Interest in genetic testing among first-degree relatives of breast cancer patients

The recent cloning of a breast-ovarian cancer susceptibility gene (BRCA1), and determination of the locus of a related gene (BRCA2), offers potential for clinical genetic testing for breast cancer susceptibility. This study examined interest in and expectations about an impending genetic test among first-degree relatives (FDRs) of breast cancer patients. One hundred five females completed two structured telephone interviews to assess demographics, breast cancer risk factors, psychological factors, and attitudes about genetic testing for breast cancer susceptibility. Overall, 91% of FDRs said that they would want to be tested, 4% said they would not, and 5% were uncertain. The most commonly cited reasons for wanting genetic testing were to learn about one's children's risk, to increase use of cancer screening tests, and to take better care of oneself. Women with less formal education were motivated by childbearing decisions and future planning to a greater degree than were women with education beyond high school. Most women anticipated a negative psychological impact of positive test results, involving increased anxiety (83%), depression (80%), and impaired quality of life (46%). In addition, 72% of women indicated that they would still worry if they tested negative. In multivariate regression analysis, level of baseline depression was the strongest predictor of an anticipated negative impact of genetic testing (Beta =.15; P,.0001). These results suggest that the demand for genetic testing for breast cancer susceptibility may be great, even among women who are not likely to have predisposing mutations. Prior to widespread availability of such testing, it will be critical to develop informed consent protocols to educate individuals about the benefits and limitations of predictive testing for this multifactorial disease. © 1995 Wiley-Liss, Inc.     

Acceptance of genetic testing for hereditary breast ovarian cancer among study enrollees from an African American kindred

Clinical availability of genetic testing for cancer predisposition genes is generating a major challenge for U.S. health care systems to provide relevant genetic services to underserved populations. Here we present rates of study enrollment and utilization of genetic testing in a research study on BRCA1 testing acceptance in one large kindred. We also present data on baseline access to genetic information as well as enabling and obstructing factors to study enrollment. The study population included female and male members of an African American kindred based in the rural southern United States with an identified BRCA1 mutation. A combination of quantitative and qualitative data were collected and analyzed. Of the 161 living, eligible, and locatable kindred members, 105 (65%) enrolled in the study. Family, personal, and educational motivations were the most commonly endorsed reasons for study participation. The most commonly cited reasons for refusal to participate in the study were: lack of interest, time constraints, and negative experiences with prior participation in genetic research. Eighty three percent of the participants underwent BRCA1 testing. In multiple logistic regression analysis, age 40-49 (odds ratio (OR) = 6.9; 95% confidence interval (CI) = 1.2-39.5), increased perceived risk of being a BRCA1 mutation carrier (OR = 4.1; 95% CI = 1.1-14.6), and high cancer genetics knowledge levels (OR = 1.5; 95% CI = 1.1-2.3) were associated with BRCA1 testing acceptance. The results of this study indicate that cognitive and demographic factors may influence genetic research participation and genetic testing decisions among African Americans who are at increased risk of carrying a deleterious BRCA1 mutation.     

Comparing family members' motivations and attitudes towards genetic testing for hereditary breast and ovarian cancer: a qualitative analysis

Genetic testing for hereditary breast and ovarian cancer reveals significant risk information regarding one''s chances of developing cancer that has potential implications for patients and their families. This study reports on the motivations and attitudes of index patients and their relatives towards genetic testing for hereditary breast and ovarian cancer. In total, 10 female index patients and 20 of their relatives were interviewed regarding their experiences of communicating genetic information within their families, and their motivations and attitudes towards genetic testing. The analysis found two types of ‘family groups'': groups strongly committed to genetic testing and groups uncertain about testing. Within committed family groups, index patients and their relatives felt obliged to be tested for others, leading some relatives to be tested without having fully thought through their decision or the implications of knowing their mutation status. These family groups also described considerations in relation to the value of testing for themselves. In family groups uncertain about testing, relatives had not attended for predictive testing, had postponed decision making until some point in the future or had expressed ambivalence about the value of testing for themselves. Results suggest the value of explicitly acknowledging motivations for genetic testing within the context of family obligations, relationships and communication, and the possible value of involving family members in genetic counselling and decision making from a family''s first contact with genetic services.     

Population-based genetic testing of asymptomatic women for breast and ovarian cancer susceptibility

PurposeThe identification of carriers of hereditary breast and ovarian cancer (HBOC) gene variants through family cancer history alone is suboptimal, and most population-based genetic testing studies have been limited to founder mutations in high-risk populations. Here, we determine the clinical utility of identifying actionable variants in a healthy cohort of women.MethodsGermline DNA from a subset of healthy Australian women participating in the lifepool project was screened using an 11-gene custom sequencing panel. Women with clinically actionable results were invited to attend a familial cancer clinic (FCC) for post-test genetic counseling and confirmatory testing. Outcomes measured included the prevalence of pathogenic variants, and the uptake rate of genetic counseling, risk reduction surgery, and cascade testing.ResultsThirty-eight of 5908 women (0.64%) carried a clinically actionable pathogenic variant. Forty-two percent of pathogenic variant carriers did not have a first-degree relative with breast or ovarian cancer and 89% pursued referral to an FCC. Forty-six percent (6/13) of eligible women pursued risk reduction surgery, and the uptake rate of cascade testing averaged 3.3 family members per index case.ConclusionWithin our cohort, HBOC genetic testing was well accepted, and the majority of high-risk gene carriers identified would not meet eligibility criteria for genetic testing based on their existing family history.     

Knowledge and attitudes of gynecologists regarding genetic counseling for hereditary breast and ovarian cancer

In a survey we investigated whether gynecologists are sufficiently knowledgeable to perform genetic counseling. It provides information for the development and evaluation of a counseling manual for professionals in primary health care. The members of the sample, consisting of 529 gynecologists in northern Germany, were mailed a questionnaire concerning their knowledge of and attitudes towards genetic counseling and testing for hereditary breast and ovarian cancer (HBOC). The response rate was 32.5% (n = 172). The majority of the respondents (82%) have received requests from patients for genetic testing. Most would offer basic genetic counseling to their patients, 66% feel knowledgeable enough to do so. Physicians set high value on communicating clinical management options, but also consider psychosocial aspects to be important. The results suggest that HBOC genetics play a noticeable role in the practice of gynecology in Germany. There is consensus about the need for further educational training to deal with cancer genetics in physicians' daily practice.     

Screening and genetic counselling for relatives of patients with breast cancer in a family cancer clinic.

Family history is the major risk factor in the aetiology of breast cancer. Breast screening is currently available to women from the age of 50 to 64 through the National Breast Screening Programme. There is, however, an equivalent risk of developing breast cancer below 50 for first degree relatives of women diagnosed with breast cancer premenopausally. We have estimated the risk of breast cancer for relatives of women affected at different ages and used these to establish a family cancer clinic offering breast screening based on individual risk. In three years we have seen 851 patients. Compliance for annual radiology was in excess of 83% over this period and of five cancers detected one had a lump at presentation, two developed interval breast lumps, and two were asymptomatic.     

Factors influencing intrafamilial communication of hereditary breast and ovarian cancer genetic information

What factors influence intrafamilial communication of hereditary breast and ovarian cancer (HBOC) genetic risk information? Such information can have health implications for individuals who undergo genetic testing, but it can also have implications for their blood relatives. This literature review adopts an ecological model to summarize factors at the individual, familial, and community levels, as well as cross cutting factors relating to the complexity of HBOC genetic information and responsibilities that this information can give rise to. These factors are complex and may result in conflicting senses of responsibility. Faced with the task of communicating HBOC genetic information, the response may be to attempt to balance the potential negative impact of the information on the well-being of the informee (eg, can s/he handle this information?) against the potential health benefit that the knowledge could result in. This balancing represents an effort to reconcile conflicting approaches to protecting family members, and is a moral dilemma. This review sheds light on the factors that contribute to resolve this dilemma.     

Surveillance behavior and prophylactic surgery after predictive testing for hereditary breast/ovarian cancer

This article describes breast or ovarian cancer surveillance practices and prophylactic surgery involving 34 carriers and 34 noncarriers of a BRCA1/2 mutation within the year after predictive testing. It also evaluates the effect of the predictive test result on cancer screening practices and provides insight into factors important in the decision-making process about health-related behavior. Within the year following predictive testing, 9% (3 of 34) of the carriers decided to have a prophylactic mastectomy. The majority of the carriers was adherent to recommendations regarding regular cancer surveillance following predictive testing. Furthermore, carriers' adherence to clinical breast examination and mammography recommendations significantly increased from pre- to posttest and was significantly higher than noncarriers' utilization after testing. Of the carriers eligible for prophylactic salpingo-oophorectomy, 75% had this operation. All carriers who were advised to have regular surveillance of the ovaries had ovarian ultrasounds. The authors gave major attention to factors playing a part in the decision-making process about health-related behavior.     

Attitudes about genetic testing and genetic testing intentions in African American women at increased risk for hereditary breast cancer.

PURPOSE: To evaluate attitudes about the benefits, limitations, and risks of genetic testing for BRCA1 and BRCA2 (BRCA1/2) mutations and explore testing intentions in African American women at increased risk for hereditary breast cancer. METHODS: Attitudes and intentions were evaluated by telephone in African American women (n = 74) at moderate and high risk for having a BRCA1/2 mutation. RESULTS: Attitudes about the benefits of genetic testing were endorsed at a higher rate relative to limitations and risks; however, only 30% of respondents indicated that they would definitely have testing. In regression analysis, women most likely to be considering testing were those with fatalistic beliefs about cancer and those who believed they had a BRCA1/2 mutation. Women who had two or more affected relatives were also most likely to be considering testing. Women who had a personal history of cancer and those who believed they were at high risk for developing breast cancer were most likely to report greater limitations and risks. Pros scores were higher among women older than age 50 and those who were unemployed. CONCLUSION: Although African American women at moderate and high risk for BRCA1/2 mutations report favorable attitudes about genetic testing, interest in testing may be limited. Women affected with cancer and those who believe they are at a higher risk for developing breast cancer may be most concerned about the negative consequences of testing. Increased attention may need to be given to beliefs about genetic testing and testing motivations during genetic counseling with African American women.     

Predictive testing for hereditary breast and ovarian cancer: a psychological framework for pre-test counselling

Since the identification of two breast-ovarian cancer susceptibility genes (BRCA1/2), predictive testing for hereditary breast/ovarian cancer (HBOC) has been available. Given the complexity and uncertainties of HBOC and the potential impact of predictive testing on psychological well-being, we offer the test applicants a combination of information-oriented and psychological counselling. In this paper, we describe the multidisciplinary approach for predictive testing for HBOC as a clinical service in Leuven, hereby focusing on psychological and decision counselling practice. Attention is paid to the theoretical framework used for pre-test psychological counselling in Leuven. We discuss three important interacting dimensions of psychological counselling: individual emotional support, decision counselling and support of the family communication process. Decision counselling consists of an evaluation of the cognitive and the emotional processing of the information given and strategies and resources for coping. This serves as a starting point to facilitate free informed decision making. Scenario development is used as a decision aid.     

Genetic counselling and testing for hereditary breast and ovarian cancer: the gent(le) approach

The counselling experience with 50 Flemish families in whom mutation analysis of the total coding region of the BRCA1 and BRCA2 gene has been initiated, is presented. Genetic testing for breast-ovarian cancer susceptibility is offered by a multidisciplinary team. During the counselling sessions, special attention is given to comprehensible and emotionally acceptable communication of genetic information and to the psychosocial evaluation of the counselee. The limitations of molecular testing and the controversy surrounding cancer prevention strategies are also discussed. The overall acceptance of mutation testing is high. Some of the problems encountered are inaccuracy of the reported family history, poor retrieval of the medical records of affected family members and the reluctance of many patients to inform their relatives about the possibility of being tested.     

Interest in genetic testing among affected men from hereditary prostate cancer families and their unaffected male relatives

PurposeThe objective of this study was to evaluate potential sociodemographic, medical, psychosocial, and behavioral correlates of interest in genetic testing in men from hereditary prostate cancer families.MethodsFamily members affected with prostate cancer (n = 559) and their unaffected male relatives (n = 370) completed a mailed survey. Multivariable logistic regression models were used to examine the association between potential correlates and interest in genetic testing for prostate cancer.ResultsForty-five percent of affected and 56% of unaffected men reported that they definitely would take a genetic test for prostate cancer. More affected men reported high levels of familiarity with genetic testing than unaffected men (46 vs. 25%). There were several variables that were significantly correlated with interest in either affected or unaffected men, but only age and familiarity with genetics were significant in both groups. After controlling for confounding variables, only familiarity remained a significant correlate in both groups.ConclusionsThe contrast between low levels of familiarity with genetics and high test interest among unaffected men highlights the need for increased educational efforts targeting hereditary prostate cancer families. Overall, results illuminated several novel characteristics of men from hereditary prostate cancer families that should be considered when developing future informed consent procedures or educational materials for prostate cancer genetic testing.     

Ethics of predictive DNA-testing for hereditary breast and ovarian cancer

The recent identification of gene mutations involved in hereditary cancers increasingly allows for predictive DNA-testing. There is an urgent need to analyse the ethical issues involved. This article concentrates on the ethics of predictive testing for mutations in the breast (and ovarian) cancer genes BRCA1 and -2. Using international guidelines for presymptomatic DNA-testing for Huntington disease and the Li-Fraumeni syndrome as a model, a provisional protocol, which entails four parts is presented: (i) inclusion and exclusion criteria; (ii) preparing for the test; (iii) informing about the results of the test; (iv) post-test counselling and evaluation. The importance of an integral education of both doctors and the public is stressed.     

Factors associated with preimplantation genetic diagnosis acceptance among women concerned about hereditary breast and ovarian cancer

PurposeTo assess sociodemographic, clinical, awareness, and attitudinal factors associated with acceptance of preimplantation genetic diagnosis among women concerned about hereditary breast and ovarian cancer.MethodsParticipants (n = 962) were members of a national advocacy organization dedicated to empowering women at high risk for developing breast or ovarian cancer. Participants completed a web-based survey assessing factors associated with preimplantation genetic diagnosis acceptance. Factors significantly associated with acceptance in the bivariate analyses were used to build a logistic regression model.ResultsAmong the 962 respondents, 318 (33.1%) selected the option that they would consider preimplantation genetic diagnosis, 367 (38.2%) would not consider preimplantation genetic diagnosis, and 277 (28.8%) selected “don't know.” Significant predictors of preimplantation genetic diagnosis acceptance were the desire to have more children, having had a prenatal genetic test, preimplantation genetic diagnosis awareness, belief that preimplantation genetic diagnosis is acceptable for individuals at risk for hereditary breast and ovarian cancer, belief that preimplantation genetic diagnosis information should be given to individuals at risk for hereditary breast and ovarian cancer, concerns about preimplantation genetic diagnosis, perceived benefits of preimplantation genetic diagnosis, and how preimplantation genetic diagnosis is considered.ConclusionWomen at increased risk for hereditary cancer may consider preimplantation genetic diagnosis as part of their reproductive decision making. Therefore, it is important to understand existing levels of awareness and attitudes toward this technology to provide optimal counseling and support.