Genetic Cancer Risk Assessment Research Articles

Abstract 537: Information-driven approaches to predicting familial risk for prostate cancer

Abstract Given the known genetic heterogeneity of prostate cancer, risk assessment for this disease is a field that is likely to be positively impacted by improved interpretation of genetic variants identified through exome sequencing. At present, there is insufficient evidence to base decisions regarding screening, diagnosis and management of prostate cancer on genetic tests. While a few genes (such as BRCA2 and HOXB13) are definitively linked to prostate cancer risk, they are not found in sizeable patient populations. However, a growing number of candidates for prostate cancer risk have been proposed. As information resources including the TCGA and other consortium databases expand, clinicians and patients will face issues with how to interpret genetic data variant regarding cancer risk. The goal of the present work is to develop a paradigm that addresses the plausible scenario of a clinician seeking to provide prostate cancer genetic risk assessment for patients with personal and/or a family history of one or more types of cancer, but for whom access to relative specimens for sequencing analysis is highly limited. In particular, we focus on the development of an operational framework through which to select and evaluate germ-line variants which may contribute to familial cancer risk. Our study evaluates the current potential of integrated informatics resources to help identify clinically informative variants following exome sequencing of germ-line DNA from 12 prostate cancer patients with elevated risk of prostate or other cancers based on family history. We explored variants in genes meeting specific criteria: 1) genes thought to be relevant to hereditary prostate cancer, or experimentally validated as regulating the growth of prostate tumors in cell or animal models; 2) genes affected by somatic changes in cancer; 3) genes involved in DNA damage repair (DDR) including recently described androgen-regulated DDR genes; and 4) genes involved in disorders of glycosylation. We first filtered exome data based on the observed frequency of gene variants in the general population. We then utilized five independent in silico predictors and expert analysis of protein structure and interactions to identify function-disrupting rare variants. We described an average of 4 potentially disruptive variants in each individual and annotated them in the context of the human variation data accumulated over the last few years and represented in various public databases. Novel variants were found in PALB2, RAD54L2, HSD3B1, NRIP1, SCN11A, CYPBP1, SULT1E1 and UBE2D3. Molecular modeling of a p.(S221N) mutation in the steroid binding site of the aldo-keto reductase AKR1C1 showed it would be predicted to disrupt the active site, influencing androgen metabolism. Our study highlights the need and potential for well-curated databases of variants with clinical relevance that will ultimately facilitate germ-line exome testing in the clinical setting. Citation Format: Emmanuelle Nicolas, Yan Zhou, Ilya G. Serebriiskii, Mark D. Andrake, Elizabeth A. Handorf, Roland L. Dunbrack, Veda N. Giri, Eric A. Ross, Erica A. Golemis, Michael J. Hall, Mary B. Daly. Information-driven approaches to predicting familial risk for prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 537. doi:10.1158/1538-7445.AM2015-537

Abstract P1-11-04: Implementation of cancer risk assessment and genetic testing in underserved patients

Abstract PURPOSE: There is great disparity in genetic testing for breast cancer. Hispanic/Latina women with breast cancer are more likely to have adverse clinical features and have a high prevalence of BRCA mutations. We propose that Academic-Community clinic partnerships offer great potential to provide access to genetic cancer risk assessment (GCRA) for underserved communities, including Hispanic/Latina women. The study also evaluated the willingness of these patients to participate in biospecimen collection. METHODS: This study assessed the implementation of a limited GRCA and testing service at a safety net institution from July 1, 2011 to December 31, 2013. In the 10 years prior, only two breast cancer patients had undergone genetic testing and both were insured. The inability to perform GCRA was recognized as a critical area of need. Therefore, a breast surgical oncologist received training with City of Hope National Medical Center. The goal is to provide clinicians the appropriate skills to provide GCRA services in areas where these are not available. Three generation pedigrees and sociodemographic information were collected including health literacy, education, self-reported income, employment status, and insurance status. We conducted a comparison of the patient characteristics along the continuum of GCRA, genetic testing, and mutation carriers, and for the latter group, we describe the BRCA mutation profile. RESULTS: 125 patients were offered GCRA and all accepted, of which 70% of this patient population was Hispanic and 66% did not have health insurance. Of the 125 patients, 84 (67%) were recommended to undergo genetic testing and 81 (96%) agreed. Of the 81 patients who underwent genetic testing, 68 were also asked to participate in the City of Hope Cancer Screening and Prevention registry and all but one (94%) agreed. Significant differences between patients who had genetic testing and those who did not were shown for race/ethnicity, insurance, and family history. A higher percentage of Hispanic patients and patients with no insurance underwent testing. Additional trends in differences between patients who were tested vs. those who were not were observed for education and health literacy but these were not statistically significant. Few differences were observed between women who had genetic testing and mutation carriers; however, the number of carriers was too small to merit statistical testing. Twelve of 81 (15%) patients were found to have deleterious mutations, seven BRCA 1 and five BRCA 2. Of the 12 mutation carriers, one patient had ovarian cancer and therefore had already undergone bilateral salpingo-oophorectomy and two others underwent RRSO. Six are either considering RRSO or getting financial assistance for the operation. The last three are still undergoing breast cancer treatment. CONCLUSION: Results of our experience at a safety net hospital with a largely minority and uninsured population show that limited GCRA and testing can be successfully implemented. The great majority of patients agree to undergo counseling, testing, and participate in biospecimen research registries. Current recommendations for genetic counseling are far from being met across the country and this model could be considered for similar safety net populations. Citation Format: Ian K Komenaka, Lisa M Winton, Jesse N Nodora, Lisa Madlensky, Meredith A Heberer, Richard Schwab, Marcia E Bouton, Jeffrey N Weitzel, Maria Elena Martinez. Implementation of cancer risk assessment and genetic testing in underserved patients [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-11-04.

Genetic risk assessment for breast and gynecological malignancies.

Breast cancer and gynecological cancers impact a significant portion of women each year. Identifying women at high risk is essential for implementation of screening and risk reduction recommendations. Risk assessment for these cancers involves an evaluation of many factors. This review discusses an overview of hereditary breast and gynecological cancers and the process of a cancer genetic risk assessment. Risk assessment models for breast cancer should be used with caution, especially in populations in which they are not validated. Additionally, the BRCAPRO model may underestimate the likelihood of BRCA mutations in certain populations.The utilization of next-generation sequencing panels is increasing. Benefits and limitations of panel testing are described in the literature. There are currently no guidelines for the use of panel testing; however, some reports of institutional experiences and recommendations are available. Cancer genetic risk assessment is complex, and models developed to estimate risk may not apply to all populations. Identifying genetic factors related to cancer risk is also becoming increasingly complex with the clinical implementation of panel testing. This testing approach should be critically evaluated by healthcare providers. Further research is needed to create evidence-based guidelines for panel testing and management recommendations for moderately penetrant genes.

Referral of Ovarian Cancer Patients for Genetic Counselling by Oncologists: Need for Improvement

Background/Aims: Nearly 15% of all ovarian cancer patients carry a germline BRCA mutation. A pilot project was started at IRCCS AOU San Martino - IST, Genoa, to assess the feasibility and consequences of offering genetic counselling to all ovarian cancer patients during routine oncology appointments. We present early results of this project. Methods: Patients who attended an oncology visit at the Medical Oncology Unit 1 between November 2012 and December 2013 were identified. Medical records were reviewed for clinical data, genetic counselling and testing outcomes. Results: Out of 104 women diagnosed with ovarian cancer undergoing an oncology visit, 94 had not had genetic counselling in the past. Twenty-nine patients (29/94, 31%) were referred to the Unit of Hereditary Cancer; of these, 14/26 (54%) were referred at the first visit and 15/68 (22%) at the follow-up visit (p = 0.003). Most referred women attended genetic counselling (22/29, 76%) and had BRCA genetic testing (21/22, 95%). Four BRCA1 mutations were detected (4/21, 19%). Conclusions: Oncologists discuss genetic counselling with a minority of ovarian cancer patients. Mainstreaming such practice is important to optimize the management of these patients and their families. Efforts are needed to identify new models for introducing ovarian cancer genetic risk assessment in oncology practice.

Identifying hereditary cancer: Genetic counseling and cancer risk assessment

The goal of cancer genetic counseling, risk assessment, and testing is to identify individuals and families at risk for hereditary cancer, such that targeted management strategies can be used to reduce associated morbidity and mortality. Involvement of a qualified cancer genetic service provider helps to ensure that at-risk individuals identified and offered appropriate education, risk assessment, genetic testing, and follow-up risk management strategies. There are multiple screening and hereditary risk models available to help the clinician identify who needs to be referred to cancer genetic counseling and to facilitate the cancer risk assessment process. Genetic testing should only be pursued with fully informed consent in the context of pretest counseling to ensure that the individual understands the benefits, risks, and limitations of genetic testing, possible results, and their implications. Incorporating psychosocial assessment throughout the counseling session may assist the individual in their understanding of genetic testing in the context of their support resources and coping mechanisms and may help with decision making. There is a growing public awareness of and interest in cancer genetic testing, as well as increasing complexity of available testing options and results. It is therefore essential that cancer genetic professionals, primary care providers, and oncology practitioners work together to ensure that genetic testing for hereditary cancer syndromes is used in the most appropriate and effective way.

Improving referral for genetic risk assessment in ovarian cancer using an electronic medical record system.

We sought to evaluate an electronic referral form to increase referral for genetic risk assessment of women with newly diagnosed epithelial ovarian cancer. A form summarizing referral for genetic counseling for women with ovarian cancer was introduced into the electronic medical record allowing gynecologic oncologists to electronically submit a request for genetic services. Analysis compared patient and provider characteristics for women newly diagnosed with ovarian, fallopian tube, and primary peritoneal cancer referred 1 year before and after introducing the form. All patients were seen in a single fee-for-service university-based cancer center clinic. There were 86 newly diagnosed ovarian cancer patients seen before and 83 seen after the introduction of the electronic referral form. Most lived in the metropolitan area and had stage III to IV disease, serous histology, a documented family history, and a treating oncologist who was less than 10 years from completion of fellowship. Postintervention referral rates increased from 17% to 30% (P = 0.053). Factors best predicting referral were whether the patient was seen after the intervention (P = 0.009), resided in the metropolitan area (P = 0.006), and had been identified as at high hereditary risk (P < 0.0001). Sixty percent of the referred patients participated in counseling. There were no differences in baseline characteristics of the referred patients before and after the intervention. Referral rates increased with the introduction of an electronic medical record referral form suggesting that streamlining the physician referral process might be effective at increasing referrals for cancer genetic risk assessment.

Abstract P2-18-16: Patients’ impression of the expected appearance of breasts in 2013

Abstract Background: Concern exists about the increasing rate of bilateral mastectomy for patients with unilateral breast cancer. Patient concern for second primary, use of breast MRI, and increased genetic cancer risk assessment all may influence choice of operation. In recent years, cosmetic breast augmentation has also become more common. This study was performed to evaluate women's perception of the current expected appearance of breasts. Methods: From April 2012 to May 2013, all patients seen at a Breast Clinic were shown two pictures (A “natural” and B “augmented”) and asked “What is the expected appearance of breasts in 2012(2013)?” Sociodemographic, clinical, and treatment variables were collected. Univariate analysis was performed to identify variables which were associated with picture choice. All of the variables with a p-value &amp;lt;0.10 were included in the multivariate analysis. Results: 1,177 consecutive patients were seen with mean age 45 years. 93% of the patients were insured with Medicaid or uninsured and 19% were non-Hispanic White (NHW). The mean monthly income was only $1104. Overall 70% of patients felt that the augmented appearance is “expected in 2013.” Age was strongly associated with augmented appearance as younger patients were significantly more likely to choose picture B: age less than 40 years (85%), age 40-49 years (67%), age 50-59 years (65%), and age 60+ years (51%). Patients of all race/ethnic groups felt that the augmented appearance was expected. NHW 65%, AA 67%, and Hispanic 71%. Multivariate analysis found that more years of education (p = 0.001), younger age and lower BMI were strongly associated (p &amp;lt; 0.0001) with choosing the augmented appearance as “expected in 2013.” Of the 1177 patients, 337 breast cancer patients were seen. Overall 62% felt that the augmented appearance was expected. Of those who underwent an operation, 178 (58%) patients underwent breast conservation and 62% felt the augmented appearance was expected. Of 128 patients who underwent mastectomy, 36 (28%) underwent reconstruction. 23 patients underwent bilateral mastectomy. Of those who underwent mastectomy alone (41/83 = 49%) only about half felt the augmented appearance was expected. By contrast those who underwent reconstruction (33/36 = 92%; p &amp;lt; 0.001) or bilateral mastectomy (17/23 = 74%; p = 0.057), were significantly more likely than those who underwent mastectomy alone to feel the augmented appearance was expected. Conclusions: The current study suggests women's perception of the expected appearance of breasts is changing. Younger age was strongly associated with the perception that the “augmented” appearance is expected. This change may affect patients’ choice in surgical operations with more mastectomies and reconstructions in the future. In October 2012 from a common women's periodical, when asked about her choice of operation for a small area of unilateral DCIS, one woman responded, “Just take them off and give me implants. Everybody has implants; it's no big deal.” Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-18-16.

Abstract P3-07-06: BRCA mutations among Hispanic breast cancer patients of Mexican origin in El Paso, TX

Abstract Introduction: El Paso, TX is a large American-Mexican border city of population around 900,000, 85% Hispanic of Mexican origin. Limited cancer research has been conducted in this population. The relative homogeneity of this Hispanic population lends a unique opportunity to study the prevalence of BRCA mutations among Hispanic patients of Mexican origin, to identify reported Mexican founder or recurrent mutations, and to study the breast cancer characteristics in mutation carriers. Methods: Hispanic women with a personal history of breast cancer, who presented consecutively for genetic cancer risk assessment, were enrolled in an Institutional Review Board -approved registry and underwent BRCA testing bases on NCCN guidelines. The characteristics of tumors and patients with positive BRCA mutation were analyzed. Descriptive statistics were utilized. Results: 59 patients were screened; 13 patients (22%) tested positive. Mean age was 50 years; 8 patients (62%) had stages I or II, 2 patients stage III, and 3 unknown. 10 (77%) ductal, 1 (7%) lobular and 2 undetermined; 30% had ER positive tumors versus 61% ER negative; 69% had HER2 -neu negative tumors and 23% HER2-neu positive; 62% were triple negative. Nine patients (69%) were diagnosed with breast cancer at younger than 50 years. Median BMI was 31.78. Ten patients had BRCA1 mutations and 3 BRCA2 mutations. A total of 9 unique deleterious BRCA Mutations were observed, BRCA1 R71G (330A&amp;gt;G);del exons 1-2;C1787S(5478T&amp;gt;A) and G1788D(5482 G&amp;gt;A); C1225X (3794 C&amp;gt;A); A 1708E(5242 C&amp;gt;A); R1751X(5370C&amp;gt;T; and del exons 9-12 and BRCA2 Q742X (2452 C&amp;gt;T); and 3492 insT Conclusion: This study confirms that breast cancer patients with BRCA mutations in the El Paso, TX present at a younger age, and have predominantly triple negative tumors. Of particular interest is 44% (4 of 9) BRCA mutations (BRCA1 exon 9-12 del; C1787S &amp; G1788D and BRCA 2 3492insT; Q742X) identified have been reported as recurrent mutations in Hispanic individuals from Mexico as the country of origin, including BRCA1 ex9-12del, the 1st Mexican founder mutation and 100% of the BRCA2 mutations. A more cost-effective approach to initial screening of Hispanic individuals based on country of origin may be desirable and would potentially decrease the number of cases requiring complete sequencing. Increasing breast cancer awareness and encouraging genetic counseling among high risk younger patients of Mexican descent is also needed. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-07-06.

Models of Service Delivery for Cancer Genetic Risk Assessment and Counseling

Increasing awareness of and the potentially concomitant increasing demand for cancer genetic services is driving the need to explore more efficient models of service delivery. The aims of this study were to determine which service delivery models are most commonly used by genetic counselors, assess how often they are used, compare the efficiency of each model as well as impact on access to services, and investigate the perceived benefits and barriers of each. Full members of the NSGC Familial Cancer Special Interest Group who subscribe to its listserv were invited to participate in a web-based survey. Eligible respondents were asked which of ten defined service delivery models they use and specific questions related to aspects of model use. One-hundred ninety-two of the approximately 450 members of the listserv responded (42.7%); 177 (92.2%) had provided clinical service in the last year and were eligible to complete all sections of the survey. The four direct care models most commonly used were the (traditional) face-to-face pre- and post-test model (92.2%), the face-to-face pretest without face-to-face post-test model (86.5%), the post-test counseling only for complex results model (36.2%), and the post test counseling for all results model (18.3%). Those using the face-to-face pretest only, post-test all, and post-test complex models reported seeing more new patients than when they used the traditional model and these differences were statistically significantly. There were no significant differences in appointment wait times or distances traveled by patients when comparing use of the traditional model to the other three models. Respondents recognize that a benefit of using alternative service delivery models is increased access to services; however, some are concerned that this may affect quality of care.

Could Triaging Family History of Cancer during Palliative Care Enable Earlier Genetic Counseling Intervention?

Patients are commonly referred to cancer genetics services when all affected family members are deceased. This makes genetic testing and risk assessment more difficult, reducing the benefit from screening and prophylactic treatment. Observational, retrospective, cohort study of 508 randomly selected patients referred to a regional cancer genetics unit, using review of case notes to explore whether a simple clinical "3, 2, 1" family history rule could have been used to improve timely and appropriate referrals for genetic assessment. The 3, 2, 1 criteria are: three affected relatives with the same/associated cancers, across two generations, with at least one person affected age <50 years. Most (71% [362]) genetic risk assessment referrals were in unaffected individuals and 22% (80) of these were referred after all affected family members had died, including 24% (19) who lost their last remaining affected relative in the previous year. Most (59% [301]) referrals met all 3, 2, 1 criteria, and 67% of these could have been made earlier in clinical practice. A further 23% (115) met two of the three criteria. Using a simple "3, 2, 1" family rule in cancer care and particularly in palliative care could enable earlier cancer genetic risk assessment for unaffected relatives, improving the potential to benefit from targeted screening and intervention.

Resource and quality information provided by compliance with NCCN hereditary breast cancer guidelines.

5 Background: NCCN provides guidelines for breast cancer genetic risk assessment and testing. Measuring compliance with NCCN Guidelines (NG) can identify quality gaps. Methods: After IRB approval, a retrospective review of a prospective database of breast cancer patients was conducted to measure compliance with NG for genetic counseling and BRCA testing. Entry criteria were breast cancer patients with diagnosis and treatment at our center, during the 3 year period ending 12/31/11. Genetic counselors (GC) used NG and BRCAPRO modeling in all patients. Surgeon and GC pedigree analyses were compared. Results: Surgeons constructed pedigrees in 675 breast cancer patients and referred 42% (286/675) to the GC. The decision to refer was NCCN compliant in 671/675 (99%). The GC corrected the pedigree in 14% (39/286); nearly all due to the GC identifying extra breast or ovarian cancers. The mean BRCAPRO probability in referred patients was 7.2%. Fifty-nine percent (170/286) of patients seen by the GC received a recommendation for BRCA testing. The NG compliance rate for testing was 98% (170/174). Of 174 BRCA tests offered to patients, 74% (128/174) underwent testing. In tested patients, there were 4% BRCA1+, 5% BRCA 2+, and 1% uncertain variants. Total patient charges for 128 tests were $696,000 ($4,000/test). If the threshold for testing was BRCAPRO &gt; 5% or &gt;10%, then 69 ($276,000) and 45 ($180,000) (p&lt;0.001) patient charges would have occurred, and no patient with BRCA + status would have been missed. Conclusions: High rates of NCCN guideline compliance for genetic counseling and testing are achievable. Our GC's improve accuracy of pedigree assessment and demonstrate adherence to NCCN guidelines, resulting in more testing compared to BRCAPRO modeling. The balance between different methods to trigger testing, their sensitivity, and cost deserves more study, but the observational data contained herein provides information for provider and payer stakeholders regarding estimated GC resources and cost of care.

The Need to Build Trust: A Perspective on Disparities in Genetic Testing

Genetic Testing and Molecular BiomarkersVol. 17, No. 9 PerspectiveThe Need to Build Trust: A Perspective on Disparities in Genetic TestingKalyn Saulsberry and Sharon F. TerryKalyn SaulsberryHarvard College, Cambridge, Massachusetts.Genetic Alliance, Washington, District of Columbia.Search for more papers by this author and Sharon F. TerryGenetic Alliance, Washington, District of Columbia.Search for more papers by this authorPublished Online:3 Sep 2013https://doi.org/10.1089/gtmb.2013.1548AboutSectionsView articleView Full TextPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"The Need to Build Trust: A Perspective on Disparities in Genetic Testing." , 17(9), pp. 647–648FiguresReferencesRelatedDetailsCited byBeliefs and willingness towards participating in genetic testing for depression in low-income and racial/ethnic minority mothers at-riskArchives of Psychiatric Nursing, Vol. 41Disparities in cancer genetics care by race/ethnicity among pan‐cancer patients with pathogenic germline variants30 August 2022 | Cancer, Vol. 128, No. 21Whole-exome Sequencing of Nigerian Prostate Tumors from the Prostate Cancer Transatlantic Consortium (CaPTC) Reveals DNA Repair Genes Associated with African AncestryCancer Research Communications, Vol. 2, No. 9Disparities in germline testing among racial minorities with prostate cancer13 November 2021 | Prostate Cancer and Prostatic Diseases, Vol. 25, No. 3Germline alterations among Hispanic men with prostate cancer28 February 2022 | Prostate Cancer and Prostatic Diseases, Vol. 25, No. 3Impact of Health Perception and Knowledge on Genetic Testing Decisions Using the Health Belief ModelJCO Clinical Cancer Informatics, Vol. 101, No. 6Knowledge and perceptions of the genetic counseling profession among a national cross‐sectional sample of U.S. adults20 July 2021 | Journal of Genetic Counseling, Vol. 31, No. 1Disparities in Genetic Testing for Heritable Solid-Tumor MalignanciesSurgical Oncology Clinics of North America, Vol. 31, No. 1Operationalizing Genetic Testing in the Care of Patients with Prostate Cancer28 January 2022“It didn’t mean anything” – moving within a landscape of knowledge to interpret genetics and genetic test results within familial cancer concerns1 December 2021 | New Genetics and Society, Vol. 40, No. 4Pursuing genetic testing for children with autism spectrum disorders: What do parents think?28 September 2020 | Journal of Genetic Counseling, Vol. 30, No. 2Use of Diagnostic Testing and Intervention for Sensorineural Hearing Loss in US Children From 2008 to 2018JAMA Otolaryngology–Head & Neck Surgery, Vol. 147, No. 3Massively Parallel Sequencing for Rare Genetic Disorders: Potential and Pitfalls19 February 2021 | Frontiers in Endocrinology, Vol. 11Uncovering social structures and informational prejudices to reduce inequity in delivery and uptake of new molecular technologies7 January 2020 | Journal of Medical Ethics, Vol. 46, No. 11Ethnic disparities among men with prostate cancer undergoing germline testingUrologic Oncology: Seminars and Original Investigations, Vol. 38, No. 3Inclusion of Indigenous Australians in biobanks: a step to reducing inequity in health care3 June 2019 | Medical Journal of Australia, Vol. 211, No. 1The Changing Role of the Genetic Counsellor in the Genomics Era2 May 2019 | Current Genetic Medicine Reports, Vol. 7, No. 2Black and Minority Ethnic women's decision-making for risk reduction strategies after BRCA testing: Use of context and knowledgeEuropean Journal of Medical Genetics, Vol. 62, No. 5Privacy and ethical challenges in next-generation sequencing8 April 2019 | Expert Review of Precision Medicine and Drug Development, Vol. 4, No. 2Precision Medicine: Familiarity, Perceived Health Drivers, and Genetic Testing Considerations Across Health Literacy Levels in a Diverse Sample14 December 2018 | Journal of Genetic Counseling, Vol. 28, No. 1Physician Communication of Genomic Results in a Diagnostic Odyssey Case Series1 January 2019 | Pediatrics, Vol. 143, No. Supplement_1Towards Cultural Competence in the Genomic Age: a Review of Current Health Care Provider Educational Trainings and Interventions26 September 2018 | Current Genetic Medicine Reports, Vol. 6, No. 4Impacts of variants of uncertain significance on parental perceptions of children after prenatal chromosome microarray testing24 July 2018 | Prenatal Diagnosis, Vol. 38, No. 10Genetic counseling among minority populations in the era of precision medicine25 March 2018 | American Journal of Medical Genetics Part C: Seminars in Medical Genetics, Vol. 178, No. 1The Spectrum of Caregiving in Palliative Care for Serious, Advanced, Rare Diseases: Key Issues and Research Directions23 June 2016 | Journal of Palliative Medicine, Vol. 19, No. 7Disparities in Cancer Genetic Risk Assessment and Testing1 July 2016 | Oncology Nursing Forum, Vol. 43, No. 4 Volume 17Issue 9Sep 2013 InformationCopyright 2013, Mary Ann Liebert, Inc.To cite this article:Kalyn Saulsberry and Sharon F. Terry.The Need to Build Trust: A Perspective on Disparities in Genetic Testing.Genetic Testing and Molecular Biomarkers.Sep 2013.647-648.http://doi.org/10.1089/gtmb.2013.1548Published in Volume: 17 Issue 9: September 3, 2013PDF download

BRCA sequencing and large rearrangement testing in young Black women with breast cancer

Young Black women in the United States are disproportionately afflicted with breast cancer, a proportion of which may be due to BRCA1 and BRCA2 (BRCA) gene mutations. In a cancer registry-based sample of young Black women with breast cancer, we evaluated: (1) the prevalence of BRCA mutations detected through full gene sequencing and large rearrangements testing and (2) proportions that accessed genetic services pre-dating study enrollment. Black women diagnosed with invasive breast cancer ≤age 50years in 2009-2012 were recruited through the Florida Cancer Registry. Participants completed genetic counseling, a study questionnaire, and consent for medical record release. Saliva specimens were collected for BRCA testing. Overall, 13 participants (9%) had BRCA mutations detected (including 11 through full gene sequencing and two through large rearrangements testing). One of these large rearrangements, BRCA1 (delExon8), was identified in a participant who had previously tested negative on clinical comprehensive BRCAnalysis that was performed prior to undergoing a lumpectomy. Although all 144 participants met national criteria for referral for cancer genetic risk assessment, 61 (42%) were referred for genetic counseling and/or had genetic testing preceding study enrollment, and only 20 (14%) received genetic counseling. Our findings emphasize the importance of large rearrangements testing to increase detection of deleterious BRCA mutations in young Black women with breast cancer. The registry-based design of our study increase the generalizability of findings compared with efforts focused on clinic-based populations. Furthermore, results suggest efforts are needed to improve access to genetic counseling and testing.

Next-generation sequencing for genetic cancer risk assessment: Critical needs and perceptions of community clinicians.

1536 Background: Current standard-of-care practice for genetic cancer risk assessment (GCRA) focuses on single-gene testing for specific hereditary cancer syndromes. Next-generation sequencing (NGS) technologies recently became available for clinical applications. This study explored the perspectives and experiences of community-based clinicians regarding NGS testing for personalized GCRA. Methods: A 27-item survey was developed and administered online to 325 members of an interdisciplinary nationwide clinical cancer genetics community of practice. Results: Of 94 (29%) respondents, 25 (27%) have ordered at least one multi-gene panel and only 2 (2.1%) have ordered a whole exome or genome test from a commercial vendor for GCRA. Concerns about clinical utility, the challenge of interpreting and communicating results, lack of knowledge about and potential costs were most often cited as reasons for not pursuing NGS testing. Respondents were significantly more confident about their ability to interpret and counsel about single gene test results compared with multi-gene panels or whole exome/genome sequencing; and about multi-gene panels over whole exome/genome sequencing (p&lt;.0001 for all comparisons). Conclusions: Findings suggest that while NGS tests are entering the realm of GCRA, multidisciplinary genomics education and clinical support resources are needed to address barriers to utilization and promote successful integration of NGS testing into community-based GCRA practice settings.

Resource and quality information provided by compliance with NCCN hereditary breast cancer guidelines.

e17583 Background: NCCN provides guidelines for breast cancer genetic risk assessment and testing. Measuring compliance with NCCN Guidelines (NG) can identify quality gaps. Methods: After IRB approval, a retrospective review of a prospective database of breast cancer patients was conducted to measure compliance with NG for genetic counseling and BRCA testing. Entry criteria were breast cancer patients with diagnosis and treatment at our center, during the 3 year period ending 12/31/11. Genetic counselors (GC) used NG and BRCAPRO modeling in all patients. Surgeon and GC pedigree analyses were compared. A change to the history was significant if the GC identified information that led to increased or decreased cases of breast or ovarian ca. Results: Surgeons constructed pedigrees in 675 breast cancer patients and referred 42% (286/675) to the GC. The decision to refer was NCCN compliant in 671/675 (99%). The GC corrected the pedigree in 14% (39/286); nearly all due to the GC identifying extra breast or ovarian cancers. The mean BRCAPRO probability in referred patients was 7.2%. Fifty-nine percent (170/286) of patients seen by the GC received a recommendation for BRCA testing. The NG compliance rate for testing was 98% (170/174). Of 174 BRCA tests offered to patients, 74% (128/174) underwent testing. In tested patients, there were 4% BRCA1+, 5% BRCA 2+, and 1% uncertain variants. Total patient charges for 128 tests were $696,000 ($4000/test). If the threshold for testing was BRCAPRO &gt; 5% or &gt;10%, then 69 ($276,000) and 45($180,000) (p&lt;0.001) patient charges would have occurred, and no patient with BRCA + status would have been missed. Conclusions: High rates of NCCN guideline compliance for genetic counseling and testing are achievable. Our GC's improve accuracy of pedigree assessment and demonstrate adherence to NCCN guidelines, resulting in more testing compared to BRCAPRO modeling. The balance between different methods to trigger testing, their sensitivity, and cost deserves more study, but the observational data contained herein provides information for provider and payer stakeholders regarding estimated GC resources and cost of care.

A cluster-randomised, parallel group, controlled intervention study of genetic prostate cancer risk assessment and use of PSA tests in general practice—the ProCaRis study: study protocol

IntroductionUnsystematic screening for prostate cancer (PCa) is common, causing a high number of false-positive results. Valid instruments for assessment of individual risk of PCa have been called for. A DNA-based...

Prevalence and Type ofBRCAMutations in Hispanics Undergoing Genetic Cancer Risk Assessment in the Southwestern United States: A Report From the Clinical Cancer Genetics Community Research Network

To determine the prevalence and type of BRCA1 and BRCA2 (BRCA) mutations among Hispanics in the Southwestern United States and their potential impact on genetic cancer risk assessment (GCRA). Hispanics (n = 746) with a personal or family history of breast and/or ovarian cancer were enrolled in an institutional review board-approved registry and received GCRA and BRCA testing within a consortium of 14 clinics. Population-based Hispanic breast cancer cases (n = 492) enrolled in the Northern California Breast Cancer Family Registry, negative by sequencing for BRCA mutations, were analyzed for the presence of the BRCA1 ex9-12del large rearrangement. Deleterious BRCA mutations were detected in 189 (25%) of 746 familial clinic patients (124 BRCA1, 65 BRCA2); 21 (11%) of 189 were large rearrangement mutations, of which 62% (13 of 21) were BRCA1 ex9-12del. Nine recurrent mutations accounted for 53% of the total. Among these, BRCA1 ex9-12del seems to be a Mexican founder mutation and represents 10% to 12% of all BRCA1 mutations in clinic- and population-based cohorts in the United States. BRCA mutations were prevalent in the largest study of Hispanic breast and/or ovarian cancer families in the United States to date, and a significant proportion were large rearrangement mutations. The high frequency of large rearrangement mutations warrants screening in every case. We document the first Mexican founder mutation (BRCA1 ex9-12del), which, along with other recurrent mutations, suggests the potential for a cost-effective panel approach to ancestry-informed GCRA.

NSGC Practice Guideline: Risk Assessment and Genetic Counseling for Hereditary Breast and Ovarian Cancer

The purpose of this document is to present a current and comprehensive set of practice recommendations for effective genetic cancer risk assessment, counseling and testing for hereditary breast and ovarian cancer. The intended audience is genetic counselors and other health professionals who care for individuals with, or at increased risk of, hereditary breast and/or ovarian cancer.

Abstract CN03-01: Predictors of change in colorectal cancer screening decision stage among participants in a randomized, controlled trial of genetic and environmental risk assessment

Abstract Purpose. This report presents findings from a randomized, controlled trial of colorectal cancer (CRC) genetic and environmental risk assessment (GERA). Predictors of positive change in CRC screening decision stage (SDS) were identified among participants who completed a baseline and follow-up survey. Methods. A total of 493 primary care patients who were 50 to 79 years of age, were eligible for CRC screening were randomized to a GERA Group (n=328) or a usual care Control Group (n=165). GERA Group participants underwent decision counseling about GERA, had a blood draw to assess CRC risk, and received risk feedback (modestly-elevated or average risk) based on the combined presence of SNPs 677C&amp;gt;T and/or 1298A&amp;gt;C of the methylenetetrahydrofolate reductase (MTHFR) gene and serum folate level. Participants received a CRC screening kit and completed a follow-up telephone survey. Univariable analyses and multivariable regression were performed to determine if baseline screening sociodemographic and lifestyle factors, knowledge, psychosocial factors, stress about CRC, SDS, and risk status predicted self-reported change in SDS. Results. Participants were: female (56%), white (61%), 50 to 59 years of age (66%), &amp;gt; high school education (71%), and married (55%). Overall, SDS was as follows: decided against (1%), undecided (11%), and decided to do (87%) screening. 38% of participants exhibited a positive change in SDS to a higher decision stage, including actual screening. Positive SDS change by study group was: GERA Group (39%) and Control Group (34%). Multivariable analyses for all participants showed that knowledge was a positive predictor (p=0.006) of SDS change, as were lower CRC stress and lower SDS (p=0.023 and p&amp;lt;0.001, respectively). 12% of GERA Group participants had an elevated risk for CRC. Positive SDS change in the GERA Group by risk status was: elevated risk (36%) and average risk (42%). In the GERA Group, knowledge was a positive, nonsignificant predictor (p=0.107) of SDS change, while lower CRC stress and lower SDS were significant positive predictors (p=0.038 and p&amp;lt;0.001, respectively). Conclusion. Exposure to GERA and feedback indicating modestly-elevated risk influenced change in SDS among participants who had greater knowledge about CRC screening, reported lower CRC stress, or had decided against about or were uncertain about CRC screening. Citation Format: Ronald E. Myers, Sharon Manne, Karen Ruth, James Cocroft, Randa Sifri, Barry Ziring, David Weinberg. Predictors of change in colorectal cancer screening decision stage among participants in a randomized, controlled trial of genetic and environmental risk assessment. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr CN03-01.

Closing the loop: an interactive action-research conference format for delivering updated medical information while eliciting Latina patient/family experiences and psychosocial needs post-genetic cancer risk assessment.

A patient/family-centered conference was conducted at an underserved community hospital to address Latinas' post-genetic cancer risk assessment (GCRA) medical information and psychosocial support needs, and determine the utility of the action research format. Latinas seen for GCRA were recruited to a half-day conference conducted in Spanish. Content was partly determined from follow-up survey feedback. Written surveys, interactive discussions, and Audience Response System (ARS) queries facilitated the participant-healthcare professional action research process. Analyses included descriptive statistics and thematic analysis. The 71 attendees (41 patients and 27 relatives/friends) were primarily non-US born Spanish-speaking females, mean age 43years. Among patients, 73% had a breast cancer history; 85% had BRCA testing (49% BRCA+). Nearly all (96%) attendees completed the conference surveys and ARS queries; ≥48% participated in interactive discussions. Most (95%) agreed that the format met their personal interests and expectations and provided useful information and resources. Gaps/challenges identified in the GCRA process included pre-consult anxiety, uncertainty about reason for referral and expected outcomes, and psychosocial needs post-GCRA, such as absorbing and disseminating risk information to relatives and concurrently coping with a recent cancer diagnosis. The combined action research and educational conference format was innovative and effective for responding to continued patient information needs and addressing an important data gap about support needs of Latina patients and family members following genetic cancer risk assessment. Findings informed GCRA process improvements and provide a basis for theory-driven cancer control research.