Upgrade Rates and Breast Cancer Development Among Germline Pathogenic Variant Carriers with High-Risk Breast Lesions.

BACKGROUND: High-risk lesions (HRL) of the breast are risk factors for future breast cancer development and may be associated with a concurrent underlying malignancy when identified on needle biopsy; however, there are few data evaluating HRLs in carriers of germline pathogenic variants (PVs) in breast cancer predisposition genes. METHODS: We identified patients from two institutions with germline PVs in high- and moderate-penetrance breast cancer predisposition genes and an HRL in an intact breast, including atypical ductal hyperplasia (ADH), flat epithelial atypia (FEA), and lobular neoplasia (LN). We calculated upgrade rates at surgical excision and used Kaplan-Meier methods to characterize 3-year breast cancer risk in patients without upgrade. RESULTS: Of 117 lesions in 105 patients, 65 (55.6%) were ADH, 48 (41.0%) were LN, and 4 (3.4%) were FEA. Most PVs (83.8%) were in the BRCA1/2, CHEK2 and ATM genes. ADH and FEA were excised in most cases (87.1%), with upgrade rates of 11.8% (95% confidence interval [CI] 5.5-23.4%) and 0%, respectively. LN was selectively excised (53.8%); upgrade rate in the excision group was 4.8% (95% CI 0.8-22.7%), and with 20 months of median follow-up, no same-site cancers developed in the observation group. Among those not upgraded, the 3-year risk of breast cancer development was 13.1% (95% CI 6.3-26.3%), mostly estrogen receptor-positive (ER +) disease (89.5%). CONCLUSIONS: Upgrade rates for HRLs in patients with PVs in breast cancer predisposition genes appear similar to non-carriers. HRLs may be associated with increased short-term ER+ breast cancer risk in PV carriers, warranting strong consideration of surgical or chemoprevention therapies in this population.

Clinical tools and counseling considerations for breast cancer risk assessment and evaluation for hereditary cancer risk.

Breast cancer is a complex and heterogeneous disease. Unfortunately, it is the most common malignancy diagnosed in women in the USA, with 281,550 new cases of invasive breast cancer and 49,290 new cases of noninvasive breast cancer are diagnosed per year. In England, it is currently estimated that approximately 1 in 7 (14%) women will be diagnosed with breast cancer in their lifetime. In the UK in 2017, 54,700 women and 390 men were diagnosed with breast cancer. The risk of breast cancer is influenced by many factors, including but not limited to age, family history, reproductive history, hormonal exposure, proliferative breast lesions, physical activity, alcohol use, tobacco use, breast density, and environmental exposures. Breast cancer risk assessment is a critical part of public health. By identifying women at high risk for breast cancer, personalized recommendations can be deployed with regards to modes of screening, the age to initiate breast screening, and the frequency for completing such screens. In addition, breast cancer risk assessment can assist in determining a woman's eligibility for interventions to reduce risk, either through the use of chemoprevention medications or through surgical means with risk-reducing bilateral mastectomy. This chapter summarizes breast cancer risk assessment models and discusses interventions to reduce breast cancer risk to aid in reducing morbidity and mortality from breast cancer.

Implementation of INHERET, an Online Family History and Cancer Risk Interpretation Program for Primary Care and Specialty Clinics.

BACKGROUND: Individuals at increased risk for cancer are ascertained at low rates of 1% to 12% in primary care (PC). Underserved populations experience disparities of ascertainment, but data are lacking. INHERET is an online personal and family history tool to facilitate the identification of individuals who are eligible, according to guidelines, to be counseled on germline genetic testing and risk management. PATIENTS AND METHODS: INHERET data entry uses cancer genetics clinic questionnaires and algorithms that process patient data through NCCN Clinical Practice Guidelines in Oncology and best practice guidelines. The tool was tested in silico on simulated and retrospective patients and prospectively in a pilot implementation trial. Patients in cancer genetics and in PC clinics were invited to participate via email or a card. Informed consent was completed online. RESULTS: INHERET aimed to integrate patient data by algorithms based on professional and best practice guidelines to elicit succinct, actionable recommendations that providers can use without affecting clinic workflow or encounter length. INHERET requires a 4th-grade reading level, has simple navigation, and produces data lists and pedigree graphs. Prospective implementation testing revealed understandability of 90% to 100%, ease of use of 85%, and completion rates of 85% to 100%. Physicians using INHERET reported no added time to their encounters when patients were identified for counseling. In a specialty genetics clinic, INHERET's data were input, on average, within 72 hours compared with 4 to 6 weeks through standard care, and the queue for scheduling patients decreased from 400 to fewer than 15 in <6 months. CONCLUSIONS: INHERET was found to be accessible for all education and age levels, except patients aged >70 years, who encountered more technical difficulties. INHERET aided providers in conveying high-risk status to patients and eliciting appropriate referrals, and, in a specialty clinic, it produced improved workflows and shortened queues.

Genetic Literacy and Communication of Genetic Information in Families Concerned with Hereditary Breast and Ovarian Cancer: A Cross-Study Comparison in Two Countries and within a Timeframe of More Than 10 Years.

Examining genetic literacy in families concerned with hereditary breast and ovarian cancer (HBOC) helps understand how genetic information is passed on from individuals who had genetic counseling to their at-risk relatives. This cross-study comparison explored genetic literacy both at the individual and the family level using data collected from three sequential studies conducted in the U.S. and Switzerland over ≥10 years. Participants were primarily females, at-risk or confirmed carriers of HBOC-associated pathogenic variants, who had genetic counselling, and ≥1 of their relatives who did not. Fifteen items assessed genetic literacy. Among 1933 individuals from 518 families, 38.5% had genetic counselling and 61.5% did not. Although genetic literacy was higher among participants who had counselling, some risk factors were poorly understood. At the individual level, genetic literacy was associated with having counselling, ≤5 years ago, higher education, and family history of cancer. At the family level, genetic literacy was associated with having counselling, higher education, and a cancer diagnosis. The findings suggest that specific genetic information should be emphasized during consultations, and that at-risk relatives feel less informed about inherited cancer risk, even if information is shared within families. There is a need to increase access to genetic information among at-risk individuals.

Initial Findings from a High Genetic Risk Prostate Cancer Clinic.

OBJECTIVE: To improve prostate cancer screening for high-risk men, we developed an early detection clinic for patients at high genetic risk of developing prostate cancer. Despite the rapidly growing understanding of germline variants in driving aggressive prostate cancer and the increased availability of genetic testing, there is little evidence surrounding how best to screen these men. METHODS: We are reporting on the first 45 patients enrolled, men between the ages of 35-75, primarily with known pathogenic germline variants in prostate cancer susceptibility genes. Screening consists of an intake lifestyle survey, PSA, DRE, and SelectMDx urine assay. A biopsy was recommended for any of the following indications: 1) abnormal DRE, 2) PSA above threshold, or 3) SelectMDx above threshold. The primary outcomes were number needed to screen, and number needed to biopsy to diagnose a patient with prostate cancer. RESULTS: Patients enrolled in the clinic included those with BRCA1 (n=7), BRCA2 (n=16), Lynch Syndrome (n=6), and CHEK2 (n = 4) known pathogenic germline variants. The median age and PSA were 58 (range 35-71) and 1.4 ng/ml (range 0.1-11.4 ng/ml), respectively. 12 patients underwent a prostate needle biopsy and there were 4positive biopsies for prostate cancer. CONCLUSION: These early data support the feasibility of opening a dedicated clinic for men at high genetic risk of prostate cancer. This early report on the initial enrollment of our long-term study will help optimize early detection protocols and provide evidence for personalized prostate cancer screening in men with key pathogenic germline variants.

Genetic Testing and Surveillance of Young Breast Cancer Survivors and Blood Relatives: A Cluster Randomized Trial.

We compared a tailored and a targeted intervention designed to increase genetic testing, clinical breast exam (CBE), and mammography in young breast cancer survivors (YBCS) (diagnosed <45 years old) and their blood relatives. A two-arm cluster randomized trial recruited a random sample of YBCS from the Michigan cancer registry and up to two of their blood relatives. Participants were stratified according to race and randomly assigned as family units to the tailored (n = 637) or the targeted (n = 595) intervention. Approximately 40% of participants were Black. Based on intention-to-treat analyses, YBCS in the tailored arm reported higher self-efficacy for genetic services (p = 0.0205) at 8-months follow-up. Genetic testing increased approximately 5% for YBCS in the tailored and the targeted arm (p ≤ 0.001; p < 0.001) and for Black and White/Other YBCS (p < 0.001; p < 0.001). CBEs and mammograms increased significantly in both arms, 5% for YBCS and 10% for relatives and were similar for Blacks and White/Others. YBCS and relatives needing less support from providers reported significantly higher self-efficacy and intention for genetic testing and surveillance. Black participants reported significantly higher satisfaction and acceptability. Effects of these two low-resource interventions were comparable to previous studies. Materials are suitable for Black women at risk for hereditary breast/ovarian cancer (HBOC).

Splicing profile by capture RNA-seq identifies pathogenic germline variants in tumor suppressor genes.

Germline variants in tumor suppressor genes (TSGs) can result in RNA mis-splicing and predisposition to cancer. However, identification of variants that impact splicing remains a challenge, contributing to a substantial proportion of patients with suspected hereditary cancer syndromes remaining without a molecular diagnosis. To address this, we used capture RNA-sequencing (RNA-seq) to generate a splicing profile of 18 TSGs (APC, ATM, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, MLH1, MSH2, MSH6, MUTYH, NF1, PALB2, PMS2, PTEN, RAD51C, RAD51D, and TP53) in 345 whole-blood samples from healthy donors. We subsequently demonstrated that this approach can detect mis-splicing by comparing splicing profiles from the control dataset to profiles generated from whole blood of individuals previously identified with pathogenic germline splicing variants in these genes. To assess the utility of our TSG splicing profile to prospectively identify pathogenic splicing variants, we performed concurrent capture DNA and RNA-seq in a cohort of 1000 patients with suspected hereditary cancer syndromes. This approach improved the diagnostic yield in this cohort, resulting in a 9.1% relative increase in the detection of pathogenic variants, demonstrating the utility of performing simultaneous DNA and RNA genetic testing in a clinical context.

Genetic counseling and previvorship in patients with urologic malignancies.

PURPOSE OF REVIEW: With the increasing use of precision medicine in oncology, genetic counseling and germline genetic testing are becoming increasingly important in urologic malignancies. In this review, we summarize the most relevant recent literature regarding genetic counseling in prostate and kidney cancers. RECENT FINDINGS: Genetic counseling and testing is considered as an important component of workup for many patients with urologic malignancies but is likely underutilized. Genetic counseling in prostate cancer is a timely topic, especially as the demand for genetic counselors in oncology continues to increase with expanding guidelines for consideration of genetic testing. Genetic testing has historically been limited to only those with the most suspicious histories, but emerging data from larger studies indicates that the clinical presentation of inherited cancer syndromes are broader than previously appreciated. New models need to be developed for pretest counseling to meet increased demand. SUMMARY: Genetic counseling and testing will become increasingly important for patients with urologic malignancies. There is limited literature on this topic, especially related to kidney cancers. Further studies are needed to determine the best way to incorporate genetic counseling and testing into the care of these patients.

Evaluating and improving the implementation of a community-based hereditary cancer screening program.

Healthcare disparities exist in the provision of cancer genetic services including genetic counseling and testing related to BRCA1/2 mutations. To address this in a community health setting a screening tool was created to identify high-risk women. This study evaluates the implementation of the tool and identifies opportunities for improved cancer genetic screening, including regular clinician education. A mixed-method approach was used to evaluate clinician utilization of the screening tool at Planned Parenthood affiliates. Novel surveys that evaluated acceptance and implementation were administered to clinicians (n = 14) and semi-structured interviews (n = 6) were used to explore clinicians' perspectives and identify gaps in its utilization. Educational modules that addressed gaps were developed, implemented, and evaluated using a post-education survey (n = 8). Clinicians reported confidence in administering and interpreting the screening tool, but reported less confidence in their knowledge of cancer genetics and ability to connect clients with genetic counseling and testing (p = .003). Educational modules resulted in significant gains in clinician knowledge on genetic topics (p < .05) and increased self-reported confidence in connecting clients with genetic services. The modules reinforced the belief that genetic testing is beneficial for patients at increased risk (p = .001) and is important to inform subsequent medical management (p = .027). While building community clinicians' capacity to connect clients with genetic services is crucial, it is challenged by knowledge and confidence gaps in discussions of genetic services with clients. Consistent genetic-focused education with non-genetic clinicians can improve confidence and knowledge, enabling a more effective screening program in community health settings.

Disparities in genetic services utilization in a random sample of young breast cancer survivors.

PURPOSE: Increasing use of genetic services (counseling/testing) among young breast cancer survivors (YBCS) can help decrease breast cancer incidence and mortality. The study examined use of genetic services between Black and White/Other YBCS, attitudes and knowledge of breast cancer risk factors, and reasons for disparities in using genetic services. METHODS: We used baseline data from a randomized control trial including a population-based, stratified random sample of 3000 potentially eligible YBCS, with oversampling of Black YBCS. RESULTS: Among 883 YBCS (353 Black, 530 White/Other) were significant disparities between the two racial groups. More White/Other YBCS had received genetic counseling and had genetic testing than Blacks. Although White/Other YBCS resided farther away from board-certified genetic counseling centers, they had fewer barriers to access these services. Black race, high out-of-pocket costs, older age, and more years since diagnosis were negatively associated with use of genetic services. Black YBCS had lower knowledge of breast cancer risk factors. Higher education and genetic counseling were associated with higher genetic knowledge. CONCLUSION: Racial inequalities of cost-related access to care and education create disparities in genetic services utilization. System-based interventions that reduce socioeconomic disparities and empower YBCS with genetic knowledge, as well as physician referrals, can increase access to genetic services.

Development of a Web-based Family Intervention for BRCA Carriers and Their Biological Relatives: Acceptability, Feasibility, and Usability Study.

BACKGROUND: Carriers of breast cancer gene (BRCA) mutations are asked to communicate genetic test results to their biological relatives to increase awareness of cancer risk and promote use of genetic services. This process is highly variable from family to family. Interventions that support communication of genetic test results, coping, and offer decision support in families harboring a pathogenic variant may contribute to effective management of hereditary cancer. OBJECTIVE: The aim of this paper was to describe the development of the Family Gene Toolkit, a Web-based intervention targeting BRCA carriers and untested blood relatives, designed to enhance coping, family communication, and decision making. METHODS: We present findings from focus groups regarding intervention acceptability and participant satisfaction and from a pre-post pilot study with random allocation to a wait-listed control group regarding intervention feasibility and usability. RESULTS: The Family Gene Toolkit was developed by a multidisciplinary team as a psycho-educational and skills-building intervention. It includes two live webinar sessions and a follow-up phone call guided by a certified genetic counselor and a master's prepared oncology nurse. Each live webinar includes two modules (total four modules) presenting information about BRCA mutations, a decision aid for genetic testing, and two skill-building modules for effective coping and family communication. Participants in focus groups (n=11) were highly satisfied with the intervention, reporting it to be useful and describing clearly the important issues. From the 12 dyads recruited in the pre-post pilot study (response rate 12/52, 23%), completion rate was 71% (10/14) for intervention and 40% (4/10) for wait-listed control groups. CONCLUSIONS: Acceptability and satisfaction with the Family Gene Toolkit is high. On the basis of the findings from usability and feasibility testing, modifications on timing, delivery mode, and recruitment methods have been implemented. TRIAL REGISTRATION: ClinicalTrials.gov NCT02154633; https://clinicaltrials.gov/ct2/show/NCT02154633 (Archived by WebCite at http://www.webcitation.org/6yYNvLPjv).

Surveillance for cancer recurrence in long-term young breast cancer survivors randomly selected from a statewide cancer registry.

PURPOSE: This study examined clinical breast exam (CBE) and mammography surveillance in long-term young breast cancer survivors (YBCS) and identified barriers and facilitators to cancer surveillance practices. METHODS: Data collected with a self-administered survey from a statewide, randomly selected sample of YBCS diagnosed with invasive breast cancer or ductal carcinoma in situ younger than 45 years old, stratified by race (Black vs. White/Other). Multivariate logistic regression models identified predictors of annual CBEs and mammograms. RESULTS: Among 859 YBCS (n = 340 Black; n = 519 White/Other; mean age = 51.0 ± 5.9; diagnosed 11.0 ± 4.0 years ago), the majority (> 85%) reported an annual CBE and a mammogram. Black YBCS in the study were more likely to report lower rates of annual mammography and more barriers accessing care compared to White/Other YBCS. Having a routine source of care, confidence to use healthcare services, perceived expectations from family members and healthcare providers to engage in cancer surveillance, and motivation to comply with these expectations were significant predictors of having annual CBEs and annual mammograms. Cost-related lack of access to care was a significant barrier to annual mammograms. CONCLUSIONS: Routine source of post-treatment care facilitated breast cancer surveillance above national average rates. Persistent disparities regarding access to mammography surveillance were identified for Black YBCS, primarily due to lack of access to routine source of care and high out-of-pocket costs. IMPLICATIONS: Public health action targeting cancer surveillance in YBCS should ensure routine source of post-treatment care and address cost-related barriers. Clinical Trials Registration Number: NCT01612338.

Recruiting families at risk for hereditary breast and ovarian cancer from a statewide cancer registry: a methodological study.

PURPOSE: Cancer genetic services (counseling/testing) are recommended for women diagnosed with breast cancer younger than 45 years old (young breast cancer survivors-YBCS) and at-risk relatives. We present recruitment of YBCS, identification and recruitment of at-risk relatives, and YBCS willingness to contact their cancer-free, female relatives. METHODS: A random sample of 3,000 YBCS, stratified by race (Black vs. White/Other), was identified through a population-based cancer registry and recruited in a randomized trial designed to increase use of cancer genetic services. Baseline demographic, clinical, and family characteristics, and variables associated with the Theory of Planned Behavior (TPB) were assessed as predictors of YBCS' willingness to contact at-risk relatives. RESULTS: The 883 YBCS (33.2% response rate; 40% Black) who returned a survey had 1,875 at-risk relatives and were willing to contact 1,360 (72.5%). From 853 invited at-risk relatives (up to two relatives per YBCS), 442 responded (51.6% response rate). YBCS with larger families, with a previous diagnosis of depression, and motivated to comply with recommendations from family members were likely to contact a greater number of relatives. Black YBCS were more likely to contact younger relatives and those living further than 50 miles compared to White/Other YBCS. CONCLUSION: It is feasible to recruit diverse families at risk for hereditary cancer from a population-based cancer registry. This recruitment approach can be used as a paradigm for harmonizing processes and increasing internal and external validity of large-scale public health genomic initiatives in the era of precision medicine.

Updates on breast cancer genetics: Clinical implications of detecting syndromes of inherited increased susceptibility to breast cancer.

Since the initial discovery that pathogenic germline alterations in BRCA 1/2 increase susceptibility to breast and ovarian cancer, many additional genes have now been discovered that also increase breast cancer risk. Given that several more genes have now been implicated in hereditary breast cancer syndromes, there is increased clinical use of multigene panel testing to evaluate patients with a suspected genetic predisposition to breast cancer. While this is most certainly a cost-effective approach, broader testing strategies have resulted in a higher likelihood of identifying moderate-penetrance genes, for which management guidelines regarding breast cancer risk reduction have not been firmly established. In addition, the testing of more genes has led to increased detection of variants of uncertain significance. We review the current knowledge regarding both high- and moderate-risk hereditary breast cancer syndromes, as well as additional genes implicated in hereditary breast cancer for which there is limited data. Furthermore, strategies for cancer risk reduction in mutation carriers as well as therapeutic implications for those patients who harbor pathogenic germline alterations are discussed.

Use of Cancer Genetics Services in African-American Young Breast Cancer Survivors.

INTRODUCTION: African-American women have higher rates of early-onset breast cancer compared with their Caucasian counterparts; yet, when diagnosed with breast cancer at a young age, they underuse genetic counseling and testing to manage their risk of developing future cancers. METHODS: Self-reported baseline data were collected between September 2012 and January 2013 and analyzed in 2014 from a subpopulation of 340 African-American young breast cancer survivors (YBCSs) enrolled in an RCT. YBCSs were diagnosed with invasive breast cancer or ductal carcinoma in situ between ages 20 and 45 years and were randomly selected from a statewide cancer registry. Logistic regression examined predictors of using cancer genetics services. RESULTS: Overall, 28% of the sample reported having genetic counseling and 21% reported having genetic testing, which were significantly lower (p≤0.005) compared with white/other YBCSs participating in the parent study. In a multivariate analysis, income was positively associated with counseling (B=0.254, p≤0.01) and testing (B=0.297, p≤0.01), whereas higher education levels (B=-0.328, p≤0.05) and lack of access to healthcare services owing to cost (B=-1.10, p≤0.03) were negatively associated with genetic counseling. Lower income and lack of care because of high out-of-pocket costs were commonly reported barriers. CONCLUSIONS: Despite national recommendations for genetic evaluation among women with early-onset breast cancer, few African-American YBCSs reported undergoing genetic counseling and testing. Most reported that their healthcare provider did not recommend these services. Interventions addressing patient, provider, and structural healthcare system barriers to using genetic counseling and testing in this population are needed.

Using a state cancer registry to recruit young breast cancer survivors and high-risk relatives: protocol of a randomized trial testing the efficacy of a targeted versus a tailored intervention to increase breast cancer screening.

BACKGROUND: The Michigan Prevention Research Center, the University of Michigan Schools of Nursing, Public Health, and Medicine, and the Michigan Department of Community Health propose a multidisciplinary academic-clinical practice three-year project to increase breast cancer screening among young breast cancer survivors and their cancer-free female relatives at greatest risk for breast cancer. METHODS/DESIGN: The study has three specific aims: 1) Identify and survey 3,000 young breast cancer survivors (diagnosed at 20-45 years old) regarding their breast cancer screening utilization. 2) Identify and survey survivors' high-risk relatives regarding their breast cancer screening utilization. 3) Test two versions (Targeted vs. Enhanced Tailored) of an intervention to increase breast cancer screening among survivors and relatives. Following approval by human subjects review boards, 3,000 young breast cancer survivors will be identified through the Michigan Cancer Registry and mailed an invitation letter and a baseline survey. The baseline survey will obtain information on the survivors': a) current breast cancer screening status and use of genetic counseling; b) perceived barriers and facilitators to screening; c) family health history. Based on the family history information provided by survivors, we will identify up to two high-risk relatives per survivor. Young breast cancer survivors will be mailed consent forms and baseline surveys to distribute to their selected high-risk relatives. Relatives' baseline survey will obtain information on their: a) current breast cancer screening status and use of genetic counseling; and b) perceived barriers and facilitators to screening. Young breast cancer survivors and high-risk relatives will be randomized as a family unit to receive two versions of an intervention aiming to increase breast cancer screening and use of cancer genetic services. A follow-up survey will be mailed 9 months after the intervention to survivors and high-risk relatives to evaluate the efficacy of each intervention version on: a) use of breast cancer screening and genetic counseling; b) perceived barriers and facilitators to screening; c) self-efficacy in utilizing cancer genetic and screening services; d) family support related to screening; e) knowledge of breast cancer genetics; and f) satisfaction with the intervention. DISCUSSION: The study will enhance efforts of the state of Michigan surrounding cancer prevention, control, and public health genomics.

Individual and family characteristics associated with BRCA1/2 genetic testing in high-risk families.

BACKGROUND: Little is known about family members' interrelated decisions to seek genetic testing for breast cancer susceptibility. METHODS: The specific aims of this cross-sectional, descriptive, cohort study were (i) to examine whether individual and family characteristics have a direct effect on women's decisions to use genetic testing for hereditary susceptibility to breast cancer and (ii) to explore whether family characteristics moderate the relationships between individual characteristics and the decision to use genetic testing. Participants were women (>18 years old) who (i) received genetic testing for hereditary breast cancer and who agreed to invite one of their female relatives into the study and (ii) female relatives who had NOT obtained genetic testing and were identified by pedigree analysis as having >10% chances of hereditary susceptibility to breast cancer. RESULTS: The final sample consisted of 168 English-speaking, family dyads who completed self-administered, mailed surveys with validated instruments. Multivariate conditional logistic regression analyses showed that the proposed model explained 62% of the variance in genetic testing. The factors most significantly associated with genetic testing were having a personal history of cancer; perceiving genetic testing to have more benefits than barriers; having greater family hardiness; and perceiving fewer negative consequences associated with a breast cancer diagnosis. No significant interaction effects were observed. CONCLUSIONS: Findings suggest that both individual and family characteristics are associated with the decision to obtain genetic testing for hereditary breast cancer; hence, there is a need for interventions that foster a supportive family environment for patients and their high-risk relatives.

Differences between women who pursued genetic testing for hereditary breast and ovarian cancer and their at-risk relatives who did not.

PURPOSE/OBJECTIVES: To (a) examine differences in appraisals of hereditary breast and ovarian cancer (HBOC), psychological distress, family environment, and decisional conflict between women who pursued genetic testing and their at-risk relatives who did not, and (b) examine correlations among appraisals of HBOC, psychological distress, family environment, and decisional conflict regarding genetic testing in these two cohorts of women. DESIGN: Descriptive, cross-sectional cohort study. SETTING: Two clinics affiliated with a major research university in the midwestern United States. SAMPLE: 372 women aged 18 years and older. 200 pursued genetic testing for BRCA1 and BRCA2 mutations (probands) and 172 of their female relatives who had a greater than 10% prior probability of being a mutation carrier but had not pursued testing. METHODS: After providing informed consent, probands and relatives were mailed self-administered questionnaires. MAIN RESEARCH VARIABLES: Perceived risk, knowledge of HBOC risk factors and modes of gene inheritance, perceived severity, perceived controllability, psychological distress, family relationships, family communication, and decisional conflict about genetic testing. FINDINGS: T tests revealed that probands perceived higher risk and had more psychological distress associated with breast cancer. Probands had more knowledge regarding risk factors and gene inheritance, and greater decisional conflict regarding genetic testing. Relatives reported higher perceived severity and controllability. No differences were observed in family relationships and family communication between probands and relatives. Pearson correlations revealed different patterns in knowledge, perceived controllability, family relationships, and decisional conflict between probands and relatives. CONCLUSIONS: Significant differences exist between women who pursue genetic testing and those who do not. The family environment influences adjustment to HBOC and decisions about genetic testing. IMPLICATIONS FOR NURSING: Enhancing the family communication process about HBOC can provide informational and emotional support to high-risk women and promote decision making about genetic testing.