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.     

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.     

Psychological functioning in African American women at an increased risk of hereditary breast and ovarian cancer

Despite attention to psychological issues during genetic counselling and testing for hereditary breast and ovarian cancer risk, limited information is available on cancer-specific distress among African American women being targeted for participation in counselling and testing. Therefore, the purpose of this study is to examine cancer-specific distress in African American women at an increased risk of hereditary breast and ovarian cancer and to identify factors having significant associations with distress in this population. Respondents were 141 African American women identified for participation in genetic counselling and testing for BRCA1/2 mutations. Overall, respondents reported moderate levels of cancer-specific distress. Younger age (coefficient=6.0, p=0.001), being unemployed (coefficient=-5.0, p=0.01), and having a personal history of cancer (coefficient=5.0, p=0.02) had significant associations with intrusion. Younger age was also associated significantly with greater avoidance (r=6.0, p=0.02). These results suggest that African American women aged 50 and younger, those who are unemployed and women with a personal history of breast or ovarian cancer may be the most vulnerable to experiencing elevated levels of distress during genetic counselling and testing. Greater attention to psychological issues, including concerns about cancer and cancer risks, may be needed during genetic counselling and testing for BRCA1/2 mutations with these women.     

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.     

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.     

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.     

Physicians' attitudes towards mammography and prophylactic surgery for hereditary breast/ovarian cancer risk and subsequently published guidelines

After a BRCA mutation has been identified in the context of hereditary breast/ovarian cancer (HBOC), mammographic screening and prophylactic surgery are two of the main options available to those responsible for the clinical management of healthy women. The aim of this study was to describe the attitudes of specialists towards the clinical management of women with an HBOC risk: this information was collected prior to the publication of the recent French guidelines. A random national sample of 1169 French surgeons, gynaecologists and obstetricians was surveyed using a mailed questionnaire, to which 700 of these physicians (60%) responded. When dealing with a BRCA mutated woman, 88.6% of the respondents said they would recommend mammographic screening, but only 27.1% would recommend that it should be carried out annually from the age of 30 years onwards, as recommended in the French guidelines; 10.9% would find it acceptable to propose prophylactic mastectomy from the age of 30 years, and 22.9% would find it acceptable to propose prophylactic oophorectomy from the age of 35 years. The specialists who agreed with recommending breast/ovarian cancer genetic testing also had more positive attitudes towards prophylactic mastectomy (adj OR = 3.4, 95% CI = 1.4-8.2), as did those who had previously recommended prophylactic mastectomy when gene testing was not yet available (adj OR = 2.06, 95% CI = 1.23-3.44). The respondents' attitudes towards prophylactic oophorectomy and mastectomy were significantly associated (adj OR = 3.9; 95% CI = 2.3-6.5). Previous recommendation of prophylactic mastectomy was associated (P < 0.01) with a higher level of knowledge of breast/ovarian cancer genetics and with medical practice in this field. French physicians' attitudes towards mammographic screening and prophylactic surgery were not in complete agreement with the subsequently published French guidelines, the impact of which has now to be considered. Constantly evolving knowledge about the efficacy of preventive intervention will give practitioners new elements to integrate into their counselling.     

BRCA1/2 testing in hereditary breast and ovarian cancer families III: risk perception and screening

This study aimed to ascertain whether cancer risk perception changed following the offer and subsequent receipt of BRCA1/2 results and to evaluate breast and ovarian screening practices in testers and non-testers. Members of thirteen HBOC families were offered BRCA1/2 testing for a known family mutation. Perceived risk for developing breast cancer, ovarian cancer or for carrying the familial BRCA1/2 mutation, was assessed at baseline and again at 6-9 months following the receipt of test results. Breast and ovarian cancer screening data were obtained at both time-points. A total of 138 women participated and 120 (87%) chose to be tested for a known familial mutation. Twenty-eight women (24%) were identified as carriers and their perceived ovarian cancer risk and their perception of being a mutation carrier increased (P = 0.01 for both). Those testing negatives had a significant decrease in all dimensions of risk perception (P < 0.01). Regression analysis showed test results to be strong predictors of follow-up risk perception (P = 0.001), however, they were not predictors of screening practices at follow-up. Testers were more likely to have completed a clinical breast exam following testing than decliners. Mammography was positively associated with baseline adherence, age, and intrusive thoughts. Ovarian cancer worries only predicted pelvic ultrasound screening post-testing. Baseline practices and psychological factors appear to be stronger predictors of health behavior than test results.     

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.     

Colorectal cancer survivors undergoing genetic testing for hereditary non-polyposis colorectal cancer: motivational factors and psychosocial functioning

Hereditary non-polyposis colorectal cancer (HNPCC) represents about 1-3% of all cases of colorectal cancer (CRC). The objectives of the study were to examine motivational factors, expectations and psychosocial functioning in a sample of CRC survivors undergoing genetic testing for HNPCC. A cross-sectional survey of 314 colorectal cancer patients recruited through a population-based colon cancer family registry was conducted. Motivations for genetic testing for hereditary cancer were similar to those of clinic-based samples of CRC patients and included learning of the increased risk to offspring and finding out if additional screening was needed. While age at diagnosis and sex were associated with psychological functioning, significant predictors of post-counseling distress were perceived lower satisfaction with social support, an escape-avoidant coping style and the anticipation of becoming depressed if a mutation was present. Most cancer survivors anticipated disclosing test results to relatives and physicians. Cancer survivors reported several motivations for genetic testing for HNPCC that varied by sex. A subgroup of survivors with lower satisfaction with social support and an escape-avoidant coping style were worried about the potential impact of genetic test results and demonstrated more distress following counseling. Findings have implications for future research and potential support needs during the genetic counseling and testing process.     

Views of BRCA gene mutation carriers on preimplantation genetic diagnosis as a reproductive option for hereditary breast and ovarian cancer

BACKGROUND: In May 2006, the UK Human Fertilization and Embryology Authority (HFEA) approved use of preimplantation genetic diagnosis (PGD) for lower penetrance, late onset cancer susceptibility syndromes such as hereditary breast and ovarian cancer (HBOC). This is the first report on views of BRCA gene mutation carriers on use of PGD for HBOC. METHODS: Between December 2005 and February 2006, a postal survey of BRCA mutation carriers attending a Familial Cancer Clinic was undertaken. RESULTS: Of 102 women sent questionnaires, 52 (51%) responded. Thirty-nine (75%) felt it was acceptable to offer PGD for HBOC. Fifteen (37.5%) of 40 who had completed their families would personally have considered PGD if it had been available. Only one of seven (14%) contemplating a future pregnancy would consider PGD. Eighteen (35%) wrote extensively about their concerns including increasing availability of effective treatment and good quality of life. CONCLUSIONS: The majority of BRCA gene mutation carriers are supportive of offering PGD to others, thus endorsing the HFEA decision. However, most women would not consider it personally. Concerns raised highlight the need for regular HFEA reviews of the licensing criteria, as HBOC may cease to be a "serious life threatening illness" in the future.     

The molecular pathology of hereditary breast cancer: genetic testing and therapeutic implications.

Cancer arising in carriers of mutations in the BRCA1 and BRCA2 genes differs from sporadic breast cancer of age-matched controls and from non-BRCA1/2 familial breast carcinomas in its morphological, immunophenotypic and molecular characteristics. Most BRCA1 carcinomas have the basal cell phenotype, a subtype of high-grade, highly proliferating, estrogen receptor- and HER2-negative breast carcinomas, characterized by the expression of basal or myoepithelial markers such as basal keratins, P-cadherin, epidermal growth factor receptor, etc. This phenotype is rarely found in BRCA2 carcinomas, which are of higher grade than sporadic age-matched controls, but tend to be estrogen receptor- and progesterone receptor-positive. The expression of the cell-cycle proteins cyclins A, B1 and E and SKP2 is associated with a BRCA1 phenotype, whereas cyclin D1 and p27 expression is associated with BRCA2 carcinomas. Recent studies have shown that hereditary carcinomas that are not attributable to BRCA1/2 mutations have phenotypic similarities to BRCA2 tumors, but tend to be of lower grade and proliferation index. Somatic mutations in the BRCA genes are rarely found in hereditary tumors; by contrast, BRCA1 and BRCA2 loss of heterozygosity (LOH) is found in almost all BRCA1 and BRCA2 carcinomas, respectively. Furthermore, all types of hereditary breast carcinomas have a low frequency of HER2 expression. Finally, comparative genomic hybridization studies have revealed differences in chromosomal gains and losses between genotypes. The pathological and molecular features of hereditary breast cancer can drive specific treatments and influence the process of mutation screening. In addition, detecting molecular changes such as BRCA1/2 LOH in nonatypical cells obtained by random fine-needle aspiration, ductal lavage or nipple aspirate fluid may help to earlier identify carrier women who are at an even higher risk of developing breast carcinoma.     

Impact of direct-to-consumer advertising for hereditary breast cancer testing on genetic services at a managed care organization: a naturally-occurring experiment.

PURPOSE: To describe the impact of Myriad Genetics, Inc.'s direct-to-consumer advertising (DTC-ad) campaign on cancer genetic services within two Managed Care Organizations, Kaiser Permanente Colorado (KPCO), Denver, Colorado, where the ad campaign occurred, and Henry Ford Health System (HFHS), Detroit, Michigan, where there were no advertisements. METHODS: The main outcome measures were the changes in number and pretest mutation probability of referrals approved for cancer genetic services at KPCO and HFHS during the campaign versus the year prior, and mutation probability of those undergoing testing. RESULTS: At KPCO, referrals increased 244% during the DTC-ad compared to the same time period a year earlier (P value<0.001). The proportion of referrals at high pretest probability of a mutation (10% or greater) dropped from 69% the previous year to 48% during the campaign (P value<0.001). There was no significant change in pretest mutation probability among women who underwent testing between the two time periods. HFHS reported no significant change between the two time periods for numbers or mutation probability of referrals, or for mutation probability of women tested. CONCLUSION: The DTC-ad caused significant increase in demand for cancer genetic services. In the face of potential future DTC-ad for inherited cancer risk, providers and payers need to consider the delivery of genetic services and genetic education for persons of all risk levels.     

Communication with close and distant relatives in the context of genetic testing for hereditary breast and ovarian cancer in cancer patients

The psychological aspects of genetic testing for hereditary breast and ovarian cancer (HBOC) in cancer patients (diagnostic genetic testing) have so far received less attention than predictive genetic testing in unaffected persons. Our study is aimed at gaining insight into the psychological aspects of diagnostic genetic testing and at formulating practical recommendations for counseling. Cancer patients often play a key role in the communication of information to relatives because they were the first individuals to be tested in the family. The present article focuses on the communication to close and distant relatives about the hereditary cancer, the genetic test and its result. Participants previously diagnosed with breast and/or ovarian cancer, with a family history of these cancers and who requested DNA-testing, were eligible for the study. Of the 83 eligible patients who could be contacted, 63 participated (response rate = 76%). Twenty-six participants were members of a family where a BRCA1 or BRCA2 mutation was detected. The DNA-analysis in the family of 37 participants had not revealed any mutation. Data were collected by semi-structured interviews and psychological tests and questionnaires. The dissemination of information was largely focused on first-degree relatives. Communication to distant relatives about the genetic test and its result was problematic. Other than the genetic test result and age as "objective" predictors of informing distant relatives, little and/or superficial contact seemed to be the major subjective barrier to informing distant relatives. Furthermore, the knowledge about HBOC of these messengers reveals several shortcomings. Communication within the family should receive special attention during counseling.     

Communicating risk of hereditary breast and ovarian cancer with an interactive decision support tool

Objective

Women with hereditary breast and ovarian cancer syndrome (HBOC) face a higher risk of earlier, more aggressive cancer. Because of HBOC's rarity, screening is recommended only for women with strong cancer family histories. However, most patients do not have accurate history available and struggle to understand genetic concepts.

Methods

Cancer in the Family, an online clinical decision support tool, calculated women's HBOC risk and promoted shared patient–provider decisions about screening. A pilot evaluation (n = 9 providers, n = 48 patients) assessed the tool's impact on knowledge, attitudes, and screening decisions. Patients used the tool before wellness exams and completed three surveys. Providers accessed the tool during exams, completed exam checklists, and completed four surveys.

Results

Patients entered complete family histories (67%), calculated personal risk (96%), and shared risk printouts with providers (65%). HBOC knowledge increased dramatically for patients and providers, and many patients (75%) perceived tool results as valid. The tool prompted patient–provider discussions about HBOC risk and cancer family history (88%).

Conclusions

The tool was effective in increasing knowledge, collecting family history, and sparking patient–provider discussions about HBOC screening.

Practice implications

Interactive tools can effectively communicate personalized risk and promote shared decisions, but they are not a substitute for patient–provider discussions.     

Adverse childhood experiences of persons at risk for Huntington's disease or BRCA1/2 hereditary breast/ovarian cancer

Huntington's disease (HD) is known to have a negative impact on family life. Offspring of HD patients may be exposed to adversity in childhood because of the parent's disease and its psychological consequences. BRCA1/2 hereditary breast and ovarian cancer (BRCA1/2) increases the risk for offspring of being exposed to parental disease or loss. Childhood adversity is associated with psychopathology and various other problems in later life. Adverse childhood experiences (ACEs) before age 16 were assessed in adults at 50% risk for HD (n = 74) or BRCA1/2 (n = 82) and in controls (n = 101), using the Negative Life Events Scale. Mean number and occurrence of ACEs were compared between groups. The odds of having experienced adversity in childhood were higher in HD offspring and BRCA1/2 offspring than in controls. HD offspring reported a higher mean number of ACEs than controls or BRCA1/2 offspring. In HD offspring, the prevalence of parental disease and parental dysfunction experienced before age 16 was higher than in controls. In BRCA1/2 offspring, the prevalence of parental loss before age 16 was higher than in controls. This study indicates that 53% of HD offspring and 45% of BRCA1/2 offspring are exposed to adversity in childhood or adolescence. The relevance of these findings for counseling in predictive testing programs, reproductive decision-making, and child rearing matters is discussed.