Genetic Testing For Hereditary Breast And Ovarian Cancer Research Articles

Abstract A067: Perceptions and experiences of Black women on hereditary breast and ovarian cancer genetic testing

Abstract Black women experience significant disparities in morbidity and mortality related to hereditary breast and ovarian cancer (HBOC). Early identification of women with HBOC is essential for proactive screening and timely diagnosis but evidence suggests that Black women receive genetic testing for HBOC at lower rates than their White counterparts. To understand Black women’s perspectives on HBOC genetic testing and potential factors influencing this decision, we conducted in-depth qualitative interviews with 107 Black women with a personal or family history of breast or ovarian cancer. Participants were recruited via the networks of patient support organizations and sororities as well as at a family medicine safety net clinic in Jacksonville, FL. Participants frequently expressed a lack of awareness about their family cancer history; many cancer patients stated that they only became aware of extensive family history upon their own diagnosis. Lack of family history sharing was attributed to a culture of silence around medical issues and a desire to protect family members from difficult information. However, most participants indicated a strong desire to understand their own risk of HBOC and were interested in genetic testing. Participants with a personal diagnosis were motivated to undergo HBOC genetic testing to reduce the risk for future generations. Clinical experiences with the offer of HBOC genetic testing were variable, with a few expressing that they had to make repeated inquiries from a provider to understand the relevance of the test to their own health. These findings suggest that investigation into alternative clinical modalities to collect family health history may be beneficial to identify Black women who meet NCCN Guidelines for HBOC testing. In contrast to the literature suggesting hesitancy for HBOC genetic testing, many participants perceived genetic results as having a positive impact for their medical decision-making and family's health. The development of patient materials and provider education on cultural and social factors that influence the uptake of HBOC genetic testing is also needed. Citation Format: Kirsten A. Riggan, Michele Halyard, Sarah E. James, Marion Kelly, Daphne Phillips, Megan A. Allyse. Perceptions and experiences of Black women on hereditary breast and ovarian cancer genetic testing [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A067.

Management of ovarian and breast cancer risk in non-BRCA HBOC pathogenic variant carriers in a large California health care system

PurposeTo describe breast and ovarian cancer risk reduction strategies in the clinical management of women who test positive for non-BRCA hereditary breast and ovarian cancer (HBOC) pathogenic variants compared to those who test positive for pathogenic BRCA variants or have negative germline panel testing. MethodsExamination of imaging and preventive surgeries in women undergoing HBOC genetic testing from 1/1/2015 to 12/31/2018, with follow up to 03/31/2020 in Kaiser Permanente Northern California. ResultsA total of 13,271 tests which included HBOC genes were identified. Rate of bilateral salpingo-oophorectomy after genetic testing were similar for BRCA and the non-BRCA moderate risk ovarian pathogenic variants (PVs) (47.4% vs 54%, p = 0.25). Rates were lower for low risk or unknownrisk non-BRCA PVs (12.8%, p < 0.001, 5.3% (p < 0.001). Rates of surveillance for ovarian cancer with ultrasound and CA 125 in the first year was 63.3% and 64.7% for BRCA PV, 37.5% and 27.1%, for non-BRCA moderate risk PVs and 13.7% and 4.6%, for low-risk PVs. Bilateral mastectomy rates were 19.7% for BRCA PV, 10.1% (p = 0.028) for non-BRCA breast high risk PVs, for moderate risk PVs 7.7% (p < 0.001) and for unknown risk 0.4% (p < 0.001). MRI surveillance rates in the first year similarly were 47.4% for non-BRCA BRCA PV, 43% for breast high risk PV, 39.4% for moderate risk and 4.9% for unknown risk PV. ConclusionSurgical and surveillance strategies are underutilized for HBOC PV, however there is concordance of uptake of preventive strategies with specific risk associated with non-BRCA PVs.

Mother and Daughter Perspectives on Genetic Counseling and Testing of Adolescents for Hereditary Breast Cancer Risk

To evaluate the risks, benefits, and utility of testing for adult-onset hereditary breast and ovarian cancer (HBOC) in adolescents and young adults. We evaluated interest in genetic testing of adolescents for adult-onset HBOC genes through semistructured interviews with mothers and adolescents who had previously participated in breast cancer research or had pursued (mothers) clinical testing for HBOC. The majority of mothers (73%) and daughters (75%) were interested in the daughter having genetic testing and were motivated by the future medical utility and current social utility of relieving anxiety and allowing them to prepare. Mothers and daughters both reported that approximately 3years in the future was the best time to test the daughter regardless of the current age of the daughter. Overall, both mothers and daughters expressed the importance of the involvement of the mother to provide educational and emotional support but ultimately it was the daughter's decision to test. Balancing the independence and maturity of the daughter while reinforcing communication and support within the dyad was a prominent theme throughout the interviews. There is interest among some high-risk adolescents and young adults to engage in genetic counseling and undergo testing. Providing pretest and posttest genetic counseling, assessing preferences for parent involvement, and offering psychosocial support may be important if genetic testing for HBOC is offered to adolescents and young adults before age 25years.

Hereditary cancer screening at an urban safety net hospital.

10604 Background: Individuals with hereditary cancer syndromes (HCS) have a high lifetime risk of developing cancer. However, the rate at which at-risk individuals undergo genetic evaluation is low, particularly for individuals that belong to populations that are historically underserved. We sought to characterize the demographic factors that may be associated with receipt of recommended HCS evaluation and follow-up. Methods: All patients with pathologically confirmed breast, ovarian, or fallopian tube cancers and qualifying for hereditary breast and ovarian cancer (HBOC) testing based on NCCN guidelines from 2016 to 2021 at an urban safety-net hospital were included in this analysis. Institutional review board approval was obtained. Demographic and oncologic data, as well as HBOC genetic testing outcomes were collected through retrospective chart review using a standardized data collection tool. Univariate logistic regression models were constructed to test the association of variables with receiving hereditary cancer genetic testing. Results: A total of 312 patients were included in the analysis, 90% of which had breast cancer. Forty percent were non-English speaking, 31% were non-White, and 25% were uninsured. Overall, 70% of patients were referred for genetic counseling and 65% underwent testing. Our analysis showed higher association of genetic testing uptake with Spanish language [odds ratio (95% confidence interval)] [1.74 (1.04, 2.93)], stage II disease [2.15 (1.11, 4.16)], and having a referral to genetic counseling [9.21 (5.32, 15.96)]. A lower rate of genetic testing was associated with patients identifying as Black [0.36 (1.87, 0.70)], having Medicare insurance [0.29 (0.14, 0.61)], a higher Charlson Comorbidity Index [0.31 (0.13, 0.73)], and older age [0.94 (0.92, 0.96)]. Uninsured patients had a similar association with genetic testing uptake as patients with Medicaid. Variables seeming to have no association with genetic testing uptake include family history of cancer, type of cancer, performance status, substance use, and Latinx ethnicity. A pathologic variant was found in 13% of our population. A variant of unknown significance (VUS) was found in 33% of Hispanic or Latinx patients and in 46% of non-Hispanic or Latinx patients who received testing, for a combined VUS prevalence of 39%. Conclusions: Our analysis shows that genetic testing rates for patients meeting HBOC syndrome criteria at an urban, safety-net institution were higher than expected, particularly for Spanish speaking patients and those with Medicaid or no insurance. We hypothesize this may be due to the emphasis our institution places on the care of uninsured patients through programs to make services accessible, as well as strong engagement with the Spanish speaking community. These results can help guide future interventions to target patient groups with lower rates of genetic testing, as well as maintain the successes seen among our diverse population.

OP012: Perceptions of breast and ovarian cancer risk and genetic testing among Non-Hispanic Black women

Non-Hispanic Black (NHB) women experience health disparities from familial and hereditary breast and ovarian cancer (HBOC) compared to other racial and ethnic groups, including 40% higher mortality from breast cancer compared to non-Hispanic White women. One potential factor in these disparities includes lower uptake of HBOC genetic testing. This study explores potential factors for the lower use of HBOC genetic testing in NHB women and their families. Understanding these factors is critical to improving uptake of HBOC testing in the NHB community and improving HBOC racial and ethnic health disparities. A national sample of NHB women with personal or family history of HBOC were recruited through patient support organizations, historically Black colleges and university sororities, professional organizations for women of African descent, and snowball sampling. Participants were interviewed using an interview guide developed by content experts and a community advisory board. Interviews were audio recorded and transcribed verbatim. Interview transcripts were qualitatively analyzed using NVivo12 according to the principles of grounded theory. Sixty-one NHB women with personal (n=37, breast; n=6, ovarian) or family history (n=14, breast; n=2, ovarian; n=2 breast/ovarian) of HBOC participated in a qualitative interview. Participants reported on their own awareness of their family history of HBOC prior to their own diagnosis and how this informed their assessment of their pre-diagnostic risk of HBOC. The impact of family culture and cohesion, including perceptions of a familial ‘culture of silence’ around the sharing of personal or family medical history were also identified as potential barriers to awareness of HBOC risk. Thirty participants with a personal history and seven participants with family history received HBOC genetic testing upon recommendation of their provider or following their own request. Those that declined HBOC genetic testing described misperceptions of HBOC inheritance or expressed a belief that such testing would not be personally beneficial. Participants were also asked to describe family members’ interest in cascade testing and their reasons for accepting or declining HBOC genetic testing. Many participants felt that their daughters would be interested in HBOC genetic testing, but that siblings and other extended family members would decline out of belief that the results would have limited personal utility to themselves and/or their offspring or that a potential positive result would result in distress and life-long worry. Family members’ education status and views on healthcare were also thought to be important factors in their decision. This study is the largest qualitative study of its kind in NHB women with a personal or family history of breast and/or ovarian cancer. These findings suggests that there are significant barriers to HBOC genetic testing in the NHB community, including cultural factors influencing risk perception and the uptake of cascade testing. Culturally sensitive community outreach on the disparate impact of breast and ovarian cancer and how genetic testing may improve NHB cancer outcomes may improve uptake of HBOC genetic testing among at-risk NHB families.

Overview of hereditary breast and ovarian cancer (HBOC) guidelines across Europe

Hereditary breast and ovarian cancer (HBOC) is a syndrome defined by an increased risk of developing breast and/or ovarian cancer most commonly due to germline disease-causing variants in the BRCA1 and BRCA2 genes, but also other causative genes such as PALB2, ATM and CHEK2. As genetic testing becomes more prevalent and new clinical data emerge, updates of national guidelines are required to incorporate these advances in our knowledge. The aim of this work is to review the guidelines for HBOC genetic testing and clinical surveillance across European countries, mostly affiliated to the European Reference Network (ERN) for Genetic Tumor Risk Syndroms (GENTURIS). Young onset breast cancer (BC), triple negative phenotype, or bilateral BC are considered as criteria for genetic testing in all, with differences in age limits. Testing of invasive epithelial non-mucinous ovarian cancer is also universally accepted. While breast magnetic resonance imaging (MRI) is consistently recommended in high-risk individuals, age of onset for mammograms differ between 30 and 40 years. Risk-reducing mastectomy is commonly offered as an option, while risk-reducing salpingo-oophorectomy is universally recommended. The largest differences are observed with respect to ovarian surveillance prior to risk-reducing salpingo-oophorectomy and in breast surveillance for carriers of non-BRCA1/2 genes. These differences in national guidelines reflect the variations in clinical consensus that may be reached in the absence of consistent evidence for some recommendations.

"It wasn't just for me": Motivations and implications of genetic testing for women at a low risk of hereditary breast and ovarian cancer syndrome.

Genetic testing for hereditary breast and ovarian cancer (HBOC) due to pathogenic variants in BRCA1 or BRCA2 is why most women present to familial cancer centers. Despite being assessed as low risk for HBOC, many women proceed with genetic testing. This study explored the genetic testing experiences of unaffected women at low risk of HBOC to clarify what motivates these women to have testing, and what are the implications of the results. A qualitative approach was taken. Participants included women who had genetic testing for HBOC from 2016-2018 at the Parkville Familial Cancer Centre in Melbourne, Australia. In-depth, semi-structured interviews were conducted, and thematic analysis was undertaken on transcripts; transcripts were coded, codes were organized into a hierarchical system of categories/subcategories, and key themes were identified. Analysis of 19 transcripts identified five themes: family underpinned all motivators for HBOC genetic testing; health professionals were influential throughout the process; participants were planning for a positive result; results influenced screening-anxiety and frequency; and negative results gave participants relief in many different ways. The three participants with positive results reported feeling shocked at the results and empowered giving this information to family members. Women at low HBOC risk may be motivated to seek genetic testing, and access to this is increasingly offered through non-genetic health professionals. Professionals can support clients through genetic testing by recognizing familial experiences, providing accurate information, addressing risk perceptions, and understanding cancer anxiety felt by many women.

Abstract P6-08-16: Evaluation of a decision aid on BRCA1/2 genetic testing in Orthodox Jewish women

Abstract Background: Ashkenazi Jews have a 1 in 40 chance of carrying a BRCA1 or BRCA2 (BRCA1/2) pathogenic variant. Our prior research has shown that Orthodox Jewish women face unique social, cultural, and religious factors that may influence uptake of BRCA1/2 genetic testing. The aim of our study was to examine the impact of a web-based decision aid (DA) on BRCA1/2 genetic testing intention/uptake in Orthodox Jewish women. Methods: We conducted a pilot study among 50 Orthodox Jewish women in the New York/New Jersey area who were given access to the RealRisks DA and completed surveys at baseline prior to exposure to RealRisks and at 1 and 6 months after exposure to RealRisks. RealRisks is a patient-centered DA that includes family history intake, calculation of personalized breast cancer risk according to the BRCAPRO model, education about the pros and cons of genetic testing, and preference elicitation. The surveys collected information on participant demographics, health literacy, subjective numeracy, perceived breast cancer risk and BRCA1/2 mutation risk, breast cancer worry, stigma, hereditary breast and ovarian cancer (HBOC) genetic testing knowledge, autonomy, decision self-efficacy, decisional conflict, decision regret, and genetic testing intention/uptake. Descriptive statistics and paired t-tests and Chi-squared tests were conducted to assess changes in the study measures from baseline to follow-up. Results: Fifty women completed the baseline survey, 43 (86%) the 1-month survey, and 38 (74%) the 6-month survey. Mean age was 43.9 years (standard deviation [SD] 14.6); 94% had adequate health literacy and mean numeracy score was 4.25 (SD 0.83; range, 1-6). At baseline, 74% of women had adequate HBOC genetic testing knowledge and 52% thought it was likely that they carried an altered BRCA1/2 gene. Compared to baseline, there was a significant increase in HBOC genetic testing knowledge and decrease in decisional conflict at 1 month and 6 months. There was no significant change in decision self-efficacy, autonomy, stigma, or breast cancer worry after exposure to RealRisks at 1-month or 6-month follow-up. The percentage of women who intended to complete or already completed BRCA1/2 genetic testing decreased from 54% at baseline to 30% at 1 month. At 6 months, 21% reported they had completed or intended to complete BRCA1/2 genetic testing at that time. Conclusions: The RealRisks DA was effective at improving HBOC genetic testing knowledge and reducing decisional conflict about HBOC genetic testing; however, genetic testing intention decreased after exposure to the DA. An intervention that directly addresses the religious and cultural issues regarding genetic testing in the Orthodox Jewish community may improve BRCA1/2 genetic testing uptake and adoption of cancer prevention strategies in this population. Such an intervention will likely have to include religious, community, and medical leaders within the Orthodox Jewish community. Changes in study measures over 3 time pointsOutcome MeasuresBaseline Mean (SD)1 month Mean (SD)p-value compared to baseline6 months Mean (SD)p-value compared to baselineHBOC geneting testing knowledge [range, 0-11]6.60 (2.18)7.74 (1.94)&amp;lt;0.0017.24 (2.07)0.050Decision self-efficacy [range, 0-100]56.26 (15.63)55.39 (16.91)0.869Not Assessed (NA)Decisional conflict [range, 0-100]52.45 (28.43)33.93 (28.74)&amp;lt;0.00128.29 (27.64)&amp;lt;0.001Autonomy [range, 0-7]4.21 (1.43)4.36 (1.38)0.680NAStigma [range, 1-7]3.51 (1.15)3.25 (0.98)0.477NABreast cancer worry [range, 1-7]2.23 (1.03)2.27 (0.98)0.7672.26 (1.00)0.889HBOC genetic testing completion or intention to complete (%)54%30%0.02021%0.002 Citation Format: Meghna S Trivedi, Haley Manley, Haeseung Yi, Thomas Silverman, Wendy K Chung, Paul S Appelbaum, Rebecca Starck, Isaac Schechter, Rita Kukafka, Katherine D Crew. Evaluation of a decision aid on BRCA1/2 genetic testing in Orthodox Jewish women [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 P6-08-16.

Racial and Ethnic Differences in BRCA1/2 and Multigene Panel Testing Among Young Breast Cancer Patients

Genetic testing for hereditary breast and ovarian cancer (HBOC) is recommended for breast cancer patients diagnosed at age ≤ 50 years. Our objective was to examine racial/ethnic differences in genetic testing frequency and results among diverse breast cancer patients. A retrospective cohort study among women diagnosed with breast cancer at age ≤ 50 years from January 2007 to December 2017 at Columbia University in New York, NY. Among 1503 diverse young breast cancer patients, nearly half (46.2%) completed HBOC genetic testing. Genetic testing completion was associated with younger age, family history of breast cancer, and earlier stage, but not race/ethnicity or health insurance status. Blacks had the highest frequency of pathogenic/likely pathogenic (P/LP) variants (18.6%), and Hispanics and Asians had the most variants of uncertain significance (VUS), 19.0% and 21.9%, respectively. The percentage of women undergoing genetic testing increased over time from 15.3% in 2007 to a peak of 72.8% in 2015. Over the same time period, there was a significant increase in P/LP and VUS results. Due to uncertainty about the clinical implications of P/LP variants in moderate penetrance genes and VUSs, our findings underscore the need for targeted genetic counseling education, particularly among young minority breast cancer patients.

Population-based genetic testing of asymptomatic women for breast and ovarian cancer susceptibility

The identification of carriers of hereditary breast and ovarian cancer (HBOC) gene variants through family cancer history alone is suboptimal, and most population-based genetic testing studies have been limited to founder mutations in high-risk populations. Here, we determine the clinical utility of identifying actionable variants in a healthy cohort of women. Germline DNA from a subset of healthy Australian women participating in the lifepool project was screened using an 11-gene custom sequencing panel. Women with clinically actionable results were invited to attend a familial cancer clinic (FCC) for post-test genetic counseling and confirmatory testing. Outcomes measured included the prevalence of pathogenic variants, and the uptake rate of genetic counseling, risk reduction surgery, and cascade testing. Thirty-eight of 5908 women (0.64%) carried a clinically actionable pathogenic variant. Forty-two percent of pathogenic variant carriers did not have a first-degree relative with breast or ovarian cancer and 89% pursued referral to an FCC. Forty-six percent (6/13) of eligible women pursued risk reduction surgery, and the uptake rate of cascade testing averaged 3.3 family members per index case. Within our cohort, HBOC genetic testing was well accepted, and the majority of high-risk gene carriers identified would not meet eligibility criteria for genetic testing based on their existing family history.

Assessment of High Risk of Hereditary Breast and Ovarian Cancer (HBOC) and Acceptance for Genetic Testing Among Cases of Ovarian and Breast Cancer in Indian Set-up

To identify cases needing genetic testing for hereditary breast and ovarian cancer (HBOC) syndrome among cases of breast and ovarian cancer and assess their acceptability for genetic testing. One hundred patients of breast and/or ovarian cancer were recruited. A series of family meetings were done with patient and close family members. The first meeting was for pedigree chart preparation and identification of cases for genetic testing (HBOC) as per NCCN 2013 criteria. Second family meeting was held for counselling about genetic testing. Third meeting was held for recording acceptance or refusal for genetic testing. For those refusing the test, reasons for refusal were recorded. Outcome measures including prevalence of high-risk cases, acceptance rate for genetic testing and factors affecting the above acceptance rates among high-risk women were statistically analysed. Out of 100 patients of breast and ovarian cancer recruited in the study, 88 were found to be at high risk of HBOC. The most common criterion for high risk among breast cancer cases was age below 45 years. Family history of breast or ovarian cancer was present in 3.03% cases of ovarian cancer and 11.76 cases of breast cancer. Eleven (16.66%) cases of epithelial ovarian carcinoma and six (27.27%) cases of breast carcinoma accepted genetic testing. Socioeconomic status was found to have statistically significant correlation (p < 0.001 and p = 0.030) with acceptance for genetic testing. Though it is a small sample study, there is huge burden of women needing genetic testing for HBOC. There is lack of awareness about familial nature of disease and low acceptance for genetic testing in our population. There is a significant effect of socioeconomic status on acceptance for genetic testing.

Abstract P4-03-06: Limitations of direct-to-consumer genetic screening for HBOC: False negatives, false positives and everything in between

Abstract Background Genetic screening of unaffected individuals for hereditary breast and ovarian cancer (HBOC) risk is a growing opportunity for personalized preventive medicine. The FDA recently authorized a direct-to-consumer (DTC) test to report on 3 BRCA1/2 variants, commonly found in individuals of Ashkenazi Jewish (AJ) heritage, out of more than 1000 known. Here we define the probability that DTC genetic screening for the 3 BRCA1/2 AJ founder variants would falsely reassure individuals of AJ and non-AJ ancestry of low risk for hereditary cancer syndromes (HCS). We also assess the frequency of false positive results reported by third parties from raw genotypes, which are routinely provided to clients who submit them for cancer risk analysis. Methods We analyzed de-identified data on three cohorts: 1) An indication-based cohort of 119,328 patients referred by healthcare providers for HBOC genetic testing due to personal or family history, 2) a screening cohort of 5,170 patients without personal or family history who had BRCA1/2 testing as a health screen, and 3) a confirmation cohort of 102 patients referred for clinical confirmatory testing instigated by positive DTC results from third party analysis of raw data. Results In the indication-based cohort 12,846 patients had a mutation in any HCS-associated gene: 4,733 (37%) were in BRCA1/2, of which 12% were one of the 3 AJ founder mutations. Ethnicity impacted AJ founder mutation frequency: 81% of AJ patients with any BRCA1/2 mutation had one of the 3 founder mutations, but only 6% of non-AJ patients. Overall clinical false-negative rate for the 3 AJ founder mutations in BRCA1/2 carriers was 88%; rates were 19% and 94% among AJ and non-AJ individuals, respectively. In the screening cohort, where 2.6% were AJ, 40 patients had a P/LP mutation in BRCA1/2; 12.5% were an AJ founder mutation. The clinical false-negative rate of 88.5% for any BRCA1/2 mutations in the screening cohort is similar to the indication-based cohort. Finally, in the confirmation cohort, among patients told of a positive DTC screening result, our analyses indicated 50% (52/102) were analytic false positives. Conclusions This study highlights the limitations of screening restricted to a few of the many genetic variants associated with HBOC risk. We found a greater rate of non-founder BRCA1/2 mutations in AJ patients than previously reported, and found a concerning rate of clinical false negatives with screening limited to the AJ founder variants. Although increasing access to genetic information is vital, the limitations of current DTC genetic screening, despite warnings from the FDA, may not be well understood by consumers and should be used with caution. Patients screened for HBOC on a platform limited to the AJ founder variants and supplemented by analysis of raw genotyping data, should receive confirmatory testing, regardless of having either a positive or negative result, a recommendation which the DTC companies and third party analysts of raw data ostensibly support. These results suggest that all HCS screening should include the support of a qualified clinician to assess the potential limitations and implement appropriate clinical management recommendations for patients and their family members. Citation Format: Esplin ED, Haverfield E, Yang S, Herrera B, Anderson M, Nussbaum RL. Limitations of direct-to-consumer genetic screening for HBOC: False negatives, false positives and everything in between [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 P4-03-06.

The impact of the medicare benefits schedule on genetic testing in hereditary breast and ovarian cancer: An audit of test request practices in Western Australia

After the ‘Angelina Jolie effect’, a new paradigm in Australian genetic testing practices related to hereditary breast and ovarian cancer (HBOC) has emerged: on 1 November 2017 the Medicare Benefits Schedule (MBS) enabled specialists to request genetic testing of the BRCA1 and BRCA2 genes and one or more of the genes STK11, PTEN, CDH1, PALB2, or TP53 in patients with breast or ovarian cancer who are at greater than 10% risk of having a pathogenic variant in the interrogated genes.1 While the celebrity health disclosure increased awareness of the utility of HBOC genetic testing, and also of its potential overuse,2 the MBS introduction is likely to further increase awareness amongst specialists and to open earlier access to testing for a significant proportion of high-risk patients. We present the outcomes of an audit of requests for HBOC genetic testing at the Western Australian public pathology service, PathWest, for the period January 2016 – January 2018, with particular focus on changes in request practices following the MBS update.

Decision support for family history intake to determine eligibility for BRCA testing among multiethnic women.

1586 Background: The U.S. Preventive Services Task Force (USPSTF) recommends that women who meet family history criteria for hereditary breast and ovarian cancer (HBOC) be referred for genetic counseling. However, HBOC genetic testing is under-utilized, particularly among racial/ethnic minorities. We evaluated different methods of family history intake, including a validated family history screener, documentation in the electronic health record (EHR), and a web-based decision aid (DA). Methods: Among women undergoing screening mammography, we administered a validated family history screener to determine eligibility for BRCA genetic testing based upon USPSTF guidelines. We developed a patient-centered DA ( RealRisks) which includes modules on breast cancer risk, collection of detailed family history, and information on HBOC genetic testing. Women who met high-risk criteria for breast cancer were enrolled in an intervention trial to determine whether exposure to RealRisks increases referrals for high-risk consultations. BRCA genetic counseling/testing uptake was assessed by self-report and EHR review. Results: From November 2014 to June 2016, 3077 women completed the family history screener. Median age was 59 years (range, 29-99), including 76% Hispanic, 4% Ashkenazi Jewish, and 60% with a high school education or less. 12% met family history criteria for BRCA genetic testing based upon the family history screener, of which only 5.9% had previously undergone genetic counseling or testing. Sixty high-risk women were enrolled to access RealRisks. When family histories based upon the screener, DA, and EHR were compared, 12 (20%) had discrepancies in number of affected relatives, type of cancer, and age at diagnosis which changed eligibility for BRCA testing. Follow-up is ongoing to determine whether the DA facilitates appropriate referrals for genetic counseling. Conclusions: In a population of predominantly Hispanic and less educated women, a large proportion met USPSTF family history criteria for BRCA testing, but uptake of genetic counseling was low. Developing decision support for accurate family history intake is critical to identifying appropriate candidates for genetic referrals.

The Impact of Mental Illness on Uptake of Genetic Counseling for Hereditary Breast Cancer and Ovarian Cancer in a Multiethnic Cohort of Breast Cancer Patients.

We evaluated whether mental illness is a barrier to genetic counseling for hereditary breast and ovarian cancer (HBOC) in multiethnic breast cancer patients. We conducted a retrospective analysis of 308 women with newly diagnosed breast cancer and eligible for HBOC genetic testing seen in the breast clinic of an academic, urban medical center from 2007 to 2015. Uptake of genetic services and history of mental health disorder (MHD), defined as a psychiatric diagnosis or treatment with an antidepressant, mood stabilizer, anxiolytic, or antipsychotic medication, were ascertained by medical chart review. The mean age at breast cancer diagnosis was 56 years, with 44% non-Hispanic whites, 37% Hispanics, and 15% non-Hispanic blacks. Ninety-nine (32%) women met study criteria for MHD, 73% had a genetics referral, 57% had genetic counseling, and 54% completed BRCA testing. Uptake of genetic counseling services did not differ by race/ethnicity or presence of MHD. In multivariable analysis, younger age at diagnosis, Ashkenazi Jewish heritage, and family history of breast cancer were associated with HBOC genetic counseling. A relatively high proportion of breast cancer patients eligible for HBOC genetic testing were referred to a genetic counselor and referral status did not vary by MHD or race/ethnicity.

Abstract P3-10-06: Genetic testing for HBOC among women with a personal diagnosis of breast cancer in patients with Medicaid as compared to patients with private insurance

Abstract Introduction: National guidelines recommend that women diagnosed with early-onset breast cancer and/or a strong family history receive BRCA1/2 testing to guide treatment decisions. Among newly diagnosed patients, a positive test result will often prompt more aggressive surgical treatment to minimize the risk of second primary cancers. Currently, coverage for genetic counseling and testing for Hereditary Breast and Ovarian Cancer (HBOC) under the Medicaid expansion program of the Affordable Care Act has varied by state, where some states require a copayment for this service. Similarly, there is no mandate to cover risk-reducing surgery for patients found to carry a genetic mutation despite research showing cost-effectiveness. This analysis sought to determine whether genetic testing for HBOC among patients with breast cancer is different for those with Medicaid compared to those with private insurance. Methods: A commercial laboratory database was analyzed for patients with a personal history of breast cancer who underwent testing with a 25-gene hereditary cancer panel from September 2013-February 2016. Patients were eligible for inclusion if they were between ages 18 and 64 at the time of testing and had not undergone previous genetic testing. A total of 17,020 patients with either Medicaid (N=4,313) or one of 5 private payers (N=12,707) were tested during this period. Descriptive statistics, including means for continuous variables and proportions for categorical variables, were calculated. Chi-square tests were used to test associations and differences of positive rates between insurance provider category. Two-tailed p-values are reported, and any p-value less than 0.05 is considered statistically significant. Results: Medicaid patients had a median age of breast cancer diagnosis of 45 compared to 47 for patient with private insurance. Among women with Medicaid insurance, a higher proportion were of African (13.3% vs 6.4%) and Latin American ancestry (16.4% vs 5.3%). The mutation positive rate among patients with Medicaid was 13.0%, which was statistically higher than patients with private insurance (9.5%) (p&amp;lt;0.001). The positive rate was higher among Medicaid patients of all ancestries suggesting that this discrepancy was not due to ancestry difference among the two testing populations. Positive rate by ancestry MedicaidPrivateOverallAfrican80 (13.9%)72 (8.9%)152 (11.0%)Ashkenazi3 (17.6%)20 (15.3%)23 (15.5%)Asian26 (13.3%)40 (7.5%)66 (9.1%)Caucasian201 (12.9%)171 (9.9%)918 (10.4%)Latin American/Caribbean98 (13.8%)65 (9.6%)163 (11.8%)Native American7 (13.7%)9 (7.9%)16 (9.7%)Neareast/Mideast10 (17.9%)8 (9.3%)18 (12.7%)Multiple49 (12.3%)77 (9.0%)126 (10.0%)None Specified85 (11.3%)199 (8.8%)284 (9.4%)Total559 (13.0%)1207 (9.5%)1766 (10.4%) Conclusions: Overall, the positive mutation rate among individuals with Medicaid insurance was higher than those with private insurance, suggesting the testing requirements applied to this population may be more stringent than those applied to the private insurance population. Consistent genetic testing insurance criteria are necessary for all patients to receive care in line with guidelines following a breast cancer diagnosis. Citation Format: Baron P, Johnson-Isidore K, Miller L, Brown K, Kidd J, Saam J, Lancaster J. Genetic testing for HBOC among women with a personal diagnosis of breast cancer in patients with Medicaid as compared to patients with private insurance [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-10-06.

Abstract P2-09-21: HBOC genetic counseling: A genetic counselor-physician partnership model

Abstract Background: In 2003, the American Society of Clinical Oncology (ASCO) issued a policy statement that addressed the oncologist's role in integrating cancer genetic risk assessment and management into clinical practice. ASCO supports access to genetic counseling for patients offered genetic testing and after results disclosure. In 2014, Integrated Genetics (IG) began offering genetic counseling in partnership with OBGYNs and oncologists whose patients have a personal or family history of breast or ovarian cancer. The goal of the program was to provide an easily accessible and comprehensive genetic counseling service for Hereditary Breast and Ovarian Cancer (HBOC) to meet the needs of patients and to support clinicians who currently provide pre- and post-test counseling. Methods: In this study we describe IG's HBOC genetic counseling service and in a retrospective analysis, describe the characteristics of patients referred to the program in 2014. Clinicians were provided a toll free number for patients to call to schedule a genetic counseling session. The scheduling staff facilitated medical record requests and emailed a family history questionnaire. In person or telegenetic counseling (via WebEx) was offered. Telegenetic counseling allowed the patient and genetic counselor to see one another via webcam and view counseling visual aids and relevant medical records. Pedigree analysis and cancer genetic risk assessment were performed and genetic testing options discussed based on National Comprehensive Cancer Network (NCCN) testing criteria. Information discussed at the session, including patient decisions about testing, was documented for the referring physician and patient in the Genetic Counseling Consultation Report. The physician ordered testing and managed patient screening and surveillance. Results: During 2014, 247 counseling sessions were provided to patients from 23 states. All patients had a personal or family history of breast or ovarian cancer and the average age of patients was 44 years (range: 16-85). Sixty four percent (64%) of sessions were done via WebEx and 36% in person. Of the 247 sessions, 198 (80.2%) were for pre-test genetic counseling; of those, 173 (87.4%) met NCCN HBOC genetic testing criteria and genetic testing for BRCA1/2 was offered. Of this group, 70.52% desired testing, 27.75% declined and 1.73% were undecided. The remaining sessions (n=49) included post-test counseling for pathogenic mutations or variants of unknown significance (n=39), and patients who had accepted testing but whose results were pending (n=10). Conclusions: The IG HBOC genetic counseling program extended comprehensive genetic counseling to patients at increased risk for BRCA1/2 mutations who might not otherwise have access to this service. Physicians appropriately selected patients for referral (87% met NCCN testing criteria). The genetic counselors provided cancer genetic risk assessment, time-intensive patient education to facilitate informed decision making, and counseling about the implications of results, including the complexities of variants of unknown significance. This partnership model allowed physicians to retain patient care oversight, including management of screening and surveillance, while leveraging genetic counselor expertise. Citation Format: Oliver JB, Cronister A. HBOC genetic counseling: A genetic counselor-physician partnership model. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-09-21.

Influence of Race/Ethnicity on Genetic Counseling and Testing for Hereditary Breast and Ovarian Cancer

Risk assessment coupled with genetic counseling and testing for the cancer predisposition genes BRCA1 and BRCA2 (BRCA1/2) has become an integral element of comprehensive patient evaluation and cancer risk management in the United States for individuals meeting high-risk criteria for hereditary breast and ovarian cancer (HBOC). For mutation carriers, several options for risk modification have achieved substantial reductions in future cancer risk. However, several recent studies have shown lower rates of BRCA1/2 counseling and testing among minority populations. Here, we explore the role of race/ethnicity in cancer risk assessment, genetic counseling and genetic testing for HBOC and the BRCA1/2 cancer predisposition genes. Barriers to genetic services related to race/ethnicity and underserved populations, including socioeconomic barriers (e.g., time, access, geographic, language/cultural, awareness, cost) and psychosocial barriers (e.g., medical mistrust, perceived disadvantages to genetic services), as well as additional barriers to care once mutation carriers are identified, will be reviewed.

Concerns of Young Women Who are Positive for Brca1 and/or Brca2

The purpose of the study was to examine the experience of predictive genetic testing for hereditary breast and ovarian cancer (HBOC) and to compare experiences of younger women (≤ 35 years old) to the older study cohort (36–60 years old). Grounded theory was used to examine the phenomenon of adults choosing to have predictive genetic testing for HBOC. A sample of 19 women, ten ≤ 35 years old was recruited through community and internet support group announcements. Semi-structured interviews were conducted in-person, by telephone or E-mail: according to participant preference. Young women’s experiences were different particularly around concerns about: (i) career plans, (ii) reproduction, and (iii) intimate relationships. Other concerns not specific to young women but also described included: (i) family relationships, (ii) fears of personal mortality, (iii) life and health insurance, and (iv) health information needs. A commonly voiced experience specific to the young adult age group was feeling ‘out-of-place’ in the oncology clinics and support groups which participants perceived as being focused on concerns of older women. Further study may clarify the extent and nature of informational, emotional, social and decision support needs that are unique to this young adult population.