Screening for Individuals at Risk for Hereditary Breast and Ovarian Cancer: A Statewide Initiative, Georgia, 2012-2020.

Georgia implemented a statewide family history screening program for hereditary breast and ovarian cancer. From November 2012 through December 2020, 29 090 individuals were screened, 16 679 of whom (57.3%) self-identified as a racial/ethnic minority. Of the 4% (1172/29 090) of individuals who screened as high risk, more than half underwent genetic consultation (793/1172; 67.7%) and testing (416/589; 70.6%). Compared with White women, Black and Hispanic women had higher uptake rates of genetic consultation. Public health settings serving racial minorities are well suited to address disparities in genetic service access. (Am J Public Health. 2022;112(9):1249-1252. https://doi.org/10.2105/AJPH.2022.306932).

Hereditary Breast and Ovarian Cancer: An Updated Primer for OB/GYNs.

This article provides an update on hereditary breast and ovarian cancer syndrome (HBOC) associated with pathogenic variants (PVs) in BRCA1/2. While many new genes have been identified and are included in testing panels, HBOC will serve as the primary example to illustrate the main concepts involved in genetic testing and management for hereditary breast and/or ovarian cancer We provide practical information regarding collecting a family history, cancer risk assessment, genetic testing and result interpretation, BRCA-associated cancer prognosis and treatment, screening recommendations, and prevention strategies. We also introduce implications of more recently identified cancer genes, polygenic risk scores (PRSs), and tumor genomic profiling. Evidence-based management strategies have been shown to reduce cancer incidence and improve survival in HBOC and other high penetrance syndromes. Obstetricians and gynecologists familiar with these concepts can identify and improve the quality of care for women and families impacted by hereditary breast and/or ovarian cancer.

Do Women who Receive a Negative BRCA1/2 Risk Result Understand the Implications for Breast Cancer Risk?

BACKGROUND/AIMS: National guidelines endorse using evidence-based tools to identify those at risk for hereditary breast and ovarian cancer (HBOC). This study aimed to evaluate whether women deemed not to be at increased risk of being a BRCA mutation carrier; the majority of those screened, recall, understand and accept the implications of these results for breast cancer risk. METHODS: We conducted an online survey with women (n = 148) who screened negative on a brief HBOC screener. RESULTS: While women tended to accept HBOC screener as accurate (range 9-45; mean 32, SD 5.0), less than half (43%) accurately recalled their result. Only 52% understood that they were at low risk of carrying a mutation, and just 34% correctly understood their breast cancer risk. African American women were less likely to recall (33 vs. 53% respectively, OR 0.5, p = 0.03), understand (42 vs. 63% respectively, OR 0.4, p = 0.02), and accept (mean 31 vs. 33 respectively, ß -2.1, p = 0.02) the result compared to Whites. CONCLUSIONS: Our findings show that those at low risk of carrying a BRCA1/2 mutation had limited understanding of the distinction between mutation risk and breast cancer risk. Theory-based communication strategies are needed to increase the understanding of the implications of being at low risk for hereditary cancers.

Willingness to decrease mammogram frequency among women at low risk for hereditary breast cancer.

This study aimed to assess women's willingness to alter mammogram frequency based on their low risk for HBOC, and to examine if cognitive and emotional factors are associated with women's inclination to decrease mammogram frequency. We conducted an online survey with women (N = 124) who were unlikely to have a BRCA mutation and at average population risk for breast cancer based on family history. Most women were either white (50%) or African American (38%) and were 50 years or older (74%). One-third of women (32%) were willing to decrease mammogram frequency (as consistent with the USPSTF guideline), 42% reported being unwilling and 26% were unsure. Multivariate logistic regression showed that feeling worried about breast cancer (Adjust OR = 0.33, p = 0.01), greater genetic risk knowledge (Adjust OR = 0.74, p = 0.047), and more frequent past mammogram screening (Adjust OR = 0.13, p = 0.001) were associated with being less willing to decrease screening frequency. Findings suggest that emerging genomics-informed medical guidelines may not be accepted by many patients when the recommendations go against what is considered standard practice. Further study of the interplay between emotion- and cognition-based processing of the HBOC screen result will be important for strategizing communication interventions aimed at realizing the potential of precision public health.

Infrastructure and Educational Needs of Newborn Screening Short-Term Follow-Up Programs within the Southeast Regional Newborn Screening & Genetics Collaborative: A Pilot Survey.

Newborn screening (NBS) follow-up protocols vary significantly by state, and there is a need to better understand the infrastructure and communication flow of NBS programs. In addition, assessment of the educational needs of families and providers with regard to the implications of NBS results is required to inform the development of appropriate informational resources and training opportunities. To begin to address these issues, we administered a web-based survey to state NBS coordinators within the Southeast Regional Newborn Screening & Genetics Collaborative (SERC). Fourteen coordinators responded to the survey, including at least one from each of the 10 SERC states/territories. Over one-third of respondents had never received formal training regarding the metabolic conditions identified on NBS. Most communicated results via telephone or fax, though two centers indicated use of a web-based platform. Only two programs were involved in directly reporting results to the family. Four programs reported a long-term follow-up protocol. Deficits were noted for primary care provider (PCP) knowledge of metabolic disorders identified on NBS, and how to inform parents of abnormal results. Close to half indicated that the adequacy of the number of genetic counselors, dietitians, and medical/biochemical geneticists was minimal to insufficient. Respondents uniformly recognized the importance of providing additional educational and informational resources in multiple categories to NBS staff, PCPs, and families.

Characteristics associated with genetic counseling referral and BRCA1/2 testing among women in a large integrated health system.

BACKGROUND: Evidence shows underutilization of cancer genetics services. To explore the reasons behind this underutilization, this study evaluated characteristics of women who were referred for genetic counseling and/or had undergone BRCA1/2 testing. METHODS: An ovarian cancer risk perception study stratified 16,720 eligible women from the Henry Ford Health System into average-, elevated-, and high-risk groups based on family history. We randomly selected 3,307 subjects and interviewed 2,524 of them (76.3% response rate). RESULTS: Among the average-, elevated-, and high-risk groups, 2.3, 10.1, and 20.2%, respectively, reported genetic counseling referrals, and 0.8, 3.3, and 9.5%, respectively, reported having undergone BRCA testing. Personal breast cancer history, high risk, and perceived ovarian cancer risk were associated with both referral and testing. Discussion of family history with a doctor predicted counseling referral, whereas belief that family history influenced risk was the strongest BRCA testing predictor. Women perceiving their cancer risk as much higher than other women their age were twice as likely (95% confidence interval: 2.0-9.6) to report genetic counseling referral. CONCLUSION: In a health system with ready access to cancer genetic counseling and BRCA testing, women who were at high risk underutilized these services. There were strong associations between perceived ovarian cancer risk and genetic counseling referral, and between a belief that family history influenced risk and BRCA testing.

Implementing a screening tool for identifying patients at risk for hereditary breast and ovarian cancer: a statewide initiative.

BACKGROUND: The Georgia Breast Cancer Genomic Health Consortium is a partnership created with funding from the Centers for Disease Control and Prevention (CDC) to the Georgia Department of Public Health to reduce cancer disparities among high-risk minority women. The project addresses young women at increased risk for hereditary breast and ovarian cancer (HBOC) syndrome through outreach efforts. METHODS: The consortium provides education and collects surveillance data using the breast cancer genetics referral screening tool (B-RST) available at www.BreastCancerGeneScreen.org . The HBOC educational protocol was presented to 73 staff in 6 public health centers. Staff used the tool during the collection of medical history. Further family history assessments and testing for mutations in the BRCA1/2 genes were facilitated if appropriate. RESULTS: Data was collected from November 2012 through December 2013, including 2,159 screened women. The majority of patients identified as black/African American and were 18-49 years old. Also, 6.0 % (n = 130) had positive screens, and 60.9 % (n = 67) of the 110 patients who agreed to be contacted provided a detailed family history. A total of 47 patients (42.7 %) met National Comprehensive Cancer Network guidelines when family history was clarified. Fourteen (12.7 %) underwent genetic testing; 1 patient was positive for a BRCA2 mutation, and 1 patient was found to carry a variant of uncertain significance. CONCLUSIONS: The introduction of genomics practice within public health departments has provided access to comprehensive cancer care for uninsured individuals. The successful implementation of the B-RST into public health centers demonstrates the opportunity for integration of HBOC screening into primary care practices.

Hereditary breast/ovarian cancer syndrome: a primer for obstetricians/gynecologists.

An understanding of the diagnosis and clinical management of hereditary breast and ovarian cancer syndrome (HBOC) is essential for obstetricians/gynecologists. This article provides practical information regarding collecting a family history, cancer risk assessment and genetic testing, BRCA-associated cancer prognosis and treatment, screening recommendations, and prevention strategies. Through appropriate cancer risk assessment, women with BRCA1/2 mutations can be identified, and screening and prevention strategies can be used before a diagnosis of cancer occurs. Women's health providers with a strong working knowledge of HBOC are able to improve the quality of care for women and families impacted by BRCA1/2 mutations.

Recruiting women for a study on perceived risk of cancer: influence of survey topic salience and early versus late response.

INTRODUCTION: Understanding the characteristics of early and late survey responders has implications for recruitment efforts and for informing potential response bias. The main objective of this analysis was to examine survey responder status (ie, early vs late response) by sociodemographic characteristics and by salience of study variables among respondents. METHODS: We analyzed data from a survey on family cancer history and perceived cancer risk among women at a large managed health-care organization. For baseline and 12-month follow-up surveys, we defined early versus late responder status according to the 95th percentile of the number of days it took to obtain completed interviews. RESULTS: We found no significant associations between responder status and sociodemographic characteristics at baseline or follow-up. At baseline, early responders were significantly more likely than late responders to have a personal history of breast cancer (5.2% vs 3.4%, P = .04) and to have been referred for genetic counseling (4.6% vs 2.0%, P = .004). The association between personal history of breast cancer and responder status persisted at follow-up; only 3.5% of late responders at baseline were also late responders at follow-up. Follow-up survey nonresponse rates did not vary by baseline responder status. CONCLUSION: Survey topic salience is associated with early response and is important for recruitment. However, once recruited, late responders do not remain late responders at follow-up, suggesting that extra efforts made to recruit late responders are worthwhile. Health-related agencies that conduct surveys should consider survey salience in survey administration and recruitment strategies.

Prevalence and healthcare actions of women in a large health system with a family history meeting the 2005 USPSTF recommendation for BRCA genetic counseling referral.

BACKGROUND: In 2005, the United States Preventive Services Task Force (USPSTF) released guidelines which outlined specific family history patterns associated with an increased risk for BRCA1/2 mutations, and recommended at-risk individuals be referred for genetic counseling and evaluation for BRCA testing. The purpose of this study was to assess the prevalence of individuals with a USPSTF increased-risk family history pattern, the frequency with which specific patterns were met, and resulting healthcare actions among women from the Henry Ford Health System. METHODS: As part of a study evaluating ovarian cancer risk perception and screening, 2,524 randomly selected participants completed a detailed interview (response rate 76%) from an initial eligible cohort of 16,720 women. RESULTS: Approximately 6% of participants had a family history fulfilling one or more of the USPSTF patterns. Although 90% of these women had shared their family history with their provider, less than 20% had been referred for genetic counseling and only 8% had undergone genetic testing. Caucasian women with higher income and education levels were more likely to receive referrals. Among the 95 participants in the total study cohort who reported BRCA testing, 78% did not have a family history that met one of the USPSTF patterns. CONCLUSIONS: These results suggest a higher prevalence of women with an increased-risk family history than originally predicted by the USPSTF, and lack of provider recognition and referral for genetic services. IMPACT: Improvements in healthcare infrastructure and clinician education will be required to realize population level benefits from BRCA genetic counseling and testing.

Direct-to-consumer personal genome testing and cancer risk prediction.

The last several years has witnessed an explosion in genomics, with the advent of genome-wide association studies revealing hundreds of DNA variants significantly associated with most common diseases, including cancer. On the heels of these scientific advances came the direct-to-consumer (DTC) genetic testing industry. Genome-wide scans for disease have been marketed and sold directly to the public, without the involvement of a health care provider. Unlike genetic testing for mutations in known hereditary cancer susceptibility genes such as BRCA1/2, these genomic profiles examine DNA variants, which typically have a minimal risk impact, and account for only a fraction of the heritable component of cancer. Furthermore, risk information provided to consumers does not account for family history or other known risk factors. The clinical validity and utility of personal genome scans for disease risk prediction remain for the most part unestablished, although some argue lack of evidence of harm and the possibility that positive impacts on health behaviors or genetic awareness may result from consumer use. The DTC genetic testing industry has sparked significant controversy not only among the scientific community, but also among professional societies and government agencies.In this review, we present some of the history and methodological considerations of DTC genomic profiling, with a focus on cancer risk prediction. The literature regarding consumer awareness and utilization is explored, including understanding, expectations, and behavioral and psychological responses to DTC genomic risk prediction. Primary care provider and genetic professional knowledge and perceptions of DTC genomic profiling are also addressed. Ethical and scientific controversy surrounding the DTC genetic testing industry is presented, along with policy recommendations, regulatory actions, and the changing landscape of the DTC genetic testing market in response. Although our understanding of the human genome holds much promise in the realm of cancer prevention and treatment, DTC genomic profiling for cancer risk prediction is unlikely in its current form to have any significant impact on the health of the public. Time will tell if the next venture in genomic medicine, whole genome sequencing, will be accompanied by the translational research and emphasis on public/provider education required to ensure its successful application toward reducing the burden of cancer at a population level.

Implementing screening for Lynch syndrome among patients with newly diagnosed colorectal cancer: summary of a public health/clinical collaborative meeting.

Lynch syndrome is the most common cause of inherited colorectal cancer, accounting for approximately 3% of all colorectal cancer cases in the United States. In 2009, an evidence-based review process conducted by the independent Evaluation of Genomic Applications in Practice and Prevention Working Group resulted in a recommendation to offer genetic testing for Lynch syndrome to all individuals with newly diagnosed colorectal cancer, with the intent of reducing morbidity and mortality in family members. To explore issues surrounding implementation of this recommendation, the Centers for Disease Control and Prevention convened a multidisciplinary working group meeting in September 2010. This article reviews background information regarding screening for Lynch syndrome and summarizes existing clinical paradigms, potential implementation strategies, and conclusions which emerged from the meeting. It was recognized that widespread implementation will present substantial challenges, and additional data from pilot studies will be needed. However, evidence of feasibility and population health benefits and the advantages of considering a public health approach were acknowledged. Lynch syndrome can potentially serve as a model to facilitate the development and implementation of population-level programs for evidence-based genomic medicine applications involving follow-up testing of at-risk relatives. Such endeavors will require multilevel and multidisciplinary approaches building on collaborative public health and clinical partnerships.

Awareness and utilization of BRCA1/2 testing among U.S. primary care physicians.

BACKGROUND: Testing for mutations in the breast and ovarian cancer susceptibility genes BRCA1 and BRCA2 (BRCA) has been commercially available since 1996. PURPOSE: This study sought to determine, among U.S. primary care physicians, the level of awareness and utilization of BRCA testing and the 2005 U.S. Preventive Services Task Force (USPSTF) recommendations. METHODS: In 2009, data were analyzed on 1500 physician respondents to the 2007 DocStyles national survey (515 family practitioners, 485 internists, 250 pediatricians, and 250 obstetricians/gynecologists). RESULTS: Overall, 87% of physicians were aware of BRCA testing, and 25% reported having ordered testing for at least one patient in the past year. Ordering tests was most prevalent among obstetricians/gynecologists in practice for more than 10 years, with more affluent patients. Physicians were asked to select indications for BRCA testing from seven different clinical scenarios representing increased (4) or low-risk (3) situations consistent with the USPSTF guidelines. Among ordering physicians (pediatricians excluded), 45% chose at least one low-risk scenario as an indication for BRCA testing. Only 19% correctly selected all of the increased-risk and none of the low-risk scenarios. CONCLUSIONS: A substantial majority of primary care physicians are aware of BRCA testing and many report having ordered at least one test within the past year. A minority, however, appear to consistently recognize the family history patterns identified by the USPSTF as appropriate indications for BRCA evaluation. These results suggest the need to improve providers' knowledge about existing recommendations-particularly in this era of increased BRCA direct-to-consumer marketing.

Evaluation of a breast/ovarian cancer genetics referral screening tool in a mammography population.

PURPOSE: Simple screening tools are needed to facilitate the appropriate referral of patients for genetic counseling and testing for BRCA1/2 mutations. This study evaluated the reliability and accuracy of a "referral screening tool" designed for rapid identification of individuals at potential hereditary risk for breast/ovarian cancer. METHODS: The referral screening tool was administered to 2464 unselected women undergoing screening mammography. Detailed four-generation cancer pedigrees were collected by telephone interview on a random subset of 296 women. The pedigrees were analyzed using four established hereditary risk models (BRCAPRO, Myriad II, BOADICEA, FHAT), with a > or =10% BRCA1/2 mutation probability or a FHAT score of > or =10 as the definition of "high risk." RESULTS: The referral screening tool identified 6.2% of subjects as screen "positive" (high risk). Concordance of randomly repeated referral screening tools (156 of 2464) was 96% (kappa = 0.75). In comparison with the pedigree analyses, the referral screening tool demonstrated an overall (high risk by any model) sensitivity of 81.2%, specificity of 91.9%, and discriminatory accuracy of 0.87. CONCLUSIONS: Within the population studied, the referral screening tool seems to be a reliable and valid tool to identify individuals who should be referred for consideration of BRCA1/2 testing. Further examination of the referral screening tool in primary care settings is warranted to assess its impact on the efficiency with which health care providers triage patients to cancer genetics services.