Breast Cancer Genetic Counseling Research Articles

The implementation and outcome of a breast cancer genetic counselling service at Potchefstroom Hospital: a model for outreach

Aim Breast cancer is the most prevalent cancer in South African females, making up 27.1% of all histologically diagnosed cancers in 2020. Although genetic technology and awareness of genetic counselling have improved, genetic counselling services in South Africa remain largely inaccessible. Clinical genetic services are only formally available in four South African provinces and few outreach programmes exist for small towns and cities. Until 2019, genetic counselling services were unavailable in the North West province; however, since then, genetic counsellors from the National Health Laboratory Service and the University of the Witwatersrand have provided genetic counselling services to patients at the Breast Clinic at Potchefstroom Hospital regularly each year. Method The aim of this pilot study was to perform a retrospective file review and report on the implementation and outcomes of the genetic counselling service at the Breast Clinic at Potchefstroom Hospital, from its inception in 2019, until November 2022. Fifty-two patients attended a genetic counselling consultation during that period. Results The majority of patients (83.7%) were diagnosed with an invasive ductal carcinoma, and 57.7% of the patients had a family history of cancer. A total of 62.8% of patients had a histologic grade 3 tumour. A total of 25.5% (12/47) of patients tested positive for a pathogenic variant in BRCA1 or BRCA2. A total of 45 at-risk first-degree relatives were identified who could benefit from predictive testing. Conclusions This study highlights the benefit of offering clinical genetics services through outreach clinics. Being able to offer this service is not only beneficial for the management of the affected individuals, but also for their at-risk relatives. The initiative serves as a positive example of how limited resources can be extended to benefit patients.

Abstract PO3-08-06: Challenges in Implementing Genetic Counseling and Genetic Testing for Breast Cancer: Insights from the First 1000 Families Assessed in a Public University Hospital in Argentina

Abstract Introduction: Integrating genetic testing into breast cancer patients care is crucial for personalized treatment recommendations, risk reduction strategies, and family members evaluation. However, Argentina faces several concerns in implementing these services. Objective: This study aims to explore the challenges encountered in implementing genetic testing for breast cancer, drawing insights from the assessment of the first 1000 patients at a public university hospital in Argentina. Methods: We conducted a retrospective analysis of patients who underwent genetic counseling in our institution from January 2015 to June 2023. We also analyzed patients who underwent surgery from June 2022 to May 2023. Results: 1032 patients were evaluated in our unit. 836 patients (81%) met the National Comprehensive Cancer Network (NCCN) criteria for genetic testing. Genetic testing was requested for 575 patients (68.7%) Only 44% of patients were able to access the test, with 60% receiving only the BRCA1/2 test (see Table 1 and 2 for details). In the analysis of breast cancer surgeries (n=246), 62% (n=154) met the NCCN criteria for genetic testing. However, only 56% of these patients underwent genetic counseling prior to their surgery and only 15 (9.86%) received their results before primary treatment. Discussion Unfortunately, only 9.8% of patients have the results of genetic testing prior to their primary treatment, indicating a critical need for timely referrals and mainstream genetic testing. To counteract, our university hospital's breast cancer unit has taken proactive measures since January 2015. Genetic counseling has been established as a standard of care for all patients, and a streamlined workflow has been implemented to optimize referrals. Trained professionals, including a genetic counselor, psycho-oncologist, and geneticist, have been integrated into core teams. Additionally, healthcare professional continued education has played a pivotal role in improving referrals. Additionally, we have introduced an easy workflow to optimize referrals to genetic counseling. Completion rate of requested genetic tests is concerning, with 56% of tests not being completed, and 60% of the completed tests limited to BRCA1/2. Improving access to genetic testing is imperative. Currently, comprehensive genetic testing is inaccessible to patients without medical coverage, and even those with coverage face difficulties in testing access. Moreover, patient education plays a vital role in promoting the importance of genetic testing and its impact on patient care and their families. In collaboration with the Argentinean Breast Pathology Society, we have developed two informative videos that reinforce knowledge provided by primary care physicians and breast surgeons. Conclusion, Our study is the first in Argentina to analyze the numerous challenges faced in conducting genetic testing for breast cancer in a public hospital. By addressing these challenges collectively, we can facilitate the effective integration of genetic counseling and testing into routine practice for breast cancer patients in Argentina. Table 1: Breast Cancer Genetic Counseling Unit Patients (2015-2023) Table 2: Breast Cancer Genetic Counseling Unit Patients studies (2015-2023) Citation Format: Dolores Mansilla, Diana Bequelman, Jorgelina Cavallero, Hernan Ursino, Berman Gaston, Ipiña Martin, Eduardo Armanasco, Andrea Aguilar, Valeria Caceres, Eugenia Azar. Challenges in Implementing Genetic Counseling and Genetic Testing for Breast Cancer: Insights from the First 1000 Families Assessed in a Public University Hospital in Argentina [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-08-06.

Provider discussion of genetic counseling among high-risk Spanish-preferring Latina breast cancer survivors.

Among high-risk breast cancer (BC) survivors, genetic counseling (GC) and genetic testing (GT) may inform cascade testing and risk management. Compared to non-Hispanic White BC survivors, Spanish-preferring Latina BC survivors are less likely to report discussing GC with a healthcare provider. However, few studies have examined Latinas' experiences with GC/GT, particularly outside of the mainland USA. This study aimed to compare frequency of provider discussion of GC between Spanish-preferring Latina BC survivors living in Florida (FL) and Puerto Rico (PR). We conducted secondary data analysis of baseline assessments from a randomized pilot of an educational intervention for Spanish-preferring Latina BC survivors. Participants (N = 52) were GC/GT-naive, but met clinical criteria for GC/GT referral. Participants self-reported sociodemographic, clinical, and cultural variables, including previous provider discussion of GC. Descriptive statistics characterized frequency of GC discussion. Logistic regression examined the relationships between sociodemographic, clinical, and cultural characteristics and GC discussion. Only 31% of participants reported previous GC discussion. More participants from PR reported having GC discussions (43% vs. 21% in the mainland USA). In multivariable analyses, greater likelihood of GC discussion was associated with PR (vs. mainland USA) residence (odds ratio [OR] = 6.00, p = .03), older age at baseline (OR = 1.19, p = .04), and younger age at BC diagnosis (OR = 0.80, p = .03). Few high-risk Spanish-preferring Latina BC survivors in the mainland USA and PR had discussed GC with their providers. These results highlight a gap in the implementation of evidence-based genetics guidelines. Provider-directed interventions may be needed to increase uptake of GC/GT among Latina BC survivors.

Black Women Are Less Likely to Be Classified as High-Risk for Breast Cancer Using the Tyrer-Cuzick 8 Model

Breast cancer risk assessment is a powerful tool that guides recommendations for supplemental breast cancer screening and genetic counseling. The Tyrer-Cuzick 8 (TC8) model is widely used for calculating breast cancer risk and thus helps determine if women qualify for supplemental screening or genetic counseling. However, the TC8 model may underestimate breast cancer risk in Black women. This study sought to assess this disparity. Data on race, breast density, body mass index (BMI), and TC8 scores were retrospectively extracted from the electronic medical record (EMR). Logistic regressions were run to evaluate racial differences in TC8 scores. Summary and correlation statistics determined relationships between BMI, breast density, and race. Rank biserial correlations were employed to explore the impact of breast density and BMI on TC8 scores. Of 15,356 patients, 5796 were White and 5813 were Black. Black patients had higher rates of BMI ≥ 27 compared with White women (79.2% vs. 45.7%), lower rates of breast density (35.1% vs. 56.2%), and lower rates of high-risk TC8 scores (10.7% vs. 17.5%, OR = 1.6646). There was an inverse relationship between TC8 score and BMI (rrb = - 0.04) and a direct relationship between TC8 score and breast density (rrb = 0.37). Black women are less likely to have high-risk TC8 scores despite having only marginally lower breast cancer incidence rates and higher breast cancer mortality rates than White women. This suggests that the TC8 model underestimates breast cancer risk in Black women, possibly due to lower rates of breast density and higher BMIs among Black women.

Breast Cancer Risk in Women from Ghana Carrying Rare Germline Pathogenic Mutations.

Risk estimates for women carrying germline mutations in breast cancer susceptibility genes are mainly based on studies of European ancestry women. We investigated associations between pathogenic variants (PV) in 34 genes with breast cancer risk in 871 cases [307 estrogen receptor (ER)-positive, 321 ER-negative, and 243 ER-unknown] and 1,563 controls in the Ghana Breast Health Study (GBHS), and estimated lifetime risk for carriers. We compared results with those for European, Asian, and African American ancestry women. The frequency of PV in GBHS for nine breast cancer genes was 8.38% in cases and 1.22% in controls. Relative risk estimates for overall breast cancer were: (OR, 13.70; 95% confidence interval (CI), 4.03-46.51) for BRCA1, (OR, 7.02; 95% CI, 3.17-15.54) for BRCA2, (OR, 17.25; 95% CI, 2.15-138.13) for PALB2, 5 cases and no controls carried TP53 PVs, and 2.10, (0.72-6.14) for moderate-risk genes combined (ATM, BARD1, CHEK2, RAD51C, RAD52D). These estimates were similar to those previously reported in other populations and were modified by ER status. No other genes evaluated had mutations associated at P < 0.05 with overall risk. The estimated lifetime risks for mutation carriers in BRCA1, BRCA2, and PALB2 and moderate-risk genes were 18.4%, 9.8%, 22.4%, and 3.1%, respectively, markedly lower than in Western populations with higher baseline risks. We confirmed associations between PV and breast cancer risk in Ghanaian women and provide absolute risk estimates that could inform counseling in Ghana and other West African countries. These findings have direct relevance for breast cancer genetic counseling for women in West Africa.

Attitudes and training needs of oncologists and surgeons in mainstreaming breast cancer genetic counseling in a low-to-middle income Asian country.

With the advent of poly-ADP-ribose polymerase inhibitor (PARPi) therapies, the focus of genetic testing for breast, ovarian, and other cancers has shifted from risk management to treatment decision-making in high-resource settings. Due to the shortage of genetic counselors worldwide, alternative ways of delivering genetic counseling have been explored, including training nongenetics healthcare professionals (NGHPs) to provide genetic counseling. However, little is known about the feasibility of adopting such models in healthcare settings with insufficient specialists, where population health literacy is low and where access to new therapies may be limited. In this study, we evaluated the attitudes, considerations, and self-efficacy of oncologists, breast surgeons, and general surgeons in mainstreaming breast cancer genetic counseling in Malaysia, a middle-income Asian country with a universal healthcare system. We developed a 32-item survey via a modified Delphi method, which was then distributed via a purposive and network sampling approach. While 77% of respondents expressed interest in providing breast cancer genetic counseling, 85% preferred to refer patients directly to genetic services for genetic counseling and testing. The main considerations for mainstreaming were the cost of genetic testing and PARPi therapy, as well as the availability of support from genetics professionals. Respondents reported a lack of confidence in communicating genetic risk, particularly to patients with poor health literacy, and in the clinical management of patients with variants of uncertain significance. Our results highlight the urgent need to train more NGHPs in providing genetic counseling and testing in low-to-middle income countries, and suggest that the mainstay for genetic counseling in this setting may be for risk management rather than access to PARPi therapy.

Uncertainty Handling in Genetic Risk Assessment and Counseling

In this paper, we consider genetic risk assessment and genetic counseling for breast cancer from the point of view of reliable uncertainty handling. In medical practice, there exist fairly accurate numerical tools predicting breast cancer (or gene mutation) probability based on such factors as the family history of a patient. However, they are too complex to be applied in normal doctors’ offices, so that several simplified, questionnaire-type support tools appeared. This process is highly affected by uncertainty. At the same time, reliability of test interpretations and counseling conclusions is especially important since they have direct influence on humans and their decisions. We show how expert opinions on mutation probabilities can be combined using the Dempster-Shafer theory. Based on multi-criteria binary decision trees and interval analysis, we combine the referral screening tool designed to determine patients at risk of breast cancer (and recommend genetic counseling or testing for them) with three further risk assessment tools available for this purpose. A patient’s confidence in the outcome of a genetic counseling session can be heightened by the proposed method since it combines different sources to provide score ranges leading to more information. Finally, based on this approach, a decision tree for assigning a risk category is proposed which enhances the existing methodology. The great impact of epistemic uncertainty is reflected through large overlapping intervals for the risk classes.

Communication about breast cancer genetic counseling with patients with limited health literacy or a migrant background: evaluation of a training program for healthcare professionals

Access to breast cancer genetic counseling is suboptimal for patients with limited health literacy or a migrant background due to ineffective communication and lack of healthcare professionals’ recommendation. This study examines the effect of a blended training program (Erfo4all) for healthcare professionals on their awareness, knowledge, and self-efficacy towards communication about genetic counseling with patients with limited health literacy or a migrant background. In total, 59 breast surgeons and specialized nurses from 16 Dutch hospitals completed an online module and group training. Knowledge, self-assessed awareness, and self-efficacy were assessed before the training and 33 participants also completed a posttest questionnaire 6 months after the training program. We also assessed the perceived applicability and relevance of the training program from healthcare professionals’ perspectives. We found a significant increase in self-assessed awareness of the prevalence and impact of limited health literacy and in healthcare professionals’ self-efficacy to recognize limited health literacy and to communicate effectively with patients with limited health literacy or a migrant background. We did not find an increase in knowledge score. Almost all healthcare professionals reported that they use the techniques learned in the training, such as the teach-back method and plain language, and felt more confident discussing breast cancer genetic counseling. Our results suggest that a blended training program for healthcare professionals has potential to improve their ability to communicate effectively about breast cancer genetic counseling with patients with limited health literacy or a migrant background and offers a promising way to increase the referral rate for these groups of patients.

Development of a plain-language guide for discussing breast cancer genetic counseling and testing with patients with limited health literacy

PurposeDue to limited health literacy and resulting ineffective communication between healthcare professionals and patients, not all eligible patients are offered breast cancer genetic counseling and testing. We aimed to develop a plain-language guide to increase effective communication about genetic counseling and testing with breast cancer patients with limited health literacy.MethodsTogether with oncological healthcare professionals, we drafted a list of jargon words frequently used during (breast) cancer genetic counseling. In a focus group interview with breast cancer counselees with limited health literacy, who had received genetic counseling before, we reformulated these words in plain language. Low-literate individuals, who are not familiar with breast cancer care or genetic counseling, reflected on the draft of the guide. Completeness, acceptability, and perceived usability were tested in an online questionnaire among healthcare professionals.ResultsThe result is a plain-language guide for genetic counseling and testing with 33 frequently used jargon words and a reformulation of these words in plain language. Acceptability and perceived usefulness of the guide among healthcare professionals (n = 58) were high.ConclusionThe plain-language guide provides opportunities to facilitate communication about genetic counseling and testing with patients with limited health literacy and could enhance opportunities for patients to make informed decisions to participate in genetic testing. As the intention from healthcare professionals to use the plain-language guide is high, implementation of the guide in a real-life setting seems promising.

Functional analysis of patient-derived PALB2 missense variants of uncertain significance.

1531 Background: Inherited PALB2 pathogenic variants are associated with an increased lifetime risk for breast cancer development. However, the interpretation of numerous PALB2 missense variants of uncertain significance (VUS) identified in germline genetic testing remains a challenge. Here, we assessed the impact of breast cancer patient-derived VUS on PALB2 function and identified pathogenic PALB2 missense variants that may increase cancer risk. Methods: A total of seven potentially pathogenic PALB2 VUS identified in 2,279 breast cancer patients were selected for functional analysis. All these selected VUS were assessed by SIFT, Align-GVGD, and PolyPhen2 in silico and were predicted to be deleterious by at least two in silico algorithms. The p.L35P [c.104T > C] variant was also included, for which pathogenicity has been recently confirmed. The effects of the VUS on the homologous recombination (HR) activity of PALB2 were tested by U2OS/DR-GFP reporting system. Functional characterization was further validated by protein co-immunoprecipitation and RAD51 recruitment assay. Results: PALB2 variants p.L24F [c.72G > C] and p.L35P [c.104T > C] showed the most significant disruption to the HR activity of PALB2 relative to the wild-type condition, retaining only 52.2% ( p = 0.0013) and 8.5% ( p < 0.0001) of HR activity respectively. Moderate but statistically significant HR deficiency was observed for four other variants (p.P405A [c.1213C > G], p.T1012I [c.3035C > T], p.E1018D [c.3054G > C], and p.T1099M [c.3296C > T]). We found no statistical differences for the p.K628N [c.1884G > T] and p.R663C [c.1987C > T] in the HR activity compared to wild-type PALB2. The p.L24F and p.L35P variants compromised the BRCA1-PALB2 interaction and reduced RAD51 foci formation in response to DNA damage. Conclusions: We have identified a novel patient-derived pathogenic PALB2 missense variant, p.L24F [c.72G > C], that compromises PALB2-mediated HR activity. We suggest the integration of the identified pathogenic variants into breast cancer genetic counseling and individualized treatment regimens for better clinical outcomes.

Promoting genetic counseling among African American women with hereditary risk for breast cancer.

e13639 Background: Breast cancer (BC) mortality is substantially higher for African American (AA) women compared to their white counterparts. Genetic counseling (GC) is a key step in management of women with hereditary BC risk, but medically underserved women of color are less likely to receive these services. We report preliminary data from a pilot study examining the impact of a culturally sensitive, multimedia educational video created to motivate AA women with hereditary BC risk to attend GC. Development of the intervention was guided by the Integrative Model of Behavioral Prediction and qualitative research with the target audience. Methods: AA women eligible for GC for hereditary BC according to national criteria were identified through cancer genetic risk assessment (CGRA) performed at the time of a screening mammogram at the University of Illinois Health System in Chicago, IL, and were invited to participate in the study. Participants completed a baseline survey, viewed the educational intervention, and completed a post-intervention survey. The surveys included five-item Likert scales on intentions to act on the information presented, normative beliefs about GC, knowledge, and acceptability of the intervention. Responses were summarized as frequencies and proportions, and changes pre/post-intervention were evaluated using McNemar’s test. Results: The proportion of participants (n = 30) who rated they were “Extremely Likely” to make an appointment with a genetic counselor increased from 50% at baseline to 70% following the intervention (p = 0.04). After viewing the video, the proportion who rated they were “Extremely Likely” to speak with their doctor about genetic counseling increased from 60% to 77% (p = 0.10). There was a 16.6% increase (p = 0.05) in the proportion of women who indicated their family would be interested in learning more about GC, and 96.6% and 90% of participants agreed that the intervention video was enjoyable to watch and that they could relate to what the actors were saying, respectively. Changes in intentions to act on the information presented were not accompanied by changes in knowledge. Conclusions: A culturally sensitive multimedia intervention based on a theoretical model of health behavior increased intentions to attend GC among high risk AA women. The intervention was enjoyable for minority women to watch and increased intentions to discuss GC with family members. These findings indicate that culturally tailored motivational interventions have the potential to increase uptake of GC in underserved communities.

Systematic development of a training program for healthcare professionals to improve communication about breast cancer genetic counseling with low health literate patients

There is a disproportionate underuse of genetic testing in breast cancer patients from lower education or migrant background. Within these groups, communication about referral to genetic counseling appears challenging due to limited health literacy and cultural barriers. Our aim was to develop and evaluate a training program for healthcare professionals (breast surgeons and specialized nurses), to increase effective communication. We systematically developed a blended training program based on patients’ and healthcare professionals’ needs and preferences. Prior to the training, we assessed awareness, knowledge and self-efficacy of healthcare professionals. Acceptability and usefulness of the training program were assessed directly after the training. Healthcare professionals (n = 65) from 17 hospitals showed moderate to high awareness and knowledge about the prevalence and impact of limited health literacy. They were aware of cultural factors that influence communication. However, they did not feel confident in recognizing limited health literacy and their self-efficacy to communicate effectively with these patients was low. The training program was rated as acceptable and useful. Healthcare professionals lack confidence to effectively communicate with patients with limited health literacy or migrant background. The training program offers opportunities to improve communication about referral to breast cancer genetic counseling.

Molecular Mechanisms of PALB2 Function and Its Role in Breast Cancer Management.

Partner and localizer of BRCA2 (PALB2) is vital for homologous recombination (HR) repair in response to DNA double-strand breaks (DSBs). PALB2 functions as a tumor suppressor and participates in the maintenance of genome integrity. In this review, we summarize the current knowledge of the biological roles of the multifaceted PALB2 protein and of its regulation. Moreover, we describe the link between PALB2 pathogenic variants (PVs) and breast cancer predisposition, aggressive clinicopathological features, and adverse clinical prognosis. We also refer to both the opportunities and challenges that the identification of PALB2 PVs provides in breast cancer genetic counseling and precision medicine.

Abstract P6-08-37: A new workflow for breast cancer genetic counseling referral. Experience of an public oncological reference center in Argentina

Abstract Background: Argentina is a country with inequalities in terms of healthcare, specially in genetics diseases. The lack of knowledge about hereditary cancer, the small number of genetic counselors and the difficulty of access to genetic testing are barriers to overcome to position genetic counseling (GC) as a standard of care. Objective: Describe our experience implementing GC as a standard of care for all patients with breast cancer (BC), and propose a new workflow to optimize referral to GC. The aim is to obtain GC and genetic testing prior to the primary treatment. Methods: In January 2015, the breast cancer unit established GC as a standard of care on all their patients. The institution didn’t have GC, so a breast cancer surgeon, part of the core team, was trained in GC and the rest of the team was trained to refer patients according to international guidelines. That surgeon and a psycho-oncologist formed the breast cancer genetic counseling section (BCGCS). They have interviewed patients and their families and have supported them and their medical team all over the GC process and testing. Results: From January 2015 to December 2018, 535 patients were evaluated by the BCGCS. 63% of patients were refered by breast surgeons, 12% by clinical oncologist, 19% by other units, 1% by the patients themselves and 5% from other institutions. The average time until the first GC consultation was 35 days (1-60 days). A minimum of two GC consultations per patient were performed. 243 patients were referred for genetic testing and 280 were not (27 without criteria, 35 were not index case, 19 psychological reasons and 147 patients were requested additional information). From the 243 patients, 139 didn’t have access to genetic testing due to lack of health insurance coverage. 104 test were successfully performed: 2 exomes (2 VUS: CHEK2 and TSC2), 81 BRCA1/2 (20 positives), 8 panels (3 VUS: ATM, RECQL, STK11) and 13 family mutations (5 positives: 4 BRCA and 1 CHEK2). Only two patients had a positive BRCA test before their primary treatment, both chose a bilateral mastectomy and one of them was included in the Olympia trial. Due to the success of the BCGCS, in 2017 a gynecologist and in 2018 an oncologist were trained in GC. The first one is part of the gynecological cancer unit and the second is part of the gastrointestinal cancer unit. Conclusion: Due to the presence of trained professionals as part of core teams, those units were continuously educated in genetics. That led to more and earlier referral to GC. We propose the following workflow to achieve better and more referrals of patients to GC, optimizing time and resources. Proposed WorkflowBackground requirements: Surgeon specialized in breast cancer trained in GC and Psycho-oncologist with basic knowledge of cancer genetics. Breast unit trained in hereditary cancer and referral guidelines.-Step one) Admission to breast unit with identification of patients with genetic counseling criteria according with national and international guidelines. *-Step two) Treatment Focus Genetic Testing is needed? (metastatic breast cancer, triple negative breast cancer, breast and ovarian cancer)1) Yes (always request psycho-logical support and explain the workflow)1A) Had family history of cancer?(1Aa) Yes: request a limited panel (BRCA1 / 2, PALB2, Tp53, Pten and other gene if an other syndrome is suspected) and send it to BCGCS**(1Ab) No: request BRCA1 / 2 and PALB2 testing(1Abi) Negative result. End of process(1Abii) Positive result or VUS: send to BCGCS**2) No: send to BCGCS.*** Rapid genetic testing is strongly encouraged.** Always explain about genetic counseling process and information needed prior to consultation. Citation Format: Maria Dolores Mansilla Figueroa, D Bequelman, J Cavallero, O Sturla, H Ursino, V Caceres, E Gonzalez. A new workflow for breast cancer genetic counseling referral. Experience of an public oncological reference center in Argentina [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 P6-08-37.

Genetic counseling, genetic testing, and risk perceptions for breast and colorectal cancer: Results from the 2015 National Health Interview Survey

We examined what proportion of the U.S. population with no personal cancer history reported receiving either genetic counseling or genetic testing for cancer risk, and also the association of these behaviors with cancer risk perceptions.We used data from the 2015 National Health Interview Survey. Objective relative risk scores for breast (women) and colorectal (men and women) cancer risk were generated for individuals without a personal history of cancer. Participants' risk perceptions were compared with their objective relative risk.Of 12,631 women, 1.2% reported receiving genetic counseling and 0.8% genetic testing for hereditary breast cancer risk. Of 15,085 men and women, 0.8% reported receiving genetic counseling and 0.3% genetic testing for hereditary colorectal cancer risk. Higher breast cancer risk perception was associated with genetic counseling (OR: 4.31, 95%CI: 2.56, 7.26) and testing (OR: 3.56, 95%CI: 1.80, 7.03). Similarly, higher perception of colorectal cancer risk was associated with genetic counseling (OR: 5.04, 95%CI: 2.57, 9.89) and testing (OR: 5.92, 95%CI: 2.40, 14.63). A higher proportion of individuals with colorectal cancer risk perceptions concordant with their objective risk (vs. discordant) had undergone genetic counseling or testing for colorectal cancer risk. Concordant risk perceptions for breast cancer were not associated with breast cancer genetic counseling or testing.Given frequent dialogue about implementing population level programs involving genetic services for cancer risk, policy makers and investigators should consider the role of risk perceptions in the effectiveness and design of such programs and potential strategies for addressing inaccuracies in risk perceptions.

Economic modeling of risk-adapted screen-and-treat strategies in women at high risk for breast or ovarian cancer.

The 'German Consortium for Hereditary Breast and Ovarian Cancer' (GC-HBOC) offers women with a family history of breast and ovarian cancer genetic counseling. The aim of this modeling study was to evaluate the cost-effectiveness of genetic testing for BRCA 1/2 in women with a high familial risk followed by different preventive interventions (intensified surveillance, risk-reducing bilateral mastectomy, risk-reducing bilateral salpingo-oophorectomy, or both mastectomy and salpingo-oophorectomy) compared to no genetic test. A Markov model with a lifelong time horizon was developed for a cohort of 35-year-old women with a BRCA 1/2 mutation probability of ≥ 10%. The perspective of the German statutory health insurance (SHI) was adopted. The model included the health states 'well' (women with increased risk), 'breast cancer without metastases', 'breast cancer with metastases', 'ovarian cancer', 'death', and two post (non-metastatic) breast or ovarian cancer states. Outcomes were costs, quality of life years gained (QALYs) and life years gained (LYG). Important data used for the model were obtained from 4380 women enrolled in the GC-HBOC. Compared with the no test strategy, genetic testing with subsequent surgical and non-surgical treatment options provided to women with deleterious BRCA 1 or 2 mutations resulted in additional costs of €7256 and additional QALYs of 0,43 (incremental cost-effectiveness ratio of €17,027 per QALY; cost per LYG: €22,318). The results were robust in deterministic and probabilistic sensitivity analyses. The provision of genetic testing to high-risk women with a BRCA1 and two mutation probability of ≥ 10% based on the individual family cancer history appears to be a cost-effective option for the SHI.

Electronically ascertained extended pedigrees in breast cancer genetic counseling.

A comprehensive pedigree, usually provided by the counselee and verified by medical records, is essential for risk assessment in cancer genetic counseling. Collecting the relevant information is time-consuming and sometimes impossible. We studied the use of electronically ascertained pedigrees (EGP). The study group comprised women (n = 1352) receiving HBOC genetic counseling between December 2006 and December 2016at Landspitali in Iceland. EGP's were ascertained using information from the population-based Genealogy Database and Icelandic Cancer Registry. The likelihood of being positive for the Icelandic founder BRCA2 pathogenic variant NM_000059.3:c.767_771delCAAAT was calculated using the risk assessment program Boadicea. We used this unique data to estimate the optimal size of pedigrees, e.g., those that best balance the accuracy of risk assessment using Boadicea and cost of ascertainment. Sub-groups of randomly selected 104 positive and 105 negative women for the founder BRCA2 PV were formed and Receiver Operating Characteristics curves compared for efficiency of PV prediction with a Boadicea score. The optimal pedigree size included 3° relatives or up to five generations with an average no. of 53.8 individuals (range 9-220) (AUC 0.801). Adding 4° relatives did not improve the outcome. Pedigrees including 3° relatives are difficult and sometimes impossible to generate with conventional methods. Pedigrees ascertained with data from pre-existing genealogy databases and cancer registries can save effort and contain more information than traditional pedigrees. Genetic services should consider generating EGP's which requires access to an accurate genealogy database and cancer registry. Local data protection laws and regulations have to be addressed.

The Cancer Worry Scale Revised for Breast Cancer Genetic Counseling.

The Cancer Worry Scale was revised to be used in breast cancer genetic counseling (CWS-GC). This scale is used to identify dimensions that are relevant in the genetic counseling context, such as worry about developing breast cancer, impact of worries on daily life, and risk perception in women attending a counseling session for BRCA1/2 mutations. The aim of this study was to estimate the psychometric properties of the CWS-GC in a sample of Italian women. A total of 304 women aged 19 to 90 years, 58% with history and 42% with no history of breast or ovarian cancer, participated in the study. Validity, reliability, and sensitivity to change of the CWS-GC were assessed. Confirmatory factor analysis suggested a 2-factor structure of the CWS-GC measuring cancer worry and risk perception and with Cronbach's α coefficients of .90 and .70, respectively. Criterion validity was attested by substantial yet not overlapping correlations with anxiety and fear of medical procedures. In a subsample of 50 women, test-retest reliability at a 4-week interval ranged from 0.70 to 0.87, and the CWS-GC was able to detect small to medium changes 1 month after genetic counseling. Overall, the CWS-GC showed good psychometric characteristics in this population. The CWS-GC would be appropriate for use by healthcare professionals to better understand how women react and adapt to information on genetic cancer risk to provide them with emotional support and encourage surveillance behaviors.

Breast cancer genetic counseling among Dutch patients from Turkish and Moroccan descent: participation determinants and perspectives of patients and healthcare professionals

Lower participation rates in cancer genetic counseling are observed among different ethnic minorities. The goal of our study is to gain insight into determinants of Turkish and Moroccan patients’ participation in breast cancer genetic counseling and DNA testing, from the point of view of healthcare professionals and patients. Questionnaire-based telephone interviews about awareness, perceptions, and reasons for (non-) participation in cancer genetic counseling were conducted with 78 Dutch breast cancer patients from Turkish and Moroccan descent. The interviews were held in Arabic, Berber, Turkish, or Dutch by bilingual research assistants. Additionally, 14 breast cancer patients participated in one of two focus group meetings, and two focus groups were held with 11 healthcare professionals. SPSS and QSR Nvivo were used to examine the quantitative and qualitative data, respectively. Half of the total group of patients (N = 78) and 79% of patients eligible for genetic counseling and testing (N = 33) were aware of the possibility of genetic counseling. The most important determinants for nonparticipation in genetic counseling were experienced difficulties in patient-doctor communication, cultural factors (e.g., social norms), limited health literacy, limited knowledge of the family cancer history, and anxiety about cancer. Religious beliefs and knowing personal and family members’ breast cancer risks were motives to obtain genetic counseling. Despite the fact that our study showed that Moroccan and Turkish women reported several personal motives to obtain genetic counseling and testing (GCT), patients and healthcare professionals experience significant language and health literacy difficulties, which make it harder to fully access health care such as genetic counseling and testing.

Molecular characterization, homology modeling and docking studies of the R2787H missense variation in BRCA2 gene: Association with breast cancer

The significance of many BRCA unclassified variants (UVs) has not been evaluated. Classification of these variations as neutral or pathogenic presents a significant challenge and has important implications for breast and ovarian cancer genetic counseling. Here we report a combined molecular and computational approach to classify BRCA UVs missense variations. By using the LOH (Loss of heterozygosity) analysis at the BRCA1/BRCA2 loci, five bioinformatics approaches namely fathmm, PhD-SNP, SNAP, MutationTaster and Human Splicing Finder and the association with the clinico-pathological characteristics related to BRCA tumors, we were able to classify the R2787H (in BRCA2 gene) variant as pathogenic. Then, to investigate the functional role of the R2787H variation in altering BRCA2 structure, the homology model of this variant was constructed using the Rattus norvegicus BRCA2 (PDB ID: 1IYJ) as a template. The predicted model was then assessed for stereochemical quality and side chain environment. Furthermore, docking and binding free energy simulations were performed to investigate the ssDNA-BRCA2 complex interaction. Binding energy value calculation proves that this substitution affects the complex stability. Moreover, this alteration was not found in one hundred healthy controls. These findings suggest that R2787H variant could have potential functional impact. Our approach might be useful for evaluation of BRCA unclassified variants. However additional functional analyzes may provide appropriate assessment to classify such variants.