Uptake Of BRCA Testing Research Articles

Leveraging an Informatics Approach to Identify an Unmet Clinical Need for BRCA1/2 Testing Among Patients With Ovarian Cancer.

Although BRCA1/2 testing in ovarian cancer improves outcomes, it is vastly underutilized. Scalable approaches are urgently needed to improve genomically guided care. We developed a Natural Language Processing (NLP) pipeline to extract electronic medical record information to identify recipients of BRCA testing. We applied the NLP pipeline to assess testing status in 308 patients with ovarian cancer receiving care at a National Cancer Institute Comprehensive Cancer Center (main campus [MC] and five affiliated clinical network sites [CNS]) from 2017 to 2019. We compared characteristics between (1) patients who had/had not received testing and (2) testing utilization by site. We found high uptake of BRCA testing (approximately 78%) from 2017 to 2019 with no significant differences between the MC and CNS. We observed an increase in testing over time (67%-85%), higher uptake of testing among younger patients (mean age tested = 61 years v untested = 65 years, P = .01), and higher testing among Hispanic (84%) compared with White, Non-Hispanic (78%), and Asian (75%) patients (P = .006). Documentation of referral for an internal genetics consultation for BRCA pathogenic variant carriers was higher at the MC compared with the CNS (94% v 31%). We were able to successfully use a novel NLP pipeline to assess use of BRCA testing among patients with ovarian cancer. Despite relatively high levels of BRCA testing at our institution, 22% of patients had no documentation of genetic testing and documentation of referral to genetics among BRCA carriers in the CNS was low. Given success of the NLP pipeline, such an informatics-based approach holds promise as a scalable solution to identify gaps in genetic testing to ensure optimal treatment interventions in a timely manner.

Jewish cultural and religious factors and uptake of population-based BRCA testing across denominations: a cohort study.

To evaluate the association of Jewish cultural and religious identity and denominational affiliation with interest in, intention to undertake and uptake of population-based BRCA (Breast Cancer Gene)-testing. Cohort-study set within recruitment to GCaPPS-trial (ISRCTN73338115). London Ashkenazi-Jewish (AJ) population. AJ men and women, >18 years. Participants were self-referred, and attended recruitment clinics (clusters) for pre-test counselling. Subsequently consenting individuals underwent BRCA testing. Participants self-identified to one Jewish denomination: Conservative/Liberal/Reform/Traditional/Orthodox/Unaffiliated. Validated scales measured Jewish Cultural-Identity (JI) and Jewish Religious-identity (JR). Four-item Likert-scales analysed initial 'interest' and 'intention to test' pre-counselling. Item-Response-Theory and graded-response models, modelled responses to JI and JR scales. Ordered/multinomial logistic regression modelling evaluated association of JI-scale, JR-scale and Jewish Denominational affiliation on interest, intention and uptake of BRCA testing. Interest, intention, uptake of BRCA testing. In all, 935 AJ women/men of mean age = 53.8 (S.D = 15.02) years, received pre-test education and counselling through 256 recruitment clinic clusters (median cluster size = 3). Denominational affiliations included Conservative/Masorti = 91 (10.2%); Liberal = 82 (9.2%), Reform = 135 (15.1%), Traditional = 212 (23.7%), Orthodox = 239 (26.7%); and Unaffiliated/Non-practising = 135 (15.1%). Overall BRCA testing uptake was 88%. Pre-counselling, 96% expressed interest and 60% intention to test. JI and JR scores were highest for Orthodox, followed by Conservative/Masorti, Traditional, Reform, Liberal and Unaffiliated Jewish denominations. Regression modelling showed no significant association between overall Jewish Cultural or Religious Identity with either interest, intention or uptake of BRCA testing. Interest, intention and uptake of BRCA testing was not significantly associated with denominational affiliation. Jewish religious/cultural identity and denominational affiliation do not appear to influence interest, intention or uptake of population-based BRCA testing. BRCA testing was robust across all Jewish denominations. Jewish cultural/religious factors do not affect BRCA testing, with robust uptake seen across all denominational affiliations.

Attitude towards and factors affecting uptake of population-based BRCA testing in the Ashkenazi Jewish population: a cohort study.

To evaluate factors affecting unselected population-based BRCA testing in Ashkenazi Jews (AJ). Cohort-study set within recruitment to the GCaPPS trial (ISRCTN73338115). North London AJ population. Ashkenazi Jews women/men>18 years, recruited through self-referral. Ashkenazi Jews women/men underwent pre-test counselling for BRCA testing through recruitment clinics (clusters). Consenting individuals provided blood samples for BRCA testing. Data were collected on socio-demographic/family history/knowledge/psychological well-being along with benefits/risks/cultural influences (18-item questionnaire measuring 'attitude'). Four-item Likert-scales analysed initial 'interest' and 'intention-to-test' pre-counselling. Uni- and multivariable logistic regression models evaluated factors affecting uptake/interest/intention to undergo BRCA testing. Statistical inference was based on cluster robust standard errors and joint Wald tests for significance. Item-Response Theory and graded-response models modelled responses to 18-item questionnaire. Interest, intention, uptake, attitude towards BRCA testing. A total of 935 individuals (women=67%/men=33%; mean age=53.8 (SD=15.02) years) underwent pre-test genetic-counselling. During the pre-counselling, 96% expressed interest in and 60% indicated a clear intention to undergo BRCA testing. Subsequently, 88% opted for BRCA testing. BRCA-related knowledge (P=0.013) and degree-level education (P=0.01) were positively and negatively (respectively) associated with intention-to-test. Being married/cohabiting had four-fold higher odds for BRCA testing uptake (P=0.009). Perceived benefits were associated with higher pre-counselling odds for interest in and intention to undergo BRCA testing. Reduced uncertainty/reassurance were the most important factors contributing to decision-making. Increased importance/concern towards risks/limitations (confidentiality/insurance/emotional impact/inability to prevent cancer/marriage ability/ethnic focus/stigmatisation) were significantly associated with lower odds of uptake of BRCA testing, and discriminated between acceptors and decliners. Male gender/degree-level education (P=0.001) had weaker correlations, whereas having children showed stronger (P=0.005) associations with attitudes towards BRCA testing. BRCA testing in the AJ population has high acceptability. Pre-test counselling increases awareness of disadvantages/limitations of BRCA testing, influencing final cost-benefit perception and decision-making on undergoing testing. BRCA testing in Ashkenazi Jews has high acceptability and uptake. Pre-test counselling facilitates informed decision-making.

PCN254 - TRENDS IN BRCA TESTING OVER TIME AND SOCIOECONOMIC DEPRIVATION

BRCA1&2 (BRCA) testing received much publicity following Angelina Jolie’s editorial ‘My Medical Choice’ in the New York Times on the 14th May 2013. In addition, in the UK, guidelines were updated by NICE (clinical guidance CG164) on the 25th June 2013. We analysed the effects of these two events on uptake of BRCA1 and BRCA2 testing in the area covered by Cheshire and Merseyside Regional Genetic Service, and whether this was affected by socioeconomic deprivation. A database was collated using routinely collected hospital data for patients who received hereditary breast and ovarian cancer (HBOC) BRCA testing. A total of 1393 patients received BRCA testing. A natural experimental approach was undertaken using segmented linear regression to estimate changes in the level and trend of BRCA testing following the publication of both the Jolie’s editorial and NICE CG164. Regression coefficients were used to calculate average change in rates, adjusted for prior level and trend. The Index of Multiple Deprivation (IMD) of patients from areas who received BRCA testing to those of the catchment population were compared. The month following the publication of Jolie’s editorial and NICE CG164, BRCA testing increased by approximately 84% (P=0.006). Between April 2010 and March 2017, testing rates increased 11-fold from 0.14 to 1.52 tests/100,000 per month. The odds of receiving BRCA testing were higher for patients from socioeconomically advantaged areas pre-publication (OR 1.21 95% CI 0.99-1.48, P=0.06) although this was not significant. After publication the odds were significantly higher for patients from advantaged areas compared with disadvantaged areas (OR 1.18 95% CI 1.08-1.29, P=0.0002). Our study found that BRCA testing uptake increased following the publication of Jolie’s editorial and NICE CG164. However, uptake was lower in more deprived areas. This inequity should be further investigated, and consideration given to targeted care within areas of greater socioeconomic deprivation.

Abstract P5-23-01: Clinical and biological characterization of male breast cancer (BC) EORTC 10085/TBCRC 029/BOOG 2013-02/BIG 2-07: Baseline results from the prospective registry

Abstract BACKGROUND: Through the International Male Breast Cancer Program, a prospective registry for male BC was created with the goals of evaluating 1) the clinical and biological features of this disease and 2) assessing feasibility of a prospective therapeutic clinical trial. METHODS: All men, with any stage histologically proven invasive breast cancer, age 3 18 years, and newly presenting at the participating institutions (within 3 months prior) were eligible. Patients were enrolled for 30 months after activation of the first center, through February 2017. Per the study design, if <100 men enrolled, the study would be considered a failure and therapeutic trials would not be pursued through this network. Epidemiologic data, staging, pathologic features, and BRCA status were collected. Treatment and outcome data collection is ongoing. Optional collection of FFPE tumor samples, blood, and QOL were performed in the US, the Netherlands, and Latin America. Clinical database lock for this report was May 30, 2017. We currently report patient and disease characteristics and will update with patterns of treatment for the presentation. Outcomes and biological samples will be analyzed in the future. RESULTS: 557 patients were enrolled: 75% in Europe, 20% in United States, 5% in other countries. 6.3% of patients had missing forms. Median age was 67 years (range 26-92). 93% were diagnosed 2010-2017. Among patients with complete data, 79% presented with a breast mass. 88% were M0 and 12% M1. Among M0 patients: 47%, 39%, 2%, and 11% had T1, T2, T3, and T4 disease respectively; 52% were N0. Overall, 98% had ER+ disease and 11% had HER2+ cancer. 14% had grade 1, 56% had grade 2, and 30% had grade 3 tumors. Among 112 men who underwent BRCA1 testing, 1 was positive. Among 118 men who had BRCA2 testing, 18 (15%) were positive. 21% of men had prior or concurrent malignancies, with the following most common sites: prostate, non-melanoma skin, colorectal, and melanoma. The prevalence of previously identified possible risk factors for male breast cancer were: overweight/obesity (72%), former/current smoker (51%), current alcohol 31 drink daily (41%), family history of breast cancer (35%), gynecomastia (16%), history radiation exposure (8%), use of anti-androgens (1%), and use of estrogens (1%). CONCLUSION: Through an international collaborative effort, we were able to prospectively accrue 557 patients to a male breast cancer registry. These results demonstrate feasibility of pursuing a therapeutic clinical trial in men with breast cancer. In addition, this study shows the relatively low uptake of BRCA testing, high rates of concurrent/prior malignancy, and the rates of potentially modifiable risk factors in this patient population. Funding from Breast Cancer Research Foundation, Susan G. Komen, Dutch Pink Ribbon Foundation, Swedish Breast Cancer Association (BRO) and EBCC Council. Citation Format: Giordano SH, Schröder CP, Poncet C, van Leeuwen-Stok E, Linderholm B, Abreu MH, Rubio I, Van Poznak C, Morganstern D, Cameron D, Vleugel MM, Smilde TJ, Bozovic-Spasojevic I, Korde L, Russell NS, den Hoed IDM, Honkoop AH, van der Velden AWG, van 't Riet M, Dijkstra N, Bogler O, Goulioti T, Hilsenbeck S, Ruddy KJ, Wolff A, van Deurzen CHM, Martens J, Bartlett JMS, Aalders K, Tryfonidis K, Cardoso F. Clinical and biological characterization of male breast cancer (BC) EORTC 10085/TBCRC 029/BOOG 2013-02/BIG 2-07: Baseline results from the prospective registry [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-23-01.

Assessment of BRCA testing uptake in ovarian cancer patients during the implementation of an oncologist-led genetic counseling model at an urban and suburban teaching hospital.

1589 Background: BRCA testing has become an integral component of ovarian cancer management; however, low testing uptake remains an obstacle. This study evaluated the impact of an oncologist-led counseling and testing model on BRCA testing uptake. Methods: The ENGAGE study (NCT02406235) is a prospective study of an oncologist-led BRCA counseling and testing model in patients with epithelial ovarian, primary peritoneal and fallopian tube cancer (EOC). The United States lead accruing gynecologic oncology sites were Montefiore, an urban academic medical center; and Winthrop, a suburban teaching hospital. Oncologists were trained in BRCA counseling prior to site activation, and directly submitted patients’ samples for BRCA testing. Prior to the ENGAGE study, EOC patients were referred to genetics professionals for counseling and testing. We determined the number of BRCA tests performed, and simple descriptive statistics were used to summarize the data. Results: A combined total of 141 EOC patients underwent BRCA testing during the 20 consecutive months analyzed. In the 10 months pre-ENGAGE, 8 Montefiore patients had BRCA testing, all submitted through the genetics division. Nineteen Winthrop patients had BRCA testing, 16 from their oncologist’s office and 3 from an external genetics office. During the 10-month ENGAGE trial, 64 Montefiore patients and 50 Winthrop patients had BRCA testing. This represents a four-fold increase in BRCA testing uptake, with 114 patients tested during ENGAGE versus 27 patients tested pre-ENGAGE. Of these 114, 99 had BRCA counseling and testing through their oncologist’s office. Conclusions: Implementation of an oncologist-led genetic counseling and testing model was associated with increased BRCA testing among ovarian cancer patients in both the urban and suburban hospitals. Increased BRCA testing could be related to increased patient convenience and standardized training of the clinical team. These findings may guide other institutions as they implement streamlined genetic counseling and testing protocols.

Abstract A34: How important is comprehensive rearrangement testing for BRCA mutations in African American women with early-onset breast cancer?

Abstract Background: Young Black women are disproportionately afflicted with breast cancer, a proportion of which may be due to BRCA1 and BRCA2 (BRCA) gene mutations. Deleterious mutations in the BRCA genes include those identified by sequencing technology as well as large genomic rearrangements that are found with different technologies (i.e., multiplex ligation-dependent probe amplification (MLPA)). The sole provider of clinical BRCA genetic testing in the United States is Myriad Genetics Laboratories, the company which owns the patent on these genes. When BRCA testing is ordered through this company, the standard test is called ‘Comprehensive BRCAnalysis’, which includes BRCA sequencing and testing for five rearrangements in BRCA1. In addition, testing for large rearrangements has been available since 2006, but is ordered and billed as a separate test from Comprehensive BRCAnalysis (at a cost of $700, often as an out-of-pocket expense). Objectives: In a cancer registry-based sample of Black women with early onset breast cancer, we evaluated prevalence of: 1) BRCA mutations; and 2) individuals who had BRCA testing (+counseling) predating study enrollment. Methods: Black women diagnosed with invasive breast cancer < age 50 in 2009-2010 were recruited through the Florida Cancer Registry utilizing state-mandated recruitment methods. Participants completed genetic counseling and a comprehensive risk factor questionnaire which included uptake of clinical BRCA testing pre-dating study enrollment. All participants consented to medical record release, including release of prior genetic test results. Saliva specimens were collected and BRCA testing was performed on all individuals through full gene sequencing and comprehensive rearrangement testing. Results: Of the first 48 participants in whom results of genetic testing are currently available through the study, two mutations in the BRCA genes were detected. Both mutations were identified in women who had undergone comprehensive BRCAnalysis pre-dating study enrollment. This included one participant identified to have a deleterious BRCA2 mutation through prior clinical testing (BRCA2 exon11 5844del5), in whom the same mutation was detected through the study. The second mutation was identified through comprehensive rearrangement testing (BRCA1 delExon8) in a woman who had previously had clinical BRCA testing during her breast cancer treatment in whom no mutation was detected through ‘Comprehensive BRCAnalaysis’. Of note, 15 women overall (31.3%) had clinical BRCA testing pre-dating study enrollment, which included both women identified as mutation carriers. Conclusions: Our findings suggest that it is critical to offer comprehensive rearrangement testing as part of BRCA testing in African American women, as one of the two mutations identified in our study was only identified through MLPA. Furthermore, in contrast to prior publications which suggest low uptake of BRCA testing in African American women, our results suggest reasonable uptake of BRCA testing in a registry-based sample of African American women with rates comparable to that previously reported in White women. Citation Format: Tuya PalDevon Bonner, Mohammad Akbari, Steven Narod, Susan Vadaparampil. How important is comprehensive rearrangement testing for BRCA mutations in African American women with early-onset breast cancer? [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr A34.

Sharing BRCA results: are there disparities?.

Abstract Abstract #1101 Background: BRCA is a unique breast cancer biomarker; it defines risk not only for an individual, but also for a family. Little is known about sharing BRCA results with relatives. This study aims to determine which relatives are told of BRCA results and which relatives pursue BRCA testing. This study also explores whether patient and relative characteristics can account for differences in sharing BRCA results and BRCA testing of relatives.
 Methods: As part of the UCSF Cancer Risk Program Cohort, all women who receive genetic counseling and BRCA testing at the UCSF/Mt. Zion Comprehensive Cancer Center (CCC) and at San Francisco General Hospital (SFGH) are sent a survey regarding their health habits and their genetic testing experience. Women surveyed are asked: whether they have shared BRCA results; if so, with whom; and whether other family members have pursued BRCA testing. Patient-level variables examined include: cancer status, hospital site, and BRCA results. Relative-level variables examined include: gender and degree of relationship (first- or second-degree).
 Results: Over 80% of women surveyed have responded to date (n = 151). Overall, 95% report sharing BRCA results with at least one relative, and 41% indicate that other relatives have received BRCA testing. Tables 1 and 2 show rates of telling relatives and of BRCA testing in relatives based on patient and relative characteristics. Although the proportion of BRCA carriers is similar at both sites (22% at the CCC and 20% at SFGH), relatives of SFGH patients are significantly less likely to pursue BRCA testing (p=0.001).
 
 
 
 Conclusions: After BRCA testing, women are less likely to share results with male and second-degree relatives. The proportion of BRCA carriers is similar at SFGH and at the CCC. Rates of telling relatives of BRCA results are also similar at both sites. A large and significant disparity exists, however, in BRCA testing of relatives of women from SFGH (8% from SFGH vs. 47% from the CCC, p = 0.001). Future research will examine the reasons for low uptake of BRCA testing in this population, barriers to BRCA testing, and potential interventions. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1101.

BRCA testing uptake and participation in ovarian cancer prevention in women at risk for an inherited ovarian cancer susceptibility

The aim of this study was to assess BRCA testing uptake in women with a family history suggestive of an inherited ovarian cancer risk, and to evaluate their participation in preventive measures including bilateral salpingo-oophorectomy (BSO), screening with transvaginal ultrasound (TVUS) and serum CA125, and chemoprevention with oral contraceptives (OCPs). From January 1998 through June 1999, 112 women received genetic risk assessment and counseling regarding a possible inherited susceptibility to ovarian and related cancers. 62% were Jewish and 42% had a history of breast cancer. Of these 112 women, 72% elected to participate in BRCA testing; deleterious mutations were identified in 22% (18/81). Jewish patients represented 79% of the subjects who chose to undergo testing, and included 93% (64/69) of all Jewish patients. Only 40% (17/43) of non-Jewish patients chose testing. Almost all (89%) of the 18 deleterious mutations identified were in Jewish patients; 25% (16/64) of Jews who were tested had deleterious mutations compared to only 12% (2/17) of non-Jews. Jewish patients were more likely than non-Jews to have a personal history of breast cancer, 52% (33/69) compared to 26% (11/43), p<0.03. Follow-up regarding participation in preventive services was available for 18 of 22 women seen in the past 3 years who had both intact ovaries and deleterious BRCA mutations. 10 of the 18 women underwent BSO, and 7 are participating in TVUS and CA125 and/or are taking OCPs for ovarian cancer prevention. Only 3 women had been participating in ovarian cancer screening prior to their genetic consultation, and none were taking OCPs for chemoprevention. Age and personal history of breast cancer did not distinguish between those who did and did not elect BSO. 9 of the 13 Jewish women (69%) with a BRCA mutation had BSO, as did 1 of 2 non-Jewish women. These preliminary data suggest that women with BRCA mutations participate in appropriate preventive strategies for ovarian cancer; most choosing prophylactic BSO. Jewish patients were more likely to undergo BRCA testing than non-Jewish patients; this might be due to the increased mutation detection rate and reduced cost of testing. Thus at this time, genetic risk assessment and testing appears to be most beneficial for Jewish women at risk for an inherited susceptibility to ovarian cancer.