  
Large Community ◽  
Mmr Deficiency

e22505 Background: Lynch syndrome (LS) is the most common cause of hereditary predisposition to colon, endometrial, and other cancers. The universal tumor screening program for LS at Beaumont Health (BH) utilizes immunohistochemistry (IHC) of the mismatch repair (MMR) proteins to identify patients for genetics evaluation. We present the 8-year experience of the program at a large community-based teaching hospital. Methods: The MMR IHC results for all colorectal cancer (CRC) resection specimens screened from August 2012 to September 2020 were reviewed. Specimens with absent MLH1 and PMS2 were evaluated for MLH1 promoter hypermethylation with reflex to BRAF V600E mutation analysis. All abnormal results were referred for cancer genetics evaluation. The distribution of abnormal MMR and germline genetic testing results was analyzed. Results: Specimens from 2361 CRC resections were screened, and 511 specimens had abnormal MMR IHC (22%). Most cases of absent MLH1 and PMS2 were explained by hypermethylation or BRAF analysis (n = 338, 66% of all abnormal, 89% of MLH1 and PMS2). Of the remaining cases showing MMR deficiency (n = 173), the most common result was absence of MSH2 and MSH6 (n = 67), followed by absence of MLH1 and PMS2 (n=41, see table). Germline genetic testing of 83 individuals with abnormal MMR IHC revealed 49 cases of Lynch syndrome [MLH1 (n=9), MSH2 (n= 25), MSH6 (n=7), PMS2 (n=7), EPCAM (n=1)]. A significant proportion of cases (n=34, 40%) had negative germline testing, and had unexplained MMR deficiency. Paired germline/tumor testing was implemented in 2017, and 14 patients had this analysis. Using this approach, 5 individuals were identified to have somatic mutations explaining their result, and the proportion of unexplained cases was reduced to 29% (n = 4). Conclusions: Recent advances in cancer screening and therapeutics have underscored the importance of analyzing tumors for mismatch repair deficiency (dMMR), with known challenges to implementation and interpretation of results. The BH cancer genetics program has demonstrated successful growth of a universal tumor screening program over 8 years. This has led to the identification of a large number of dMMR tumors (22% of all CRC resections) and LS cases (2% of all CRC resections), which impacts management for patients and their families. Recent implementation of paired germline/tumor testing has improved the testing algorithm, and resulted in more accurate interpretation of a greater proportion of abnormal IHC results. This combined approach allows for focused high-risk screening for LS patients, access to novel therapeutic interventions including immune therapies for patients with dMMR tumors, and future precision oncology approaches.[Table: see text]

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