Factors that differentiate cancer risk management decisions among females with pathogenic/likely pathogenic variants in PALB2, CHEK2, and ATM.

PURPOSE: Following disclosure of pathogenic or likely pathogenic variants in hereditary cancer genes, patients face cancer risk management decisions. Through this mixed-methods study, we investigated cancer risk management decisions among females with pathogenic or likely pathogenic variants in PALB2, CHEK2, and ATM to understand why some patients follow National Comprehensive Cancer Network guidelines, whereas others do not. METHODS: Survey and interview data were cross-analyzed using a 3-stage approach. Identified factors were used to conduct coincidence analysis and differentiate between combinations of factors that result in following or not following guidelines. RESULTS: Of the 13 participants who underwent guideline inconsistent prophylactic surgery, 12 fit 1 of 3 unique patterns: (1) cancer-related anxiety in the absence of trust in care, (2) provider recommending surgery inconsistent with National Comprehensive Cancer Network guidelines, or (3) surgery occurring before genetic testing. Two unique patterns were found among 18 of 20 participants who followed guidelines: (1) anxiety along with trust in care or (2) lack of anxiety and no prophylactic surgery before testing. CONCLUSION: Health care provider recommendations and trust in care may influence whether individuals receive care that is congruent with risk levels conferred by specific genes. Interventions are needed to improve provider knowledge, patient trust in non-surgical care, and patient anxiety.

An overview of genetic services delivery for hereditary breast cancer.

Breast cancer is the most common cancer diagnosed in women worldwide, with approximately 5-10% of cases attributed to high penetrance hereditary breast cancer (HBC) genes. The tremendous advances in precision oncology have broadened indications for germline genetic testing to guide both systemic and surgical treatment, with increasing demand for cancer genetic services. The HBC continuum of care includes (1) identification, access, and uptake of genetic counseling and testing; (2) the delivery of genetic counseling and testing services; and (3) initiation of guideline-adherent follow-up care and family communication of results. Challenges to delivering care on the HBC care continuum include factors such as access to services, cost, discrimination and bias, and lack of education and awareness, which can be mitigated through implementing a multi-level approach. This includes strategies such as increasing awareness and utilization of genetic counseling and testing, developing new methods to meet the growing demand for genetic services, and improving the uptake of follow-up care by increasing patient and provider awareness of the management recommendations.

Qualitative Methods for Refining a Web-Based Educational Tool for Patients Focused on Inherited Cancer Predisposition.

To address the increasing demand for inherited cancer genetic testing, we developed and evaluated a web-based educational tool to streamline genetic counseling (GC). Consented patients viewed the initial prototype containing core content (Version 1-Core) and provided feedback through three open-ended survey questions. Additional data were collected through individual interviews from a subgroup who viewed an enhanced version (Version 1-Enhanced), consisting of the same core content and additional optional content. Data were coded to synthesize most commonly repeated themes and conceptualize action items to guide refinement strategies. Of 305 participants, 80 responded to open-ended survey questions to suggest refinement strategies, after viewing Version 1-Core. Interviews with a subgroup of seven participants, who viewed Version 1-Enhanced, provided additional feedback. Of 11 unique action items identified, five overlapped across datasets (provide instructions, simplify language, improve visuals, embed knowledge questions with explanations, include more insurance-related information), three were identified only through open-ended survey data (incorporate automatic progression, clarify test result information, increase interactive content), and three were identified only through interviews (ensure core content is viewed, incorporate progress bar, feature embedded optional content at the end of the tool). Ten action items aligned with underlying tool objectives to provide an interactive online pre-test GC solution and were used to guide refinement strategies. Our results demonstrate the value of rigorous qualitative data collection and analysis in health research and the use of the self-directed learning framework and eHealth strategies to leverage technology in scaling up and innovating the delivery of pre-test GC for inherited cancer.

Impact of molecular subtype and race on HR+, HER2- breast cancer survival.

PURPOSE: There is an urgent need to understand the biological factors contributing to the racial survival disparity among women with hormone receptor-positive (HR+), HER2- breast cancer. In this study, we examined the impact of PAM50 subtype on 10-year mortality rate in women with HR+, HER2- breast cancer by race. METHODS: Women with localized, HR+, HER2- breast cancer diagnosed between 2002 and 2012 from two population-based cohorts were evaluated. Archival tumors were obtained and classified by PAM50 into four molecular subtypes (i.e., luminal A, luminal B, HER2-enriched, and basal-like). The molecular subtypes within HR+, HER2- breast cancers and corresponding 10-year mortality rate were compared between Black and Non-Hispanic White (NHW) women using Cox proportional hazard ratios and survival analysis, adjusting for covariates. RESULTS: In this study, 318 women with localized, HR+, HER2- breast cancer were included-227 Black (71%) and 91 NHW (29%). Young Black women (age ≤ 50) had the highest proportion of HR+, non-luminal A tumors (47%), compared to young NHW (10%), older Black women (31%), and older NHW (30%). Overall, women with HR+, non-luminal A subtypes had a higher 10-year mortality rate compared to HR+, luminal A subtypes after adjustment for age, stage, and income (HR 4.21 for Blacks, 95% CI 1.74-10.18 and HR 3.44 for NHW, 95% CI 1.31-9.03). Among HR+, non-luminal A subtypes there was, however, no significant racial difference in 10-yr mortality observed (Black vs. NHW: HR 1.23, 95% CI 0.58-2.58). CONCLUSION: Molecular subtype classification highlights racial disparities in PAM50 subtype distribution among women with HR+, HER2- breast cancer. Among women with HR+, HER2- breast cancer, racial survival disparities are ameliorated after adjusting for molecular subtype.

IMProving care After inherited Cancer Testing (IMPACT) study: protocol of a randomized trial evaluating the efficacy of two interventions designed to improve cancer risk management and family communication of genetic test results.

BACKGROUND: Implementing genetic testing for inherited cancer predisposition into routine clinical care offers a tremendous opportunity for cancer prevention and early detection. However, genetic testing itself does not improve outcomes; rather, outcomes depend on implemented follow-up care. The IMPACT study is a hybrid type I randomized effectiveness-implementation trial to simultaneously evaluate the effectiveness of two interventions for individuals with inherited cancer predisposition focused on: 1) increasing family communication (FC) of genetic test results; and 2) improving engagement with guideline-based cancer risk management (CRM). METHODS: This prospective study will recruit a racially, geographically, and socioeconomically diverse population of individuals with a documented pathogenic/likely pathogenic (P/LP) variant in an inherited cancer gene. Eligible participants will be asked to complete an initial trial survey and randomly assigned to one of three arms: A) GeneSHARE, a website designed to increase FC of genetic test results; B) My Gene Counsel's Living Lab Report, a digital tool designed to improve understanding of genetic test results and next steps, including CRM guidelines; or C) a control arm in which participants continue receiving standard care. Follow-up surveys will be conducted at 1, 3, and 12 months following randomization. These surveys include single-item measures, scales, and indices related to: 1) FC and CRM behaviors and behavioral factors following the COM-B theoretical framework (i.e., capability, opportunity, and motivation); 2) implementation outcomes (i.e., acceptability, appropriateness, exposure, and reach); and 3) other contextual factors (i.e., sociodemographic and clinical factors, and uncertainty, distress, and positive aspects of genetic test results). The primary outcomes are an increase in FC of genetic test results (Arm A) and improved engagement with guideline-based CRM without overtreatment or undertreatment (Arm B) by the 12-month follow-up survey. DISCUSSION: Our interventions are designed to shift the paradigm by which individuals with P/LP variants in inherited cancer genes are provided with information to enhance FC of genetic test results and engagement with guideline-based CRM. The information gathered through evaluating the effectiveness and implementation of these real-world approaches is needed to modify and scale up adaptive, stepped interventions that have the potential to maximize FC and CRM. TRIAL REGISTRATION: This study is registered at Clinicaltrials.gov (NCT04763915, date registered: February 21, 2021). PROTOCOL VERSION: September 17th, 2021 Amendment Number 04.

Family communication of genetic test results among women with inherited breast cancer genes.

Identification of inherited breast cancer may guide care. These benefits can be amplified through communication of genetic test results with at-risk family members and subsequent family testing (FT). Females with a pathogenic/likely pathogenic (P/LP) variant in BRCA1/2, PALB2, CHEK2, and/or ATM were surveyed about family communication (FC) of genetic test results and FT. Comparisons were made across genes. The 235 participants with P/LP variants (186 BRCA1/2, 28 PALB2, 15 CHEK2, and 6 ATM) had a median age of 54 and most were non-Hispanic whites (89%) with a prior breast cancer diagnosis (61%). When controlling for other variables, FC was higher among younger participants (p<.0001), those with high FC self-efficacy (p=.019), and those with P/LP variants in BRCA1/2 compared to PALB2 (p =.040) and ATM/CHEK2 (p =.032). Higher rates of FC and FT were also observed among female relatives and relatives of closer kinship. Overall 94% of participants would find one or more resources helpful with FC and 70% reported using FC resources when telling family members about their genetic test result. The three most commonly used resources included the following: (a) a family sharing letter (38%); (b) printed materials (30%); and (c) web-based information (23%). Among the 86% who spoke with a genetic counselor (GC), 93% were given at least one FC resource and the three most common resources GCs provided to participants overlapped with the resources participants would find helpful and those that were used. Our results suggest lower FC and FT rates among women with P/LP variants in genes other than BRCA1/2, the reasons for which should be evaluated in future studies. As more data to refine cancer risks and management are generated across these other inherited breast cancer genes, strategies to improve FC and FT are needed to amplify the benefits of genetic testing.

Breast cancer screening implications of risk modeling among female relatives of ATM and CHEK2 carriers.

BACKGROUND: With the increasing use of multigene panel tests, pathogenic and likely pathogenic (P/LP) variants are identified more frequently in the moderate-penetrance breast cancer genes ATM and CHEK2. Lifetime breast cancer risk among women with P/LP variants in these genes generally exceeds 20%, meeting the threshold at which high-risk breast cancer screening through breast magnetic resonance imaging (MRI) is recommended. METHODS: Among a registry-based sample of 56 ATM and 69 CHEK2 carriers, the authors sought to determine the percentage of relatives in whom a P/LP variant would impact breast cancer surveillance. Lifetime breast cancer risks for unaffected, female first-degree and second-degree relatives were estimated using the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA). RESULTS: Among first-degree relatives of ATM and CHEK2 carriers, only 22.6% and 14.9%, respectively, were found to have lifetime breast cancer risks of ≥20% based on family cancer history alone; however, when including the proband's P/LP variant in the model, these percentages increased significantly to 56.6% and 55.3%, respectively (P < .0001 and P < .0001, respectively). Similar increases in lifetime breast cancer risks were found among second-degree relatives. CONCLUSIONS: The results of the current study suggest that the majority of female first-degree and second-degree relatives of ATM and CHEK2 carriers do not qualify for breast MRI based on family cancer history alone. Therefore, testing for these genes, as well as awareness of positive moderate-penetrance breast cancer gene results in the family, may impact MRI eligibility. These findings highlight the potential usefulness of and need for breast cancer risk models that incorporate moderate-penetrance gene positivity to inform screening recommendations among at-risk family members.

Cancer risk management among female BRCA1/2, PALB2, CHEK2, and ATM carriers.

PURPOSE: Identification of inherited breast cancer may guide cancer risk management. We sought to compare risk management practices across women with inherited breast cancer genes. METHODS: Females with a pathogenic/likely pathogenic (P/LP) variant in BRCA1/2, PALB2, CHEK2, and/or ATM were surveyed about cancer risk management. Comparisons were made across genes. RESULTS: The 235 participants with P/LP variants (186 BRCA1/2, 28 PALB2, 15 CHEK2, and 6 ATM) had a median age of 54 and 61% had a prior breast cancer diagnosis. For women with P/LP variants in BRCA1/2, PALB2, and ATM/CHEK2, bilateral mastectomy (BM) rates were 79%, 61%, and 52%, and bilateral oophorectomy (BO) rates were 89%, 30%, and 37%, respectively. Among women with P/LP variants in PALB2 and ATM/CHEK2, 27% of those who had a BO had a family history of ovarian cancer. Contralateral mastectomy rates for women with P/LP variants in PALB2 and ATM/CHEK2 with unilateral breast cancer were 60% and 58%, and BM rates for those without breast cancer were 57% and 29%, respectively. CONCLUSION: These findings suggest high rates of both contralateral mastectomies among those with unilateral breast cancer and BM among those without a breast cancer diagnosis across women with P/LP variants in high and moderate penetrance breast cancer genes. BO was also often utilized for risk reduction across these women. These findings suggest potential overtreatment through risk-reducing surgery, and highlight the importance of promoting guideline-adherent, risk-appropriate care.

Disparities in BRCA counseling across providers in a diverse population of young breast cancer survivors.

PURPOSE: All women diagnosed with breast cancer (BC) ≤age 50 should be referred for genetic counseling (GC) and testing. We sought to compare differences in provider practices and access across a racially and ethnically diverse population of young BC survivors. METHODS: A registry-based sample of women diagnosed with invasive BC ≤age 50 from 2009 to 2012 was recruited through the Florida Cancer Registry, and completed a questionnaire and medical record release. Differences were compared across those tested with or without the involvement of a board-certified or credentialed genetics health professional (GHP) in (1) clinical and demographic variables and (2) pretest GC elements. RESULTS: Of 1622 participants, there were 440 Blacks, 285 Hispanics, and 897 Non-Hispanic Whites. Of 831 participants with medical record verification of testing provider, 170 (20%) had documentation of GHP involvement. Among the 613 who recalled a pretest discussion and had GC elements collected, those with GHP involvement were significantly more likely to recall the seven recognized GC elements. CONCLUSION: GHP involvement was associated with adherence to nationally recommended best practices. With the expanding importance of identifying inherited cancers, it is critical to ensure equitable access to best practices across all populations.

A Web-Based Tool to Automate Portions of Pretest Genetic Counseling for Inherited Cancer.

BACKGROUND: Increasing demand for genetic testing for inherited cancer risk coupled with a shortage of providers trained in genetics highlight the potential for automated tools embedded in the clinic process to meet this demand. We developed and tested a scalable, easy-to-use, 12-minute web-based educational tool that included standard pretest genetic counseling elements related to panel-based testing for multiple genes associated with cancer risk. METHODS: The tool was viewed by new patients at the Vanderbilt Hereditary Cancer Clinic before meeting with a board-certified genetics professional. Pre- and post-tool surveys measured knowledge, feeling informed/empowered to decide about testing, attitudinal values about genetic testing, and health literacy. Of the initial 100 participants, 50 were randomized to only have knowledge measured on the post-tool survey to assess for a priming effect. RESULTS: Of 360 patients approached, 305 consented and completed both the pre- and post-tool surveys, with a mean age of 47 years, including 80% female patients and 48% patients with cancer. Survey results showed an increase in knowledge and feeling informed/empowered after viewing the tool (P<.001), but no significant change in attitude (P=.64). Post-tool survey data indicated no difference in median knowledge between low and high health literacy groups (P=.30). No priming effect was present among the initial 100 participants (P=.675). CONCLUSIONS: Viewing the educational tool resulted in significant gains in knowledge across health literacy levels, and most individuals felt informed and empowered to decide about genetic testing. These findings indicate that the use of an automated pretest genetic counseling tool may help streamline the delivery of genetic services.

Pathological Concentration of C-reactive Protein is Correlated to Increased Concentrations of Quetiapine, But Not of Risperidone, Olanzapine and Aripiprazole in a Naturalistic Setting.

INTRODUCTION: Infections can alter drug clearance, but the impact of inflammation-induced changes is still not well known. The aim of the investigation was to examine the effect of pathological C-reactive protein (CRP) values (≥0.5 mg/dL) and leukocyte count on the metabolism of 4 different atypical antipsychotics. METHODS: Steady-state serum concentrations of individual patients under therapy with risperidone (n=45), aripiprazole (n=30), olanzapine (n=24), and quetiapine (n=166) were retrospectively analyzed during a period of inflammation by Spearman's Rho correlation analysis. Mann-Whitney U test was applied for comparison of patients with serum concentrations above and below the upper limit of the therapeutic reference range of each target drug with regard to CRP concentration and leukocyte count. Linear regression analysis was applied to correct for confounding parameters age and sex. RESULTS: Pathological concentrations of CRP were significantly associated with elevated values of C/D of quetiapine (n=166, Spearman's Rho: r=0.269, p<0.001; linear regression: p<0.001). Among patients with quetiapine serum concentrations below 500 ng/mL, CRP concentrations were significantly (p=0.006) lower compared to patients with quetiapine concentrations above 500 ng/mL. A trend for a positive correlation between CRP and serum concentration was found for olanzapine (n=24, Spearman's Rho: r=0.385, p=0.063; linear regression: p=0.086). CONCLUSION: During a period of inflammation in patients taking quetiapine, according to our results, attention in dosing strategies is required to prevent toxic plasma concentrations.

Racial disparities in BRCA testing and cancer risk management across a population-based sample of young breast cancer survivors.

BACKGROUND: Breast cancer (BC) disparities may widen with genomic advances. The authors compared non-Hispanic white (NHW), black, and Hispanic BC survivors for 1) cancer risk-management practices among BRCA carriers and 2) provider discussion and receipt of genetic testing. METHODS: A population-based sample of NHW, black, and Hispanic women who had been diagnosed with invasive BC at age 50 years or younger from 2009 to 2012 were recruited through the state cancer registry. Multiple logistic regression was used to compare cancer risk-management practices in BRCA carriers and associations of demographic and clinical variables with provider discussion and receipt of testing. RESULTS: Of 1622 participants, 159 of 440 (36.1%) black women, 579 of 897 (64.5%) NHW women, 58 of 117 (49.6%) Spanish-speaking Hispanic women, and 116 of 168 (69%) English-speaking Hispanic women underwent BRCA testing, of whom 90 had a pathogenic BRCA mutation identified. Among BRCA carriers, the rates of risk-reducing mastectomy and risk-reducing salpingo-oophorectomy were significantly lower among black women compared with Hispanic and NHW women after controlling for clinical and demographic variables (P = .025 and P = .008, respectively). Compared with NHW women, discussion of genetic testing with a provider was 16 times less likely among black women (P < .0001) and nearly 2 times less likely among Spanish-speaking Hispanic women (P = .04) after controlling for clinical and sociodemographic factors. CONCLUSIONS: The current results suggest that the rates of risk-reducing salpingo-oophorectomy are lower among black BRCA carriers compared with their Hispanic and NHW counterparts, which is concerning because benefits from genetic testing arise from cancer risk-management practice options. Furthermore, lower BRCA testing rates among blacks may partially be because of a lower likelihood of provider discussion. Future studies are needed to improve cancer risk identification and management practices across all populations to prevent the widening of disparities. Cancer 2017;123:2497-05. © 2017 American Cancer Society.

The Development and Evaluation of Novel Patient Educational Material for a Variant of Uncertain Significance (VUS) Result in Hereditary Cancer Genes.

A Variant of Uncertain Significance (VUS) is a difference in the DNA sequence with uncertain consequences for gene function. A VUS in a hereditary cancer gene should not change medical care, yet some patients undergo medical procedures based on their VUS result, highlighting the unmet educational needs among patients and healthcare providers. To address this need, we developed, evaluated, and refined novel educational materials to explain that while VUS results do not change medical care, it remains important to share any personal or family history of cancer with family members given that their personal and family medical history can guide their cancer risk management. We began by reviewing the prior literature and transcripts from interviews with six individuals with a VUS result to identify content and design considerations to incorporate into educational materials. We then gathered feedback to improve materials via a focus group of multidisciplinary experts and multiple rounds of semi-structured interviews with individuals with a VUS result. Themes for how to improve content, visuals, and usefulness were used to refine the materials. In the final round of interviews with an additional 10 individuals with a VUS result, materials were described as relatable, useful, factual, and easy to navigate, and also increased their understanding of cancer gene VUS results.

Inherited Cancer Knowledge Among Black Females with Breast Cancer Before and After Viewing a Web-Based Educational Video.

Purpose: Scalable solutions are needed to make pre-test genetic education about inherited cancer risk accessible across diverse and underserved populations. We evaluated an automated strategy to deliver genetic education through a web-based video among young Black females with breast cancer. Methods: 96 participants were recruited through state cancer registries in Florida and Tennesee. All participants viewed a 12 min video and completed a ten question quiz on inherited cancer knowledge before and after viewing the video. Median pre- and postvideo knowledge scores were categorized as <60% versus ≥60% and compared across demographic and clinical characteristics using binary logistic regression. Results: Of the 96 participants, mean age was 51, over 50% had income <$50 K, over 40% did not graduate college or have private insurance, and over 70% had previous genetic testing. Median knowledge scores significantly increased after viewing the video (p < 001), with no significant differences in those with or without prior testing. A higher post-video knowledge score was associated with an income ≥$50 K, a college degree, and private insurance (all p < .05). Conclusion: Among a population of young Black breast cancer patients, the educational video significantly increased knowledge. Findings support the use of automated pre-test educational tools as a scalable solution to make these services more accessible across populations.

Applying the framework for developing and evaluating complex interventions to increase family communication about hereditary cancer.

Objective: Evaluate an intervention to increase family communication (FC) of positive hereditary cancer test results using the Framework for Developing and Evaluating Complex Interventions (FDECI). Methods: We developed 'programme theory' during the FDECI development phase by aligning intervention components with behavior change techniques (BCTs) and theoretical factors expected to improve FC. During the feasibility phase, we obtained feedback from 12 stakeholder interviews. Results: Intervention components aligned with a total of 14 unique BCTs for which prior evidence links the BCT to theoretical factors that influence behavior change. Constructive stakeholder feedback included: more information desired, rewording to support autonomy by highlighting options, and improvements to navigation, visuals, and audio. Positive comments included: comprehensiveness of materials, modeling of conversations, and usefulness of the materials for helping a person prepare to share positive test results. Conclusion: The first FDECI phases were helpful for improving the intervention and planning our ongoing effectiveness and future implementation phases. Innovation: Our application of the FDECI is novel, including plans to test our 'programme theory' using coincidence analysis (CNA) to determine who accesses which intervention materials, how utilizing certain materials impact the aligned theoretical factors, and whether these in turn make a difference in the behavioral outcome.

Sharing genetic test results with family members of BRCA, PALB2, CHEK2, and ATM carriers.

OBJECTIVE: This study explored motivators and challenges/barriers to sharing personal genetic test results (GTR) with family members (FM). METHODS: Semi-structured, in-depth interviews were conducted with 62 women who had a pathogenic or likely pathogenic (P/LP) variant in aBRCA, PALB2, CHEK2, or ATM gene. Selective qualitative data analysis focused on eliciting motivators and challenges/barriers identified by participants when sharing their GTR with FM. RESULTS: Motivators to sharing personal GTR with FM included: health protection and prevention; moral obligation; decisional empowerment; familial ties; written resources; and contextualization for a familial cause for cancer. Challenges/barriers to family sharing included: concern for FM reactions; complexities of information; lack of closeness; perceived relevance; and emotional impact. CONCLUSIONS: All motivators and challenges/barriers were identified across BRCA and non-BRCA carriers, demonstrating commonalities in family sharing of GTR among high- to moderate-penetrance hereditary BC (breast cancer) genes. Despite challenges/barriers, participants disclosed their GTR with most close FM, yet restrictions in communication and/or strain on the timing, manner of disclosing, and strategies used varied across certain FM. PRACTICE IMPLICATIONS: These findings offer healthcare providers and researchers preliminary practical implications for broadly improving family sharing interventions across P/LP variants in BC risk genes by demonstrating important elements to include in family sharing letters.

Genetic Testing Across Young Hispanic and Non-Hispanic White Breast Cancer Survivors: Facilitators, Barriers, and Awareness of the Genetic Information Nondiscrimination Act.

AIMS: This study compared facilitators and barriers to genetic testing and determined awareness about the Genetic Information Nondiscrimination Act (GINA) across young Hispanic and non-Hispanic white (NHW) breast cancer (BC) survivors. MATERIALS AND METHODS: Women diagnosed with BC of age ≤50 years in 2009-2012 were recruited through the Florida State Cancer Registry to complete a questionnaire. RESULTS: There were 1182 participants of which 61% (174/285) of Hispanic patients, and 65% (580/897) of NHW patients had BC testing. Among untested participants, the most common barriers were lack of testing recommendation (44% Hispanics, 32% NHW; p = 0.02) and cost-related concerns (41% Hispanics, 40% NHW; p = 0.83). Among tested participants, the top facilitators were as follows: (1) "To benefit my family's future" (70% Hispanic, 68% NHW), (2) "My doctor recommended testing" (60% Hispanic, 54% NHW), and (3) "Minimal cost to me" (59% Hispanic, 72% NHW). Only 27% of tested and 15% of untested women were aware of GINA; misuse of test results was reported as a barrier for only 6.5%. CONCLUSIONS: Rates of genetic testing recommendation are lower among Hispanics, but both groups reported additional barriers. Most are unaware of GINA, yet misuse is not a highly cited barrier. Findings suggest the need to educate providers on the importance of recommending testing to all who meet criteria; increase awareness of newer options for more affordable testing; and bolster facilitators that may increase testing uptake.

Receipt of Bilateral Mastectomy Among Women With Hereditary Breast Cancer.

This case series study examines differences in surgical treatment among adult females with invasive breast cancer who have pathogenic or likely pathogenic variants in genes with high vs moderate breast cancer penetrance.

N1 and N2 ERPs reflect the regulation of automatic approach tendencies to positive stimuli.

The Approach-Avoidance Task (AAT) measures automatic approach-avoidance tendencies and their regulation: compatible reactions (approach positive, avoid negative) are faster than incompatible ones (approach negative, avoid positive). The present study assessed event-related potentials (ERPs) in 15 healthy persons for depicting neuropsychological sub-processes of such stimulus-response compatibility (SRC) effects. Early attention allocation preparing efficient stimulus classification (N1 ERP) and response inhibition on the level of response representations (N2 ERP) were found to underlie the solution of the AAT-conflict. For positive stimuli, these processes were enhanced during the incompatible condition avoid positive compared to the compatible condition approach positive. Source localization analysis revealed activity in right occipital areas (N1 ERP), and in left DLPFC and insula (N2 ERP) to be neuronal generators of these electrophysiological SRC effects. This neuronal regulation resulted in no influence of incompatibility at the behavioural level. For negative pictures, we found the reversed pattern: there were no electrophysiological SRC effects, but clear behavioural SRC effects in both RTs and error frequency, i.e. participants were faster and made fewer errors during avoiding than approaching negative pictures. These valence-specific differences are in line with previous studies indicating negative stimuli - probably due to higher importance for survival - to more strongly influence behaviour.

Controlled attention allocation mediates the relation between goal-oriented pursuit and approach-avoidance reactions to negative stimuli.

Approach and avoidance are two basic behavioural principles. The current study investigated neuropsychological mechanisms underlying the influence of the personality characteristic goal-oriented pursuit on the efficiency of regulating such approach-avoidance reactions. Therefore, the P3 event-related potential (ERP) reflecting controlled attention allocation was assessed during the Approach-Avoidance Task (AAT) with positive and negative pictures in 36 healthy participants. For negative pictures, analyses revealed the neuropsychological mechanism of controlled attention allocation to mediate the relation between personality and behaviour: Stronger goal-oriented pursuit was associated with higher controlled attention allocation to the incompatible compared to the compatible condition and--thereby--with less automatic avoidance tendencies in response to negative pictures, i.e., with higher efficiency of regulation. Results are discussed in terms of their implications for future studies on mechanisms determining the influence of personality traits, situational factors and their interaction on approach-avoidance behaviour.