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Introduction: When a pathogenic BRCA1 or BRCA2 mutation is identified in a family, cascade genetic testing of family members is recommended since the results may inform screening or treatment decisions in men and women. However, rates of cascade testing are low, and men are considerably less likely than women to pursue cascade testing. To facilitate cascade testing in men, we designed a Web-based genetic education tool that addressed barriers to cascade testing, was individually tailored, delivered proactively, and could be used in lieu of pretest genetic counseling to streamline the cascade testing process., Methods: We randomized 63 untested men from hereditary cancer families to Web-based genetic education (WGE) versus enhanced usual care (EUC). WGE participants were provided access to a genetic education website after which they could accept or decline genetic testing or opt for pretest genetic counseling. EUC participants received an informational brochure and a letter informing them of their eligibility for genetic testing and recommending they schedule genetic counseling. The primary outcome was the uptake of genetic testing., Results: Men in the WGE group were more likely to complete genetic counseling and/or genetic testing (43% vs. 12.1%; χ2 [n = 63, df = 1] = 7.77, p = 0.005). WGE participants were also more likely to complete genetic testing compared to men in the EUC group (30% vs. 9.1%; χ2 [n = 63, df = 1] = 4.46, p = 0.03)., Conclusion: This preliminary trial suggests that a streamlined approach to genetic testing using proactively delivered genetic education may reduce barriers to cascade testing for at-risk men, leading to increased uptake. These results should be interpreted cautiously given the select sample and high rate of non-response., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background and Objectives: Many newly diagnosed breast cancer patients do not receive genetic counseling and testing at the time of diagnosis. We examined predictors of genetic testing (GT) in this population., Methods: Within a randomized controlled trial of proactive rapid genetic counseling and testing vs usual care, patients completed a baseline survey within 6 weeks of breast cancer diagnosis but before a definitive survey. We conducted a multinomial logistic regression to identify predictors of GT timing/uptake., Results: Having discussed GT with a surgeon was a dominant predictor (χ 2 (2, N = 320) = 70.13; P < .0001). Among those who discussed GT with a surgeon, patients who had made a final surgery decision were less likely to receive GT before surgery compared with postsurgically (OR [odds ratio] = 0.24; 95% confidence interval [CI] = 0.12-0.49) or no testing (OR = 0.28; 95% CI = 0.14-0.56). Older patients (OR = 0.95; 95% CI = 0.91-0.99) and participants enrolled in New York/New Jersey (OR = 0.22; 95% CI = 0.07-0.72) were less likely to be tested compared with receiving results before surgery. Those with higher perceived risk (OR = 1.02; 95% CI = 1.00-1.03) were more likely to receive results before surgery than to not be tested., Conclusions: This study highlights the role of patient-physician communication about GT as well as patient-level factors that predict presurgical GT., (© 2020 Wiley Periodicals, Inc.)

Background: This study evaluates predictors of BRCA1/ 2 testing among breast and ovarian cancer survivors who received genetic counseling as part of a randomized trial and evaluates moderators of counseling mode on testing uptake. Methods: Predictors of BRCA1/2 testing within one year postcounseling were evaluated using multivariable logistic regression in a population-based sample of breast and ovarian cancer survivors at increased hereditary risk randomly assigned to in-person counseling (IPC; n = 379) versus telephone counseling (TC; n = 402). Variables that moderated the association between counseling mode and testing were identified by subgroup analysis. Results: Testing uptake was associated with higher perceived comparative mutation risk [OR = 1.32; 95% confidence interval (CI), 1.11-1.57] in the adjusted analysis. Those without cost barriers had higher testing uptake (OR = 18.73; 95% CI, 7.09-49.46). Psychologic distress and perceived comparative mutation risk moderated the effect of counseling and testing. Uptake between IPC versus TC did not differ at low levels of distress and risk, but differed at high distress (26.3% TC vs. 44.3% IPC) and high perceived comparative risk (33.9% TC vs. 50.5% IPC). Conclusions: Cost concerns are a strong determinant of testing. Differences in testing uptake by counseling mode may depend on precounseling distress and risk perceptions. Impact: Cost concerns may contribute to low testing in population-based samples of at-risk cancer survivors. Precounseling psychosocial characteristics should be considered when offering in-person versus telephone counseling. Cancer Epidemiol Biomarkers Prev; 26(12); 1772-80. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Practice guidelines incorporate genomic tumor profiling, using results such as the Oncotype DX Recurrence Score (RS), to refine recurrence risk estimates for the large proportion of breast cancer patients with early-stage, estrogen receptor-positive disease. We sought to understand the impact of receiving genomic recurrence risk estimates on breast cancer patients' well-being and the impact of these patient-reported outcomes on receipt of adjuvant chemotherapy. Participants were 193 women (mean age 57) newly diagnosed with early-stage breast cancer. Women were interviewed before and 2-3 weeks after receiving the RS result between 2011 and 2015. We assessed subsequent receipt of chemotherapy from chart review. After receiving their RS, perceived pros (t = 4.27, P < .001) and cons (t = 8.54, P < .001) of chemotherapy increased from pre-test to post-test, while perceived risk of breast cancer recurrence decreased (t = 2.90, P = .004). Women with high RS tumors were more likely to receive chemotherapy than women with low RS tumors (88 vs. 5 %, OR 0.01, 0.00-0.02, P < .001). Higher distress (OR 2.19, 95 % CI 1.05-4.57, P < .05) and lower perceived cons of chemotherapy (OR 0.50, 95 % CI 0.26-0.97, P < .05) also predicted receipt of chemotherapy. Distressed patients who saw few downsides of chemotherapy received this treatment. Clinicians should consider these factors when discussing chemotherapy with breast cancer patients., Competing Interests: The authors declare that they have no conflict of interest.

Purpose: As genetic counseling and testing become more fully integrated into clinical care, alternative delivery models are increasingly prominent. This study examines predictors of genetic testing for hereditary breast/ovarian cancer among high-risk women in a randomized trial of in-person versus telephone-based genetic counseling., Methods: Methods include multivariable logistic regression and interaction analyses., Results: Of the 669 participants, 600 completed counseling and 523 received test results. As previously reported, participants randomized to telephone counseling were significantly less likely to be tested. In intention-to-treat analyses, completion of counseling and testing was associated with: race/ethnicity (odds ratio (OR) = 1.96, 95% confidence interval (CI): 1.20-3.20), perceived stress (OR = 0.89, 95% CI: 0.81-0.98), knowledge (OR = 1.12, 95% CI: 1.02-1.23), and randomization group (OR = 1.48, 95% CI: 1.01-2.16). Further, race/ethnicity moderated the association between randomization group and testing; minority women receiving telephone counseling were least likely to complete testing., Conclusion: Evidence for logistical and communication-based explanations for this interaction is presented. The overall increased access made possible with telephone genetic counseling should be considered in light of the possibility that this may also lead to lower rates of testing among high-risk minority women. Additional care should be taken to assess and address potential barriers when services are delivered by telephone.Genet Med 17 6, 467-475.

Background: The growing demand for cancer genetic services underscores the need to consider approaches that enhance access and efficiency of genetic counseling. Telephone delivery of cancer genetic services may improve access to these services for individuals experiencing geographic (rural areas) and structural (travel time, transportation, childcare) barriers to access., Methods: This cluster-randomized clinical trial used population-based sampling of women at risk for BRCA1/2 mutations to compare telephone and in-person counseling for: 1) equivalency of testing uptake and 2) noninferiority of changes in psychosocial measures. Women 25 to 74 years of age with personal or family histories of breast or ovarian cancer and who were able to travel to one of 14 outreach clinics were invited to participate. Randomization was by family. Assessments were conducted at baseline one week after pretest and post-test counseling and at six months. Of the 988 women randomly assigned, 901 completed a follow-up assessment. Cluster bootstrap methods were used to estimate the 95% confidence interval (CI) for the difference between test uptake proportions, using a 10% equivalency margin. Differences in psychosocial outcomes for determining noninferiority were estimated using linear models together with one-sided 97.5% bootstrap CIs., Results: Uptake of BRCA1/2 testing was lower following telephone (21.8%) than in-person counseling (31.8%, difference = 10.2%, 95% CI = 3.9% to 16.3%; after imputation of missing data: difference = 9.2%, 95% CI = -0.1% to 24.6%). Telephone counseling fulfilled the criteria for noninferiority to in-person counseling for all measures., Conclusions: BRCA1/2 telephone counseling, although leading to lower testing uptake, appears to be safe and as effective as in-person counseling with regard to minimizing adverse psychological reactions, promoting informed decision making, and delivering patient-centered communication for both rural and urban women., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

This study examines communication about limitations of genomic results interpretation for colon cancer risk during education and counseling of minority participants. As part of a larger study conducted from 2010 to 2012, participants recruited from a large primary care clinic were offered testing for a research panel of 3 genomic markers (single nucleotide polymorphisms or SNPs) for colorectal cancer risk. Genetic counselors conducted pre- and post-test sessions which included discussion of limitations of result interpretation due to the lack of racial/ethnic diversity in research populations from which risk data are derived. Sessions were audio-recorded, transcribed and thematically analyzed. Many participants did not respond directly to this limitation. Among the participants that responded directly to this race-related limitation, many responses were negative. However, a few participants connected the limited minority information about SNPs with the importance of their current research participation. Genetic counselor discussions of this limitation were biomedically focused with limited explanations for the lacking data. The communication process themes identified included: low immediacy (infrequent use of language directly involving a participant), verbal dominance (greater speaking ratio of the counselor to the patient) and wide variation in the degree of interactivity (or the amount of turn-taking during the discussion). Placed within the larger literature on patient-provider communication, these present results provide insight into the dynamics surrounding race-related educational content for genomic testing and other emerging technologies. Clinicians may be better able to engage patients in the use of new genomic technology by increasing their awareness of specific communication processes and patterns during education or counseling sessions., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Purpose: Although guidelines recommend in-person counseling before BRCA1/BRCA2 gene testing, genetic counseling is increasingly offered by telephone. As genomic testing becomes more common, evaluating alternative delivery approaches becomes increasingly salient. We tested whether telephone delivery of BRCA1/2 genetic counseling was noninferior to in-person delivery., Patients and Methods: Participants (women age 21 to 85 years who did not have newly diagnosed or metastatic cancer and lived within a study site catchment area) were randomly assigned to usual care (UC; n = 334) or telephone counseling (TC; n = 335). UC participants received in-person pre- and post-test counseling; TC participants completed all counseling by telephone. Primary outcomes were knowledge, satisfaction, decision conflict, distress, and quality of life; secondary outcomes were equivalence of BRCA1/2 test uptake and costs of delivering TC versus UC., Results: TC was noninferior to UC on all primary outcomes. At 2 weeks after pretest counseling, knowledge (d = 0.03; lower bound of 97.5% CI, -0.61), perceived stress (d = -0.12; upper bound of 97.5% CI, 0.21), and satisfaction (d = -0.16; lower bound of 97.5% CI, -0.70) had group differences and confidence intervals that did not cross their 1-point noninferiority limits. Decision conflict (d = 1.1; upper bound of 97.5% CI, 3.3) and cancer distress (d = -1.6; upper bound of 97.5% CI, 0.27) did not cross their 4-point noninferiority limit. Results were comparable at 3 months. TC was not equivalent to UC on BRCA1/2 test uptake (UC, 90.1%; TC, 84.2%). TC yielded cost savings of $114 per patient., Conclusion: Genetic counseling can be effectively and efficiently delivered via telephone to increase access and decrease costs.

We conducted a translational genomic pilot study to evaluate the impact of genomic information related to colorectal cancer (CRC) risk on psychosocial, behavioral and communication outcomes. In 47 primary care participants, 96% opted for testing of three single nucleotide polymorphisms (SNPs) related to CRC risk. Participants averaged 2.5 of 6 possible SNP risk alleles (10% lifetime risk). At 3-months, participants did not report significant increases in cancer worry/distress; over half reported physical activity and dietary changes. SNP risk scores were unrelated to behavior change at 3-months. Many participants (64%) shared their SNP results, including 28% who shared results with a physician. In this pilot, genomic risk education, including discussion of other risk factors, appeared to impact patients' health behaviors, regardless of the level of SNP risk. Future work can compare risk education with and without SNP results to evaluate if SNP information adds value to existing approaches., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Numerous studies have documented the short-term impact of BRCA1/BRCA2 (BRCA1/2) testing; however, little research has examined the long-term impact of testing. We conducted the first long-term prospective study of psychosocial outcomes in a U.S. sample of women who had BRCA1/2 testing., Methods: Participants were 464 women who underwent genetic testing for BRCA1/2 mutations. Prior to testing, we measured sociodemographics, clinical variables, and cancer specific and general distress. At long-term follow-up (Median = 5.0 years; Range = 3.4-9.1 years), we assessed cancer-specific and genetic testing distress, perceived stress, and perceived cancer risk. We evaluated the impact of BRCA1/2 test result and risk-reducing surgery on long-term psychosocial outcomes., Results: Among participants who had been affected with breast or ovarian cancer, BRCA1/2 carriers reported higher genetic testing distress (β = 0.41, P < 0.0001), uncertainty (β = 0.18, P < 0.0001), and perceived stress (β = 0.17, P = 0.005) compared with women who received negative (i.e., uninformative) results. Among women unaffected with breast/ovarian cancer, BRCA1/2 carriers reported higher genetic testing distress (β = 0.39, P < 0.0001) and lower positive testing experiences (β = 0.25, P = 0.008) than women with negative results. Receipt of risk-reducing surgery was associated with lower perceived cancer risk (P < 0.0001)., Conclusions: In this first prospective long-term study in a U.S. sample, we found modestly increased distress in BRCA1/2 carriers compared with women who received uninformative or negative test results. Despite this modest increase in distress, we found no evidence of clinically significant dysfunction., Impact: Although a positive BRCA1/2 result remains salient among carriers years after testing, testing does not seem to impact long-term psychologic dysfunction., (©2012 AACR.)

Few studies have quantitatively evaluated the uptake and outcomes of BRCA1/2 genetic counseling and testing in men. We conducted a prospective longitudinal study to describe and compare uptake of and psychosocial outcomes following BRCA1/2 testing in a sample of men and women at high-risk for carrying a BRCA1/2 mutation. Men (n = 98) and women (n = 243) unaffected with cancer completed baseline assessments prior to genetic counseling and testing and then 6- and 12-months post-testing. Most men (n = 94; 95.9%) opted to have genetic testing, of whom 44 received positive BRCA1/2 genetic test results and 50 received true negative results. Among women, 93.4% had genetic testing, of whom 79 received positive results and 148 received negative results. In multivariate models, male BRCA1/2 carriers reported significantly higher genetic testing distress (6-months: Z = 4.48, P < 0.0001; 12-months: Z = 2.78, P < 0.01) than male non-carriers. After controlling for baseline levels of distress, no statistically significant differences emerged between male and female BRCA1/2 carriers in psychological distress at 12-months post-testing, although absolute differences were evident over time. Predictors of distress related to genetic testing among male carriers at 12-months included higher baseline cancer-specific distress (Z = 4.73, P < 0.0001) and being unmarried (Z = 2.18, P < 0.05). Similarly, baseline cancer-specific distress was independently associated with cancer-specific distress at 6- (Z = 3.66, P < 0.001) and 12-months (Z = 4.44, P < 0.0001) post-testing among male carriers. Clinically, our results suggest that pre-test assessment of distress and creation of educational materials specifically tailored to the needs and concerns of male carriers may be appropriate in this important but understudied high-risk group.

Women who receive positive or uninformative BRCA1/2 test results face a number of decisions about how to manage their cancer risk. The purpose of this study was to prospectively examine the effect of receiving a positive versus uninformative BRCA1/2 genetic test result on the perceived pros and cons of risk-reducing mastectomy (RRM) and risk-reducing oophorectomy (RRO) and breast cancer screening. We further examined how perceived pros and cons of surgery predict intention for and uptake of surgery. 308 women (146 positive, 162 uninformative) were included in RRM and breast cancer screening analyses. 276 women were included in RRO analyses. Participants completed questionnaires at pre-disclosure baseline and 1-, 6-, and 12-months post-disclosure. We used linear multiple regression to assess whether test result contributed to change in pros and cons and logistic regression to predict intentions and surgery uptake. Receipt of a positive BRCA1/2 test result predicted stronger pros for RRM and RRO (P < 0.001), but not perceived cons of RRM and RRO. Pros of surgery predicted RRM and RRO intentions in carriers and RRO intentions in uninformatives. Cons predicted RRM intentions in carriers. Pros and cons predicted carriers' RRO uptake in the year after testing (P < 0.001). Receipt of BRCA1/2 mutation test results impacts how carriers see the positive aspects of RRO and RRM and their surgical intentions. Both the positive and negative aspects predict uptake of surgery.

Objective: Few data are available regarding the long-term psychological impact of uninformative BRCA1/2 test results. This study examines change in distress from pretesting to 12-months post-disclosure, with medical, family history, and psychological variables, such as pretesting perceived risk of carrying a deleterious mutation prior to testing and primary and secondary appraisals, as predictors., Methods: Two hundred and nine women with uninformative BRCA1/2 test results completed questionnaires at pretesting and 1-, 6-, and 12-month post-disclosure, including measures of anxiety and depression, cancer-specific and genetic testing distress. We used a mixed models approach to predict change in post-disclosure distress., Results: Distress declined from pretesting to 1-month post-disclosure, but remained stable thereafter. Primary appraisals predicted all types of distress at 1-month post-disclosure. Primary and secondary appraisals predicted genetic testing distress at 1-month as well as change over time. Receiving a variant of uncertain clinical significance and entering testing with a high expectation for carrying a deleterious mutation predicted genetic testing distress that persisted through the year after testing., Conclusions: As a whole, women receiving uninformative BRCA1/2 test results are a resilient group. For some women, distress experienced in the month after testing does not dissipate. Variables, such as heightened pretesting perceived risk and cognitive appraisals, predict greater likelihood for sustained distress in this group and could be amenable to intervention.

Objective: Rising health disparities are increasingly evident in relation to use of genetic services (including genetic counseling and testing) for breast cancer risk, with women of African descent less likely to use genetic services compared with Whites. Meanwhile, little is known regarding potential within-group acculturation and psychological differences underlying perceived barriers to genetic testing among women of African descent., Methods: Hypothesized contributions of acculturation factors and breast cancer-specific distress to perceived barriers to genetic testing were examined with a statistical analysis of baseline data from 146 women of African descent (56% US born and 44% foreign born) meeting genetic breast cancer risk criteria and participating in a larger longitudinal study that included the opportunity for free genetic counseling and testing. Perceived barriers assessed included: (1) anticipation of negative emotional reactions, (2) stigma, (3) confidentiality concerns, (4) family-related worry, and (5) family-related guilt associated with genetic testing., Results: In multivariate analyses, being foreign born was a significant predictor of anticipated negative emotional reactions about genetic testing (beta=0.26; SE=0.11; p=0.01). Breast cancer-specific distress scores (avoidance symptoms) were positively related to anticipated negative emotional reactions (beta=0.02; SE=0.005; p=<0.0001), confidentiality concerns (beta=0.02; SE=0.01; p=0.02), and family-related guilt (beta=0.02; SE=0.01; p=0.0009) associated with genetic testing., Conclusions: Results suggest an influence of acculturation and breast cancer-specific distress on perceived barriers to genetic testing among women of African descent. The potential utility of culturally tailored genetic counseling services taking into account such influences and addressing emotional and psychological concerns of women considering genetic testing for breast cancer should be investigated.

Objective: To investigate high-risk breast cancer survivors' risk reduction decision making and decisional conflict after an uninformative BRCA1/2 test., Design: Prospective, longitudinal study of 182 probands undergoing BRCA1/2 testing, with assessments 1-, 6-, and 12-months postdisclosure., Measures: Primary predictors were health beliefs and emotional responses to testing assessed 1-month postdisclosure. Main outcomes included women's perception of whether they had made a final risk management decision (decision status) and decisional conflict related to this issue., Results: There were four patterns of decision making, depending on how long it took women to make a final decision and the stability of their decision status across assessments. Late decision makers and nondecision makers reported the highest decisional conflict; however, substantial numbers of women--even early and intermediate decision makers--reported elevated decisional conflict. Analyses predicting decisional conflict 1- and 12-months postdisclosure found that, after accounting for control variables and decision status, health beliefs and emotional factors predicted decisional conflict at different timepoints, with health beliefs more important 1 month after test disclosure and emotional factors more important 1 year later., Conclusion: Many of these women may benefit from decision making assistance., (Copyright 2009 APA, all rights reserved.)

Objective: Predictive genetic testing for hereditary breast/ovarian cancer risk (BRCA1/2 testing) is not recommended for minor children due to its lack of immediate medical benefit and potential psychological risk. Yet, tested mothers are often interested in learning about their children's cancer risks via pediatric BRCA1/2 testing, raising a host of bioethical concerns. However, no reliable or valid tool exists to formally gauge parents' interest in such testing. The aim of this study was to develop and evaluate a new measure for use in genetic research and consultation, known as the Pediatric BRCA1/2 Testing Attitudes Scale (P-TAS)., Methods: After pretest genetic counseling and provision of a blood sample for BRCA1/2 testing, the P-TAS was administered to 187 mothers of children between 8- and 21-years-old. The measure was also given to 96 of the mothers' nontested co-parents. Analyses of the factor structure and psychometric properties of the measure were performed in mothers and confirmed in their co-parents., Results: The two factors of the P-TAS, labeled Attitudes and Beliefs (Factor 1) and Decision Making and Communication (Factor 2), accounted for 62.9% of the variance and were reliable (Cronbach's coefficient alphas =.70 and .90, respectively); the structure and properties were largely confirmed among co-parents. Validity was indicated through its convergence with related constructs., Conclusions: This new tool may be integrated into genetic counseling research to better assess parents' attitudes and interests in pediatric BRCA1/2 testing. Such information may help guide ongoing discussions about the appropriateness of testing in adolescent or young adult children.

Objective: Genetic testing is increasingly part of routine clinical care for women with a family history of breast cancer. Given their substantially elevated risk for breast cancer, BRCA1/BRCA2 mutation carriers must make the difficult decision whether or not to opt for risk reducing mastectomy. To help BRCA1/2 carriers make this decision, the authors developed a computer-based interactive decision aid that was tested against usual care in a randomized controlled trial., Design: After the completion of genetic counseling, 214 female (aged 21-75) BRCA1/BRCA2 mutation carriers were randomized to Usual Care (UC; N = 114) or Usual Care plus Decision Aid (DA; N = 100) arms. UC participants received no additional intervention. DA participants were sent the CD-ROM DA to view at home., Main Outcome Measures: The authors measured final management decision, decisional conflict, decisional satisfaction, and receipt of risk reducing mastectomy at 1-, 6-, and 12-months postrandomization., Results: Longitudinal analyses revealed that the DA was effective among carriers who were initially undecided about how to manage their breast cancer risk. Within this group, the DA led to an increased likelihood of reaching a management decision (OR = 3.09, 95% CI = 1.62, 5.90; p < .001), decreased decisional conflict (B = -.46, z = -3.1, p <002), and increased satisfaction (B = .27, z = 3.1, p = .002) compared to UC. Among carriers who had already made a management decision by the time of randomization, the DA had no benefit relative to UC., Conclusion: These results demonstrate that BRCA1/BRCA2 mutation carriers who are having difficulty making a breast cancer risk management decision can benefit from adjunct decision support., ((c) 2009 APA, all rights reserved.)

The primary element involved in the practical delivery of hereditary cancer risk counseling is the development of a cancer genetics service. This service should involve a multidisciplinary core of specialists, aim to identify at-risk individuals and their families, and provide comprehensive genetic counseling with the option of genetic testing. This article examines the development of a cancer genetics service beginning with the fundamentals of patient ascertainment, location, staffing, and billing. It also reviews the elements involved in the provision of genetic counseling services, including formalized risk assessment and risk communication. Finally, we review novel modes of delivery of genetic counseling including the use of telephone counseling and telemedicine as a means of expanding the scope of this service and extending its reach to individuals who might otherwise not have access to a risk assessment clinic. Overall, this presentation can serve as a resource for identifying the practical aspects involved in the delivery of hereditary cancer risk counseling and their subsequent integration into the workings of a proficient cancer genetics service able to identify and serve at-risk patients and their family members.

Women who receive uninformative BRCA1/2 genetic test results face ongoing uncertainty about their future cancer risks. This article prospectively examined the influence of intolerance for uncertainty and perceived breast cancer risk on psychological distress following the receipt of uninformative BRCA1/2 test results. Sixty-four women who received uninformative BRCA1/2 mutation test results completed measures of Intolerance for Uncertainty, perceived breast cancer risk, and measures of cancer-related, genetic testing, and general distress. Cancer-related (DeltaR(2) = 0.18, P < or = 0.001), general (DeltaR(2) = 0.04, P < or = 0.05), and genetic testing distress (DeltaR(2) = 0.12, P < or = 0.01) were associated with intolerance for uncertainty at 1 month post-disclosure. The interaction of intolerance for uncertainty and breast cancer perceived risk predicted cancer-related (DeltaR(2) = 0.10, P < or = 0.001) and genetic testing distress (DeltaR(2) = 0.09, P < or = 0.01) at 6 months post-disclosure. Distress was highest among patients with highest perceived risk and intolerance for uncertainty, suggesting that those who have difficulty coping with their ambiguous risk are at risk for long-term distress. The clinical and research implications of these results are discussed., ((c) 2006 Wiley-Liss, Inc.)

Background: Among newly diagnosed breast cancer patients who are at risk for carrying a BRCA1 or BRCA2 mutation, knowledge of mutation status can influence local breast cancer treatment decisions. Thus, genetic testing at the time of diagnosis is increasingly considered an option for such patients. In this study, we evaluated factors associated with the decision to undergo BRCA1/BRCA2 gene testing at the time of initial breast cancer diagnosis., Methods: Participants were newly diagnosed breast cancer patients who had not yet received definitive local breast cancer treatment and who had a family history consistent with hereditary breast cancer. Participants were offered genetic counseling and BRCA1/BRCA2 testing with results in 2 to 3 weeks., Results: Of 231 patients who referred to the study, 20 (9%) declined the baseline interview, 34 (15%) completed a baseline interview but declined genetic testing, and 177 (76%) underwent BRCA1/BRCA2 testing. Physician recommendation for BRCA1/BRCA2 testing and indecision about definitive local treatment were both associated with undergoing testing. Among patients who were tested, 38 (21%) proceeded with definitive local treatment before receiving test results. Delay in the availability of test results and low levels of anxiety were associated with the decision to proceed with definitive local treatment before receiving test results., Conclusions: These results suggest that if rapid testing is available and genetic referrals are made for appropriate patients, a high proportion are likely to opt for such testing. In particular, patients who have not yet reached a decision about definitive local treatment may benefit from a genetic referral.

Background: Despite the potential importance of communication about genetic testing between test participants and their significant others, little is known about social support and communication between women undergoing BRCA1 and BRCA2 testing and their partners., Purpose: The aims of this longitudinal study were to examine communication about genetic testing during and following testing and to evaluate whether communication is associated with psychological distress reported by test participants and their partners., Methods: Participants were 153 women who were undergoing genetic testing and 118 partners of women undergoing testing. Relationship communication and distress were evaluated at the time of pretest education and 6 months postdisclosure., Results: Overall, the decision to undergo testing was discussed by the majority of test participants and partners, and most couples felt their partners were supportive. Most women disclosed their results to their partners. Longitudinal analyses suggested that less support and protective buffering were associated with greater distress 6 months postdisclosure among test participants, whereas lower comfort in sharing concerns and partner support were associated with lower distress 6 months postdisclosure among partners., Conclusions: The results of this study suggest that the majority of couples respond supportively during the test experience, but for a small subset of couples the process can strain the relationship. Partner support during this process is important, particularly for test participants dealing with an uninformative test result.

Purpose: Approximately 5% to 10% of newly diagnosed breast cancer patients carry a BRCA1 or BRCA2 mutation. Given these patients' high risk for contralateral breast cancer, bilateral mastectomy is increasingly considered a treatment option for newly diagnosed BRCA1/2 carriers. In the present study, we prospectively evaluated the impact on surgical decision-making of pretreatment genetic counseling and BRCA1/BRCA2 testing among breast cancer patients at high-risk for carrying a mutation., Patients and Methods: Participants were 194 newly diagnosed breast cancer patients who had not yet received definitive surgical treatment and who had at least a 10% prior probability of carrying a BRCA1/2 mutation. Participants were offered free genetic counseling and rapid BRCA1/2 testing. Primary analyses focused on the impact of BRCA1/2 test result on subsequent breast cancer surgical treatment., Results: Forty-eight percent of patients who were found to carry a BRCA1/2 mutation chose bilateral mastectomy as their definitive breast cancer surgery. In contrast, 24% of patients in whom no mutation was detected and 4% of test decliners opted for bilateral mastectomy. Additional predictors of bilateral mastectomy included patients' self-reports of physician recommendations for BRCA1/2 testing and bilateral mastectomy., Conclusion: This study highlights patient interest in and the technical feasibility of offering presurgery BRCA1/2 testing to high-risk patients. Most importantly, these results demonstrate that BRCA1/2 test results significantly affect patients' surgical decision-making. The availability of genetic counseling and testing could serve as a valuable aid to patient decision-making for newly diagnosed breast cancer patients at high-risk for carrying a mutation.

The Multidimensional Impact of Cancer Risk Assessment (MICRA) is a new tool to measure the specific impact of result disclosure after genetic testing. The authors compared its performance with that of questionnaires measuring general and cancer-specific distress. Participants (158 women) responded 1 month after they received genetic test results. The women were divided into 4 standard clinical test result groups: BRCA1/2 positive, BRCA1/2 negative, panel negative, and true negative. Factor analysis supported the formation of 3 subscales: Distress (6 items, alpha = .86), Uncertainty (9 items, alpha = .77), and Positive Experiences (4 items, alpha = .75). All 3 MICRA subscales differentiated participants who were BRCA1/2 positive from the other 3 groups. MICRA thus helps identify subgroups of vulnerable genetic testing participants.

We conducted a prospective, observational study to determine breast cancer screening practices among self-referred high-risk women who pursued genetic testing for BRCA1 and BRCA2 mutations. Of the 107 unaffected women included in this study, 41 were BRCA1/2 carriers and 66 women tested negative for a mutation previously identified in their family. All of the women underwent comprehensive pre- and posttest genetic counseling, and completed baseline and 12-month follow-up telephone interviews. The baseline (pretest) interview assessed potential predictors of mammography use, including demographics and psychosocial variables. During the year after the receipt of BRCA1/2 test results, 47% of the noncarriers and 59% of the carriers reported that they had had a mammogram [chi(2) (1, n = 107) = 1.35; P = 0.24]. Only 39% of carriers ages 25-39 reported having a mammogram, versus 74% of carriers age > or =40 [chi(2) (1, n = 41) = 5.10; P = 0.02]. Among noncarriers ages 50 and older, 83% had an annual mammogram. Factors independently associated with mammography use included age (<40, > or =40; odds ratio, 7.5; confidence interval, 2.6-21.5) and test result (odds ratio, 4.6; confidence interval, 1.1-18.7). The effects of perceived likelihood of having a BRCA1/2 gene alteration and the interaction between test result and perceived likelihood were not significant. As expected, most carriers (95%) and noncarriers (77%) obtained a clinical breast exam within the year after the receipt of test results. These data suggest that in carriers, overall, the use of breast cancer screening including mammography is good, although there was a relatively low uptake rate of mammography in younger carriers. Noncarriers had very good adherence to general population screening guidelines.

Purpose: Despite the increasingly widespread availability of BRCA1 and BRCA2 genetic testing, little is known about the psychologic impact of such testing in the clinical setting. The objective of this study was to examine the long-term psychologic impact of receiving BRCA1/2 test results within a clinic-based testing program., Patients and Methods: The participants were 279 high-risk women who underwent genetic counseling and testing for alterations in the BRCA1/2 genes. At baseline (before genetic testing) and at 6 months after the disclosure of mutation status, we measured perceived risk for breast and ovarian cancer, cancer-specific distress, and general distress. We examined the impact of the test result on each of these outcomes at the 6-month follow-up. Analyses were conducted separately for probands and their relatives who were unaffected with cancer., Results: We found no effect of test result among affected probands. Among unaffected relatives, we found that participants who received definitive negative test results exhibited significant reductions in perceived risk and distress compared with participants who received positive test results. Importantly, relatives who received positive test results did not exhibit increased distress or perceived risk., Conclusion: These results suggest that clinic-based BRCA1/2 testing can lead to psychologic benefits for individuals who receive negative test results. At 6 months after disclosure, those who receive positive or uninformative test results do not exhibit increased psychologic distress or perceived risk.

Stimulator of interferon genes (STING) is an intracellular sensor of cyclic di-nucleotides involved in the innate immune response against pathogen- or self-derived DNA. STING trafficking is tightly linked to its function, and its dysregulation can lead to disease. Here, we systematically characterize genes regulating STING trafficking and examine their impact on STING-mediated responses. Using proximity-ligation proteomics and genetic screens, we demonstrate that an endosomal sorting complex required for transport (ESCRT) complex containing HGS, VPS37A and UBAP1 promotes STING degradation, thereby terminating STING-mediated signaling. Mechanistically, STING oligomerization increases its ubiquitination by UBE2N, forming a platform for ESCRT recruitment at the endosome that terminates STING signaling via sorting in the lysosome. Finally, we show that expression of a UBAP1 mutant identified in patients with hereditary spastic paraplegia and associated with disrupted ESCRT function, increases steady-state STING-dependent type I IFN responses in healthy primary monocyte-derived dendritic cells and fibroblasts. Based on these findings, we propose that STING is subject to a tonic degradative flux and that the ESCRT complex acts as a homeostatic regulator of STING signaling. STING is an intracellular sensor of pathogen- or host-derived DNA. In this study, the authors identify an ESCRT complex that regulates STING degradation, thus acting as a homeostatic regulator of STING signalling and type-I interferon responses. [ABSTRACT FROM AUTHOR]

PURPOSE To evaluate timing and outcomes of BRCA testing and definitive surgical treatment among patients with newly diagnosed breast cancer. METHODS Patient-reported (n = 1,381) and deidentified health-plan (n = 2,369) data were analyzed from a consecutive national series of 3,750 women whose healthcare providers ordered BRCA testing between March 2014 and June 2015, within 1 year following breast cancer diagnosis. RESULTS Among 1,209 respondents, 54.4% received the genetic test results presurgery, 23.2% tested presurgery but received the results postsurgery, and 22.3% tested postsurgery. Patients aware of mutation-positive results presurgery were more likely to choose bilateral mastectomy (BLM) (n = 32/37) compared with patients who learned of positive results postsurgery (n = 14/32), (odds ratio [OR] = 8.23, 95% CI = 2.55 to 26.59, P, .001). When compared with women tested postsurgery, only women unaware of negative results presurgery had higher BLM rates (adjusted OR = 1.70, 95% CI = 1.07 to 2.69, P = .02). Among women > 50 tested presurgery, those unaware of negative results presurgery were more likely to choose BLM (n528/81) compared with those aware of negative results (n = 32/168) (OR = 2.25, 95% CI = 1.23 to 4.08, negative results awareness 3 age interaction, and P = .007). CONCLUSION Nearly half of participants did not receive BRCA results presurgery, which limited their ability tomake fully informed surgical treatment decisions. This may represent suboptimal care for unaware mutation-positive patients compared with those who were aware presurgery. Women > 50 who test negative are significantly less likely to choose BLM, a costly surgery that does not confer survival advantage, if they are aware of negative results presurgery. These results have important implications for quality of care and costs in the US health system. [ABSTRACT FROM AUTHOR]

Research to date regarding identification and management of hereditary breast and ovarian cancer syndrome (HBOC) in the U.S. has been confined primarily to academic center-based studies with limited patient engagement. To begin to understand and address the current gaps and disparities in delivery of services for the appropriate identification and optimal risk management of individuals with HBOC, we designed and have initiated the American BRCA Outcomes and Utilization of Testing (ABOUT) Study. ABOUT relies on a collaborative patient advocacy, academic and industry partnership to recruit and engage U.S. individuals who are at increased risk for HBOC and investigate their experiences, decisions and outcomes. It utilizes an extensive research infrastructure, including an interactive web-based data system and electronic interfaces for secure online participation and automated data exchange. We describe the novel recruitment approach that was designed for collaboration with a national commercial health plan partner to identify all individuals for whom a healthcare provider orders a BRCA test and mail to each individual an invitation to participate and study packet. The study packet contains detailed information about the study, a baseline questionnaire and informed consent for participation in the study, for release of relevant medical and health plan records and for ongoing research engagement. This approach employs patient-reported, laboratory-reported and health plan-reported outcomes and facilitates longitudinal engagement. We believe that the type of innovative methodology and collaborative framework we have developed for ABOUT is an ideal foundation for a patient-powered research network. This approach can make substantial contributions to identifying current and best practices in HBOC, leading to improved strategies for clinical care and optimal health outcomes among individuals with high inherited risk for cancer. [ABSTRACT FROM AUTHOR]

The authors comment on a report by J. L. Caswell-Jin et al on cascade testing in relatives at risk for hereditary cancer. Topics include benefits conferred by multigene cancer panel testing (MCPT) in relatives at risk for a familial pathogenic variant (PV), risks and limitations associated with MCPT, and public health impact of the implementation of cascade testing.

Genetic counseling and testing (GCT) informs risk reduction and management strategies in women at risk for carrying a pathogenic variation in the BRCA1 or BRCA2 (BRCA1/2) genes. African American (hereinafter referred to as Black) women are less likely to receive GCT services for hereditary breast and ovarian cancer (HBOC). The objective of this work was to examine existing literature regarding successful culturally tailored GCT interventions for Black women and to describe the rationale and protocol for a randomized feasibility trial to test the efficacy of a culturally tailored GCT intervention. The For Our Health (FOH) study is a two-arm randomized control trial designed to test the efficacy of a video intervention to promote the uptake of GCT among Black women with a high risk of HBOC. The culturally tailored video intervention targets key beliefs, knowledge gaps, misconceptions, and key anticipated emotions relevant for GCT. After completing the baseline survey, 50 women at risk of HBOC will be randomized (1:1) to one of two trial arms: a YouTube video intervention or a publicly available fact sheet. Final assessments will immediately follow receipt of either video or fact sheet. Few studies have tested interventions to improve GCT uptake among Black women. The FOH trial will fill an important scientific gap in knowledge regarding strategies to reduce disparities in GCT among Black women at risk of HBOC. [ABSTRACT FROM AUTHOR]

Purpose BRCA1/2 counseling and mutation testing is recommended for high-risk women, but geographic barriers exist, and no data on the costs and yields of diverse delivery approaches are available. Methods We performed an economic evaluation with a randomized clinical trial comparing telephone versus in-person counseling at 14 locations (nine geographically remote). Costs included fixed overhead, variable staff, and patient time costs; research costs were excluded. Outcomes included average per-person costs for pretest counseling; mutations detected; and overall counseling, testing, and disclosure. Sensitivity analyses were performed to assess the impact of uncertainty. Results In-person counseling was more costly per person counseled than was telephone counseling ($270 [range, $180 to $400] v $120 [range, $80 to $200], respectively). Counselors averaged 285 miles round-trip to deliver in-person counseling to the participants (three participants per session). There were no differences by arm in mutation detection rates (approximately 10%); therefore, telephone counseling was less costly per positive mutation detected than was in-person counseling ($37,160 [range, $36,080 to $38,920] v $40,330 [range, $38,010 to $43,870]). In-person counseling would only be less costly than telephone counseling if the most favorable assumptions were applied to in-person counseling and the least favorable assumptions were applied to telephone counseling. Conclusion In geographically underserved areas, telephone counseling is less costly than in-person counseling. [ABSTRACT FROM AUTHOR]