Cancer Genetic Services Research Articles

Points to consider: is there evidence to support BRCA1/2 and other inherited breast cancer genetic testing for all breast cancer patients? A statement of the American College of Medical Genetics and Genomics (ACMG)

Points to consider: is there evidence to support BRCA1/2 and other inherited breast cancer genetic testing for all breast cancer patients? A statement of the American College of Medical Genetics and Genomics (ACMG)

Exploring the barriers preventing Indigenous Australians from accessing cancer genetic counseling.

In Australia, individuals of Aboriginal and Torres Strait Islander descent (Indigenous Australians) have poorer health outcomes than the general population, including higher incidence of cancer and reduced life expectancy up to 14years compared to non-Indigenous Australians. Although differences in engagement with healthcare and beliefs about disease/cancer exist between Indigenous communities, a number of common barriers have been identified hindering attendance at mainstream health services. To inform exploration of barriers that may impact access to a cancer genetic counseling service, consultations with Aboriginal stakeholders were undertaken. Ethical principles for studies that engage Indigenous communities were followed throughout the research endeavor. Using a stakeholder-endorsed focus group approach, the views of an Aboriginal Elders group (n=9) were sought with additional semi-structured interviews with social science and genetics researchers working with Indigenous communities in Australia (n=7). Thematic analysis of the results identified three themes: explanatory models of illness, barriers to keeping well and attending services, and recommendations for improvements to access/attendance. Barriers common to accessing both mainstream health services and clinical genetic services were identified, including attributions of illness and cancer. Specific genetic counseling barriers included the cultural inclusivity and accessibility of services, and a lack of awareness of genetic counseling both in the community and by clinicians unfamiliar with genetics. Recommendations included developing flexible service delivery models and culturally appropriate resources for Indigenous patients. These findings may inform future studies to improve Indigenous health outcomes and promote a more accessible, culturally appropriate approach to provision of cancer genetics services for Australia's First Peoples.

Abstract P6-08-15: Racial and ethnic variation in BRCA1 and BRCA2 genetic test results among individuals referred for genetic counseling at a large urban comprehensive cancer center

Abstract Background It is estimated that up to 10% of women diagnosed with breast cancer in the United States have a BRCA1 or BRCA2 inherited susceptibility, which accounts for approximately 125,000 women. There are racial and ethnic differences in the prevalence and types of pathogenic mutations and variants of uncertain significance (VUS) in BRCA1 and BRCA2. To better understand the prevalence of recurring pathogenic mutations and/or uncover novel mutations in specific racial and ethnic groups, we evaluated the mutational profile of individuals who had genetic counseling and testing at a large urban NCI designated Comprehensive Cancer Center. Methods Data was extracted from the Karmanos Cancer Institute (KCI) Cancer Genetic Counseling Service database over a 19 year period through 12/31/18. The cohort consisted of 5,929 individuals evaluated for high-risk of hereditary disease at 6 sites across Michigan including Detroit. We estimated the prevalence of BRCA1/2 pathogenic mutations and variants of uncertain significance (VUS) by race and ethnicity. Odds Ratios (OR) and 95% confidence intervals (CI) were calculated to compare the rate of pathogenic and VUS mutations in race and ethnic groups with non-Hispanic whites (NHW) indicated as the reference group. Results There were 3,114 (52.5%) unrelated individuals who underwent clinical BRCA1/2 testing. The racial/ethnic breakdown of the cohort included: 68.4% NHW, 21% African American (AA), 2.7% Ashkenazi Jewish (AJ), 2.2% Arab, 0.9% Hispanic (H), and 4.8% other. There were 290 individuals with pathogenic mutations (137 BRCA1 and 153 BRCA2) and 186 with VUS (61 BRCA1 and 125 BRCA2). For BRCA1, there were no differences by race and ethnicity in pathogenic mutations, however AA and Arab individuals were more likely to have VUS compared to NHW (OR & 95% CI, 2.63, 1.53-4.54 and 3.39, 1.01-11.41) respectively. For BRCA2, AJ individuals were more likely to have pathogenic mutations compared to NHW (OR & 95% CI, 2.51, 1.22-5.17) and both AA and AJ individuals were more likely to have VUS (OR & 95% CI, 1.55, 1.02-2.35 and 3.15, 95% CI 1.46-6.79) respectively. The table lists the most common pathogenic mutations seen in BRCA1 and BRCA2 by race and ethnicity. All mutations are unique and seen in more than one person unless indicated. Conclusions AA, Arab and AJ individuals were more likely to have VUS in BRCA1&BRCA2 than NHW suggesting the importance of variant reclassification in understanding cancer risk in racial and ethnic minority groups. Understanding the prevalence of BRCA1/2 mutations in specific racial and ethnic groups can potentially lead to customization of genetic testing and possible classification of new founder mutations. The most common pathogenic mutations by race and ethnicityRace/EthnicityBRCA1 (n)BRCA2 (n)% of Total MutationsNHWp.Glu1756Pro (14)p.Ile605Asn (7)p.Cys61Glu (5)p.Arg645Glu (2)p.Ser1253Arg (4)p.Ala938Pro (2)BRCA1: 28/102=27.5%p.Lys894Thr (3)p.Glu2198Asn (2)BRCA2: 17/103=16.5%p.Asp825Glu (2)2)p.Gln1886Ter (2)p.Asn312Ile (2)AA5296del4 (2)p.Gly1013Glu (2)IVS16+6T>C (2)p.Lys2496Ter (2)BRCA1: 6/23=26.1%p.Thr276Ala (2)p.Lys936Asn (2)BRCA2: 8/32=25%p.Lys1872Asn (2)AJp.Glu23Val (1)p.Ser1982Arg (5)BRCA1: 1/1=100%BRCA2: 5/9=55.6%Arabp.Gln12X(1)p.Ile1859Lys (2)BRCA1: 1/5=20%BRCA2: 2/3 = 66.7%Hispanicp.Arg71Gly (1)p.Glu1308Ter (1)BRCA1: 1/1=100%BRCA2: 1/1=100% Citation Format: Michael Steven Simon, Nadline Abdallah, Hadeel Assad, Rachel Reagle, Nancie Petrucelli, Kristen Purrington. Racial and ethnic variation in BRCA1 and BRCA2 genetic test results among individuals referred for genetic counseling at a large urban comprehensive cancer center [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-08-15.

Abstract P6-08-22: Racial and ethnic variation in multi-gene panel genetic test results among individuals referred for genetic counseling at a large urban comprehensive cancer center

Abstract Background There are racial and ethnic differences in the prevalence and types of pathogenic mutations and variants of uncertain significance (VUS) in BRCA1 and BRCA2. Since the landmark May 13, 2013 Supreme Court Ruling invalidating the patent for BRCA1 and BRCA2 genetic testing, numerous gene panels have been utilized to identify individuals at high risk for hereditary disease due to mutations in other cancer predisposing genes. To better understand the prevalence of recurring pathogenic mutations and/or uncover novel mutations in specific racial and ethnic groups, we evaluated the mutational profile of individuals who had genetic counseling and testing at a large urban NCI designated Comprehensive Cancer Center. Methods Data was extracted from the Karmanos Cancer Institute (KCI) Cancer Genetic Counseling Service data base from May 13, 2013 through December, 31, 2018. The cohort consisted of 3,544 unrelated individuals evaluated for high-risk of hereditary disease and 1,868 who had panel testing at 6 sites across Michigan including Detroit. We estimated the prevalence of pathogenic mutations and VUS from multigene panels by race and ethnicity. Odds Ratios (OR) and 95% confidence intervals (CI) were calculated to compare the rate of pathogenic mutations and VUS in race and ethnic groups with non-Hispanic whites (NHW) indicated as the reference group. Results There were 1,868 (52.7%) individuals who had panel testing which included 67.4% NHW, 24.1% African American (AA), 2.2% Arab, 1.9% Ashkenazi Jewish (AJ), 1.0% Hispanic (H), and 3.4% other. There were 174 individuals with pathogenic mutations and 312 with VUS. Compared to NHW, AA individuals were less likely to have pathogenic mutations on multi-panel testing (OR, 95% CI, 0.20, 0.10-0.37) and more likely to have VUS (OR, 95% CI, 1.41, 1.07-1.85). There were no differences in pathogenic mutations or VUS for other race or ethnic groups. Within a common 18 gene panel (excluding BRCA1 and BRCA2), the five most common genes with a pathogenic mutation were ATM (23), CHEK2 (21), PALB2 (13) and MSH6 (11). The three most common genes and number of pathogenic mutations identified by race and ethnicity were NHW (ATM -21, CHEK2-21&MSH6 -8), AA (MSH6-1, RAD51C-1&TP53-1), and Arab (PALB2-2, RAD50-1 and BARD1-1). For AJ individuals there were 2 pathogenic mutations identified in the MSH6 gene. There were no pathogenic mutations seen in Hispanics. Conclusions Understanding the prevalence of mutations in multi-gene panels in specific racial and ethnic groups can lead to better identification of individuals at risk for hereditary cancer who can benefit from enhanced surveillance and risk reducing management. Citation Format: Michael Steven Simon, Nadine Abdallah, Hadeel Assad, Malini Surapaneni, Rachel Reagle, Nancie Petrucelli, Kristen Purrington. Racial and ethnic variation in multi-gene panel genetic test results among individuals referred for genetic counseling at a large urban comprehensive cancer center [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-08-22.

Oncology Clinic-Based Hereditary Cancer Genetic Testing in a Population-Based Health Care System.

New streamlined models for genetic counseling and genetic testing have recently been developed in response to increasing demand for cancer genetic services. To improve access and decrease wait times, we implemented an oncology clinic-based genetic testing model for breast and ovarian cancer patients in a publicly funded population-based health care setting in British Columbia, Canada. This observational study evaluated the oncology clinic-based model as compared to a traditional one-on-one approach with a genetic counsellor using a multi-gene panel testing approach. The primary objectives were to evaluate wait times and patient reported outcome measures between the oncology clinic-based and traditional genetic counselling models. Secondary objectives were to describe oncologist and genetic counsellor acceptability and experience. Wait times from referral to return of genetic testing results were assessed for 400 patients with breast and/or ovarian cancer undergoing genetic testing for hereditary breast and ovarian cancer from June 2015 to August 2017. Patient wait times from referral to return of results were significantly shorter with the oncology clinic-based model as compared to the traditional model (403 vs. 191 days; p < 0.001). A subset of 148 patients (traditional n = 99; oncology clinic-based n = 49) completed study surveys to assess uncertainty, distress, and patient experience. Responses were similar between both models. Healthcare providers survey responses indicated they believed the oncology clinic-based model was acceptable and a positive experience. Oncology clinic-based genetic testing using a multi-gene panel approach and post-test counselling with a genetic counsellor significantly reduced wait times and is acceptable for patients and health care providers.

Organizational readiness to implement population-based screening and genetic service delivery for hereditary cancer prevention and control.

Despite clinical guidelines, programs conducting population-based screening and genetic service delivery for hereditary cancer prevention and control are rare in practice. We interviewed individuals (n=13) instrumental in implementing seven unique clinical programs conducting either universal tumor screening for Lynch Syndrome or routine family history screening and provision of genetic services for hereditary breast and ovarian cancer in the United States. To characterize determinants of readiness to implement population-based cancer genetic service delivery models, interviews and deductive codes drew on Weiner's theory of organizational readiness for change. Qualitative analysis identified themes across programs. The degree to which organizational stakeholders valued moving to a population-based genetic service delivery model depended on the existence of aligned clinical guidelines at the time of program implementation. However, judgments of implementation capacity within the organization, particularly with respect to task demands and resource concerns, were more often barriers to readiness. Program champions were essential to facilitating readiness, frequently taking on substantial uncompensated work. These data suggest that developing interventions targeting change efficacy and cultivating practice change champions may be two promising ways to increase uptake of population-based hereditary cancer screening and genetic service delivery in clinical practice.

Study on the differences of opinions and choices of high-risk breast cancer populations in China before and after genetic testing.

BackgroundIn recent years, genetic testing (GT) has developed rapidly in China. However, the cancer genetic service system is still immature in China. Little is known about the opinions around genetic counseling (GC) and GT in Chinese individuals at high risk of breast cancer. This work aims to understand the changes in awareness, attitudes, and willingness of high-risk populations before and after GT, as well as the possible barriers to GC/GT.MethodsSeveral questionnaires for the high-risk populations of breast cancer were completed. Then, some patients were selected for free single/multi-gene testing as well as further survey and statistical analysis.ResultsDespite low levels of awareness, Chinese high-risk breast cancer groups hold positive attitudes about GC/GT. There were differences in the willingness of different groups of high-risk people. After GT, different testing results led to different views and choices for the patients than before GT. Lack of genetic knowledge of breast cancer, misunderstanding, cost, fear of adverse effects, and policy market factors are obstacles to accepting GC/GT for the participants.ConclusionsChinese doctors need to communicate according to the specific situation of high-risk individuals in pre-test counseling and post-test counseling. The national policy and GT market also need to be improved to support the hereditary breast cancer families’ follow-up service system.

Knowledge and opinions regarding BRCA1 and BRCA2 genetic testing among primary care physicians

BRCA1 and BRCA2 (BRCA1/2) testing is standard for individuals with personal and/or family history suggestive of hereditary breast and ovarian cancer syndrome. The indications for testing have been expanding. To accommodate the need, incorporation of cancer genetic services into the practice of non-genetic healthcare providers should be considered. We carried out a survey to evaluate the knowledge and opinions regarding BRCA1/2 testing among primary care providers. The survey was sent to 245 Obstetrics/Gynecology and 97 Family Medicine physicians in the UPMC network. Eighty-six completed the survey between July 2015 and September 2015. The average correct responses to knowledge questions was 73%. A few respondents reported being completely confident, and ~50% reported being somewhat confident, in providing BRCA1/2-related information. Respondents selected genetic specialists and oncologists as the most qualified to provide cancer genetic services. Several perceived barriers and motivating factors to the implementation of BRCA1/2 testing in primary care were identified. The findings from this study suggested that primary care providers were not uniformly ready to provide BRCA1/2 genetic testing. Availability of professional society guidelines and evidence of testing's usefulness might motivate the incorporation of BRCA1/2 genetic testing into primary care practices. These findings would help guide future educational efforts to promote provision of cancer genetic services by non-genetic professionals.

Evaluating empowerment in genetic counseling using patient-reported outcomes.

Data about patient reported outcomes from cancer genetics services (CGS) are lacking but are essential to guide service evaluation and improvements. We measured improvement in empowerment, following genetic counseling in Singapore using a culturally-adapted version of the Genetic Counseling Outcome Scale (GCOS-24); and sought to identify factors associated with change in empowerment. The GCOS-24 was administered to 155 patients of the CGS, at pre- and post-counseling or testing timepoints. Of which, 110 patients underwent genetic testing. Individual pre- and post-counseling responses were subjected to Rasch analysis; the scale was subsequently split into cognitive control (CC) and emotional control (EC) domains. Associations of baseline characteristics with changes in pre- and post-CC and EC scores were assessed using multiple regression analysis. Both CC and EC scores showed significant improvement following genetic counseling and testing. While all items in the CC domain of being showed increases at follow-up, aspects of EC related to alleviating negative emotions (P = .88) and hopelessness (P = .2) did not show significant improvement. Our study revealed significant improvement in empowerment in patients who have received cancer genetic counseling, while revealing a need to cultivate hope and facilitate the alleviation of negative emotions in patients during genetic counseling.

STELO: a new tool for family physicians for the correct identification of inherited cancer syndromes.

The hereditary cancer syndromes represent overall <10% of all cancers. These syndromes are not irrelevant for public health because all the cancers typical of these syndromes affected young people and many members of the same family and the cancers are more aggressive than the sporadic ones and need specific surgery and medical therapy. We developed a new family assessment tool: STELO designed for family physicians to identify patients could benefit from Cancer Genetic Counselling. Test the sensitivity and specificity of a new assessment tool for the correct identification of inherited cancer syndromes. Retrospectively we tested the new tool on a subset of patients who had already undergone genetic counselling at the Cancer Genetic Counselling Service of ASST (Azienda Socio Sanitaria Territoriale) Settelaghi Varese, to investigate sensitivity, specificity and applicability of this new tool in routine genetic screening. STELO responses were matched against the opinion of two cancer geneticists (i.e. gold standard) who blinded each other decided if the history of these patients was properly suspected as a hereditary cancer syndrome. The Genetic Counselling Service followed 546 subjects from 2014 to 2015. STELO tool was tested retrospectively on these clinical records and resulted positive in 418 cases, out of 546 (76.5%). STELO reported, towards the gold standard, 88.5% and 52.3% of sensitivity and specificity, respectively. STELO has demonstrated to have a good sensitivity. The specificity was expectedly low given that STELO has been developed for general medicine, so it needs to be simple, practical, of rapid consultation and effectively used in clinical practice.

Multidisciplinary interventions in a specialist Drug Development Unit to improve family history documentation and onward referral of patients with advanced cancer to cancer genetics services

BackgroundMolecular aberrations in cancer may represent therapeutic targets, and, if arising from the germline, may impact further cancer risk management in patients and their blood relatives. Annually, 600–700 patients are referred for consideration of experimental drug trials in the Drug Development Unit (DDU) in our institution. A proportion of patients may merit germline genetic testing because of suspicious personal/family history or findings of tumour-based testing. We aimed to assess the impact of different multidisciplinary interventions on family history taking and referral rates from DDU to Cancer Genetics Unit (CGU). MethodsOver 42 months, three interventions were undertaken at different intervals: (1) embedding a genetics provider in the DDU review clinic, (2) ‘traffic light’ system flagging cancers with a heritable component and (3) virtual multidisciplinary meeting (MDM). Comparative analyses between intervals were undertaken, including referral rates to CGU, investigations and patient outcomes. Family history taking in a sample of 20 patients managed in each interval was assessed by a retrospective chart review. ResultsFrequency of family history taking and referral to CGU, increased with each intervention, particularly, the virtual MDM (40% vs 85%). Referral rates increased over the study period, from 0.1 referral/week (5/year, 0.36% total referrals) to 1.2/week (projected 63/year, 3.81%). Forty-four (52%) patients referred required germline testing; in three of whom, variants were identified. Non-attendance rates were low (6, 7%). ConclusionPatients in the DDU are unique, with long cancer histories and often short estimated life expectancy. Multidisciplinary working between CGU and DDU facilitates germline testing of those patients who may otherwise miss the opportunity.

Exploring Predictors of Genetic Counseling and Testing for Hereditary Breast and Ovarian Cancer: Findings from the 2015 U.S. National Health Interview Survey.

Despite efforts to increase the availability of clinical genetic testing and counseling for Hereditary Breast and Ovarian (HBOC)-related cancers, these services remain underutilized in clinical settings. There have been few efforts to understand the public’s use of cancer genetic services, particularly for HBOC-related cancers. This analysis is based on data from the 2015 National Health Interview Survey (NHIS), a U.S.-based nationwide probability sample, to better understand the public’s use of HBOC-related clinical cancer genetic services. Bivariate analyses were used to compute percentages and examine the associations of familial cancer risk for three genetic services outcomes (ever had genetic counseling for cancer risk, ever discussed genetic testing for cancer risk with a provider, and ever had genetic testing for cancer risk). Multivariable logistic regression models were used to estimate the association of familial cancer risk and other demographic and health variables with genetic services. Most women (87.67%) in this study were at low risk based on self-reported family history of breast and ovarian cancer, 10.65% were at medium risk, and 1.68% were at high risk. Overall, very small numbers of individuals had ever had genetic counseling (2.78%), discussed genetic testing with their physician (4.55%) or had genetic testing (1.64%). Across all genetic services outcomes, individuals who were at higher familial risk were more likely to have had genetic counseling than those at lower risk (high risk: aOR = 5.869, 95% CI = 2.911–11.835; medium risk: aOR = 4.121, 95% CI = 2.934–5.789), discussed genetic testing (high risk: aOR = 5.133, 95% CI = 2.699–9.764; medium risk: aOR = 3.649, 95% CI = 2.696–4.938), and completed genetic testing (high risk: aOR = 8.531, 95% CI = 3.666–19.851; medium risk aOR = 3.057, 95% CI = 1.835–5.094). Those who perceived themselves as being more likely to develop cancer than the average woman were more likely to engage in genetic counseling (aOR = 1.916, 95% CI = 1.334–2.752), discuss genetic testing (aOR = 3.314, 95% CI = 2.463–4.459) or have had genetic testing (aOR = 1.947, 95% CI = 1.13–3.54). Personal cancer history was also a significant predictor of likelihood to have engaged in genetic services. Our findings highlight: (1) potential under-utilization of cancer genetic services among high risk populations in the U.S. and (2) differences in genetic services use based on individual’s characteristics such as self-reported familial risk, personal history, and beliefs about risk of cancer. These results align with other studies which have noted that awareness and use of genetic services are low in the general population and likely not reaching individuals who could benefit most from screening for inherited cancers. Efforts to promote public awareness of familial cancer risk may lead to better uptake of cancer genetic services.

Improving access to cancer genetic services: perspectives of high-risk clients in a community-based setting.

Cancer genetic services are underutilized by high-risk clients in community-based health settings. To understand this disparity, 108 Planned Parenthood high-risk clients completed a utilization-focused survey. Clients expressed interest (78.8%) and intention (75.0%) in seeking genetic services. Personal/familial implications for cancer risk were the strongest motivators for seeking services (63.0-79.6%). Finances (39.6%) and worry (37.0%) were the biggest barriers. To reduce disparities in access to cancer genetics services, clinicians must understand clients' concerns and tailor their recommendations.

Adherence to guidelines for the referral of patients with colorectal cancer and abnormal tumour tissue testing for assessment of Lynch syndrome.

To determine the proportion of patients with colorectal cancer and abnormal immunohistochemistry testing of tumour tissue who were referred to a cancer genetic clinic for genetic counselling and possible germline testing of a blood sample for Lynch syndrome. This is a retrospective cohort study of patients with colorectal cancer and abnormal immunohistochemistry tumour tissue testing from St Vincent's Hospital (between November 2007 and December 2016). Patient list was compared against a state-wide database TrakGene to ascertain the overall referral rate for these patients. Of 216 patients, the total referral rate was 33.8% (n = 73), of which 27.8% (n = 60) were referred to St Vincent's Hospital's Cancer Genetics Service, 6% (n = 13) were referred externally and the remaining 66.2% (n = 143) were not referred. Binomial regression analysis performed displayed that age influenced likelihood of referral, where patients were 7.7% more likely to be referred for every decreasing year in age (P = 0.0004). Some clinicians were 4.3 times more likely to refer patients compared to others (P = 0.002). Suboptimal patient uptake for cancer genetics evaluation was found. Identifying barriers to patient referral should lead to changes that increase patient referrals. This will ensure that patients receive adequate education, counselling and management of Lynch syndrome. It would also allow for the identification of further at-risk relatives for whom preventative strategies can be employed. In addition, identification of relatives not at risk by genetic testing will liberate them from unnecessary colonoscopies. Discussion with the clinicians involved has since allowed for copies of the immunohistochemistry results to be forwarded by the Pathology Department to the Cancer Genetics Unit for checking and follow up with the clinician to ensure that their patients are aware of the result and have been offered referral for cancer genetic evaluation. This process is subject to ongoing audit.

Impact of Implementing B-RSTTM to Screen for Hereditary Breast and Ovarian Cancer on Risk Perception and Genetic Counseling Uptake Among Women in an Academic Safety Net Hospital

BackgroundLower socioeconomic status is strongly associated with decreased perception of cancer risk. Fewer low socioeconomic status women than expected currently access cancer genetic services from which they may benefit. Patients and MethodsWe screened women presenting for a screening mammogram at a safety net academic hospital using the Breast Cancer Genetics Referral Screening Tool Version 3.0 (B-RSTTM), an online tool designed to identify individuals potentially at risk for hereditary breast and ovarian cancer. Participants screening either positive (high risk) or negative (moderate risk) were offered genetic counseling appointments. We used a brief survey to evaluate change in risk perception before and after using B-RSTTM, and after a genetic counseling appointment, if applicable. Barriers to accepting appointments were assessed when participants declined. ResultsOf the 126 participants, 91 (72.2%) screened negative-average risk, 13 (10.3%) screened negative-moderate risk, and 22 (17.5%) screened positive. Of those who screened positive or negative-moderate, 24 (68.6%) expressed interested in a genetic counseling appointment, of which 19 (79.2%) scheduled. Four of the 19 scheduled (21.1%) completed the appointment. We found a significant difference in the number who rated their breast cancer risk correctly on the post-test between the groups who self-rated as low, moderate, or high risk. Those who perceived themselves as high risk were the most likely to rate their risk correctly on the post-test (P < .001). ConclusionWe showed that using B-RSTTM in a safety net academic hospital was effective at identifying women at increased risk for hereditary breast and ovarian cancer.

Genetic counseling processes and outcomes among prostate cancer patients (ProGen).

TPS343 Background: Prostate cancer (PC) is among the leading causes of cancer mortality in males. Recent studies found 8-12% of advanced PC cases may be hereditary. Germline mutations have been reported in BRCA1/2, other DNA repair genes including ATM, CHEK2, PALB2 and DNA mismatch repair genes. Genetic testing can inform treatment decisions including drug targeting, such as PARP inhibitors for men with BRCA mutations, and checkpoint inhibitors for those with pathogenic mutations in mismatch repair genes2. Discovering a pathogenic mutation associated with increased cancer risk also prompts dissemination of this information to family, where subsequent testing can lead to risk stratification and impactful opportunities for cancer screening and prevention. It is critical that men with high risk and potentially lethal prostate cancer routinely be offered genetic testing as a component of their cancer care. Genetic counseling services are limited, and more efficient services are needed. Methods: We are investigating video education prior to genetic testing compared with in-person pretest counseling with a licensed genetic counselor (GC). ProGen is an ongoing randomized trial evaluating two distinct models of cancer genetics service delivery in 450 PC cases over a two-year period. The study is conducted in collaboration with Ambry Genetics utilizing a 67-gene cancer panel. The primary aim is analysis of the proportion and type of germline mutations identified. Secondary aims include testing uptake by arm, evaluation of distress, knowledge, satisfaction with testing services, family communication, and impact on cancer care. Results are communicated by telephone with a GC. Inclusion criteria are: potentially lethal PC (metastatic, localized with Gleason score ≥8, rising/persistent PSA after local therapy), early diagnosis (≤ 55 years), prior malignancy, and/or family history potentially indicating a hereditary cancer risk. Enrollment is 74% completed at a single institution. (NCT03328091). 1 Pritchard CC, et al. Inherited DNA‐repair gene mutations in men with metastatic prostate cancer. NEJM. 2016;375:443 2 Mateo J, et al. DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer. NEJM . 2015;373(18):1697-1708 Clinical trial information: NCT03328091.

DNA diagnosis and the emergence of cancer genetic services in European health care.

DNA diagnosis and the emergence of cancer genetic services in European health care.

Abstract PD6-12: Evaluating racial disparities in breast cancer referrals for hereditary risk assessment

Abstract Background: There is a pronounced onco-racial disparity in Washington, D.C., which had the highest national incidence of breast cancer in African Americans (AA) patients in between 2010-2015 and the worst outcomes (American Cancer Society). Recent data indicates a higher incidence of deleterious BRCA1 [and BRCA2] mutations and variants of uncertain significance (VUS) in AA patients compared to Caucasian (C) patients when controlled for patients of Ashkenazi Jewish (AJ) populations (Hall 2009). Despite this, AA women meeting National Comprehensive Cancer Network (NCCN) criteria for genetic testing are less likely to complete such testing compared to C women nationally. Studies have investigated psycho-social drivers of minority patient aversion to genetic testing. We hypothesize that lack of physician referral for cancer genetic counseling and testing for AA women contributes to this disparity. Methods: The George Washington Cancer Center (GWCC) Registry was used to identify non-Hispanic African Americans (BNH) and non-Hispanic whites (WNH) treated for breast cancer between 2014-2018. Of those individuals selected for inclusion were those who met select NCCN criteria for referral for genetic evaluation including breast cancer diagnosis under age 50, triple negative breast cancer (TNBC) under age 60, and two primary breast cancers. Only BNH and WNH individuals were included. Excluded patients were those who were not BNH or WNH or who did not meet the NCCN criteria listed above. Patients were then stratified by race according to who underwent genetic evaluation, whether at our Ruth Paul Cancer Genetics and Prevention Service (RPCGPS) or elsewhere, by reviewing GWCC, RPCGPS, and patient clinic records for genetic testing results from outside institutions. Patient charts were used to identify individuals who received a physician referral over the course of their cancer care. Results: 1180 patients were treated at the GWCC for breast cancer (both in situ and invasive carcinoma) between 2014–2018. Of those, BNH n=502; WNH n=435. Twenty-seven percent of BNH and WNH patients met the study criteria for referral for genetic evaluation (n=252; BNH n=115, WNH n=137), including breast cancer diagnosis under age 50 (BNH n=76; WNH n=108), TNBC under age 60 (BNH n=14; WNH n=5), and two primary breast cancers (BNH n=18, WNH n=16). Several patients identified met two or more criteria for referral (BNH n=7, WNH n=8). Physician referral rates differed significantly by race (BNH 76%, n=87 and WNH 91%; n=125; χ2=11.4, p-value&amp;lt;0.001). Of referred patients, there was no significant difference in those who followed-up at RPCGPS by race (BNH 93%, n=81; WNH= 93%, n=116, χ2 =0.0072, p-value=0.93). Conclusions: Low genetic testing rates for AA breast cancer patients are an impediment to resolving the prominent onco-racial breast cancer disparities. This study identified physician referral as a potential contributor to racial disparity in the utilization of cancer genetics services. Potential reasons for the discrepancy in referral may include lag in physician education on the topic of hereditary risk and barriers in physician-patient communication. These findings need to be confirmed and explored at other sites to help improve the identification of at-risk women in the AA community. Citation Format: Pepin A, Peterson J, Thomas R, Johnson K, Stark E, Biagi T, Kaltman R. Evaluating racial disparities in breast cancer referrals for hereditary risk assessment [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD6-12.

A patient-centered mobile health application to motivate use of genetic counseling among women with ovarian cancer: A pilot randomized controlled trial

ObjectiveDespite current guidelines recommending women with ovarian cancer receive genetic risk evaluation by a genetic counselor, utilization has historically been low. We sought to assess the feasibility and effectiveness of a week-long mobile Application for Genetic Information on Cancer (mAGIC) intervention aimed to persuade women with ovarian cancer to pursue genetic counseling. MethodsThe mobile application intervention was based on the Fogg Behavior Model, and consisted of three parts: (1) identifying barriers, (2) developing motivators, and (3) providing triggers to action. The Health Belief Model was used to guide content development. We conducted a prospective, randomized, controlled pilot trial among 104 untested women with a history of epithelial ovarian, primary peritoneal or fallopian tube cancer with the primary objective of increasing uptake of cancer genetic counseling services. ResultsUtilization of cancer genetic counseling services improved in both study arms over historical controls, however there was no statistically significant difference between them (intervention: 54.5% versus control: 38.6%; p = 0.14). However, compared to controls, women randomized to the mAGIC intervention demonstrated greater knowledge of hereditary cancer (0–10 scale; 9.4 ± 1.0 vs. 7.1 ± 1.5; p < 0.0001), which persisted for at least three months. Additionally, 96% of women in the intervention group reported they had talked with their family about genetic counseling compared to 77% in the control group (p = 0.01). ConclusionsThe mAGIC intervention did not result in increased uptake of genetic counseling, however it provided significant secondary benefits, including increased participants' knowledge about hereditary ovarian cancer, self-efficacy, and their reported communication with family members.ClinicalTrials.gov Identifier: NCT02877862

Global Disparities in Breast Cancer Genetics Testing, Counselling and Management.

Hereditary breast cancers, mainly due to BRCA1 and BRCA2 mutations, account for only 5-10% of this disease. The threshold for genetic testing is a 10% likelihood of detecting a mutation, as determined by validated models such as BOADICEA and Manchester Scoring System. A 90-95% reduction in breast cancer risk can be achieved with bilateral risk-reducing mastectomy in unaffected BRCA mutation carriers. In patients with BRCA-associated breast cancer, there is a 40% risk of contralateral breast cancer and hence risk-reducing contralateral mastectomy is recommended, which can be performed simultaneously with surgery for unilateral breast cancer. Other options for risk management include surveillance by mammogram and breast magnetic resonance imaging, and chemoprevention with hormonal agents. With the advent of next-generation sequencing and development of multigene panel testing, the cost and time taken for genetic testing have reduced, making it possible for treatment-focused genetic testing. There are also drugs such as the PARP inhibitors that specifically target the BRCA mutation. Risk management multidisciplinary clinics are designed to quantify risk, and offer advice on preventative strategies. However, such services are only possible in high-income settings. In low-resource settings, the prohibitive cost of testing and the lack of genetic counsellors are major barriers to setting up a breast cancer genetics service. Family history is often not well documented because of the stigma associated with cancer. Breast cancer genetics services remain an unmet need in low- and middle-income countries, where the priority is to optimise access to quality treatment.