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© 1999 American Society for Clinical Oncology Attitudes, Knowledge, and Risk Perceptions of Women With Breast and/or Ovarian Cancer Considering Testing for BRCA1 and BRCA2From the Cancer Prevention, Detection, and Control Research Program and Department of Surgery, Duke University Medical Center; Institute of Statistics and Decision Sciences, Duke University, Durham, North Carolina; Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland; and Department of Care Coordination and Gillette Center for Women's Cancers, Dana-Farber Cancer Institute, Boston, Massachusetts. Address reprint requests to Leslie G. Bluman, MPH, Breast Oncology Center, Dana-Farber Cancer Institute, 44 Binney St, Boston, MA 02115.
PURPOSE: This study examined baseline knowledge, beliefs, and risk perceptions among a group of 200 women with breast and/or ovarian cancer who participated in a trial designed to improve decision making about genetic testing for BRCA1 and BRCA2. PATIENTS AND METHODS: Women were identified by self-referral, physician referral, and tumor registry extraction and invited to participate in a randomized trial in which testing for BRCA1 and BRCA2 was offered free of charge. Subjects completed baseline questionnaires and interviews that assessed knowledge, attitudes, and perceptions of risk of having an alteration in BRCA1 or BRCA2. RESULTS: Sixty percent of women overestimated their chances of having a BRCA1 or BRCA2 mutation compared with estimates from a BRCA1/BRCA2 risk model. Women who have at least three relatives with breast or ovarian cancer were one third (95% confidence interval, 0.2 to 0.6) as likely to overestimate their risk of having a BRCA1 or BRCA2 mutation compared with women who have two or fewer affected relatives. Knowledge was limited about BRCA1 and BRCA2 mutations and cancer risk associated with gene mutations. Eighty-four percent of the women indicated a probable or definite interest in testing. CONCLUSION: A high proportion of the high-risk women in this study had knowledge deficits about BRCA1 and BRCA2 and overestimated their risk of having a mutation. Although some degree of caution should be used in generalizing the results of this study to practice settings, the data provide insight into the challenges clinicians will face in communicating with patients about cancer genetics.
WITH THE DISCOVERY and cloning of BRCA1 and BRCA2,1,2 both enthusiasm and concern have been expressed about genetic testing. Testing for BRCA1 and BRCA2 is now clinically available at many medical centers. Preliminary studies among diverse segments of the population have shown considerable interest in genetic testing.3-8 Most professional organizations agree that the special nature of genetic information mandates close attention to the informed consent process and the information needs of women considering testing.9,10 Research reports to date show that knowledge levels about genetic testing for cancer susceptibility are suboptimal.11-14 People tend to overemphasize the benefits of testing and downplay the risks and limitations.11-13,15 There is uncertainty about many facets of testing, including the cancer risks associated with different mutations and the effectiveness of interventions (eg, intensive screening, surgeries) for reducing risk. Thus, achieving informed consent may be particularly difficult.16,17 A better understanding of what elements are involved in decision making about genetic testing is needed to develop, evaluate, and improve informed consent strategies for genetic testing for cancer susceptibility. Although a number of studies have focused on women's perceptions of their risk of developing breast cancer in their lifetime,5,18-24 fewer have examined women's perceptions of the risk of having a mutation in BRCA1 or BRCA24,25 and how those perceptions may contribute to decisions about testing. Inaccurate perceptions of the risk of having an altered BRCA1 or BRCA2 gene and of personal cancer risk may interfere with informed consent. Lloyd and colleagues24 found that a large proportion of their controls (women who did not receive special information about their risk) substantially overestimated their risk. On the other hand, overestimation was reduced in women who were given individualized risk estimates. When considering the likelihood of having an altered cancer susceptibility gene, women from high-risk breast and ovarian cancer families frequently report a belief that having a mutation is nearly certain.26 This report presents data from the baseline survey of a randomized trial designed to improve decision making about genetic testing among women with a history of breast and/or ovarian cancer and their high-risk relatives. The results presented here are for affected women only, those who have had breast and/or ovarian cancer. Although there may be greater interest in the decision-making process for unaffected women, women with a personal history of breast and/or ovarian cancer are generally the first members of a family to be tested in most genetic testing programs. We examined women's pretest knowledge, attitudes, information preferences, and perceptions of risk of having a BRCA1 or BRCA2 mutation. We independently compared women's estimates of BRCA1 and BRCA2 mutation risk with those generated by a BRCA1 and BRCA2 statistical risk model.
Subjects Potential subjects with a personal history of breast and/or ovarian cancer were identified by self-referral, physician referral, and Duke University and Presbyterian Hospital tumor registries. They received a mailed introductory letter followed by a telephone-administered family history survey. Responses from this survey were coded, entered into the Duke Family Cancer Program database, and imported into Cyrillic 2.1 (Cherwell Scientific, Palo Alto, CA), a program designed to generate pedigrees. For each potential subject, the probability of being a BRCA1 or BRCA2 mutation carrier was assessed by BRCAPRO.27 These estimates were categorized into quartiles (  25%, 26% to 50%, 51% to 75%,  76%). Eligible women (as determined by the eligibility criteria listed in Table 1) were sent an invitation and consent form for the randomized study that offered testing for BRCA1 and BRCA2 free of charge, request forms for confirmation of cancer diagnoses, and a self-administered baseline questionnaire along with an addressed stamped envelope. Three hundred thirty-one probands with a history of breast and/or ovarian cancer and with a family history of breast and/or ovarian cancer were invited to participate in the study as of January 12, 1998; of those invited, 208 had completed and returned baseline questionnaires by February 11, 1998. The mean time from survey mailing to survey receipt was 25 days, with a maximum of 231 days. Thus, some of the nonresponders at the time of analysis may eventually respond. Women who were subsequently found to have lobular carcinoma in situ (n = 5) and those with incomplete data (n = 3) were excluded from these analyses, resulting in a sample size of 200.
Measures
Pros and cons of genetic testing: A series of 16 Likert-style items, adapted from the series used by Lerman and colleagues,5 was developed to assess attitudes about pros and cons of genetic testing. Measures of attitudes and expectations about BRCA1 and BRCA2 testing were developed, and a majority of these items were validated in recent research by Lerman and colleagues (Cronbach's alpha coefficients, 0.73 [six pro items] and 0.85 [six con items]).4,5 This measure is based on decision-making theory and research28,29 and has been shown to predict a variety of health behaviors. Risk perceptions: Two items were adapted from previous research15 to assess perceived absolute risk of having an altered BRCA1 or BRCA2 gene. Knowledge and attitudes about BRCA1 and BRCA2: A 13-item "true or false" measure, adapted from that used previously by Lerman and colleagues,11,31 was included to assess knowledge of inheritance of breast and ovarian cancer predisposition, effect of having an altered gene, and related information. Center for Epidemiologic Studies Depression Scale (CES-D): The CES-D is a 20-item, multidimensional symptom rating scale that measures depressive symptomology.32 Alpha coefficients of internal consistency of 0.85 and 0.87 in community populations have been reported, suggesting excellent reliability. BRCA1 and BRCA2 testing plans and future decision: We evaluated women's readiness for testing based on self-reported intentions for BRCA1 and BRCA2 testing.4,30,33 The following response choices were presented: (1) definitely will not be tested, (2) probably will not be tested, (3) considering testing but still unsure, (4) probably will be tested, (5) definitely will be tested, and (6) have not yet considered testing. Risk estimates determined by the BRCAPRO model: The probability model used in this study evaluates the chance that the proband carries a mutation in BRCA1 or BRCA2.27,34 This model assumes autosomal dominant inheritance of mutations and has been shown to be highly predictive of carrier status.35-37 It incorporates information about the following: proband and her first- and second-degree relatives, relatives with no disease, ovarian cancer of probands and her relatives, relatives with both breast and ovarian cancer, bilateral breast cancer (synchronous or not), ages at diagnosis or ages at death of proband and her relatives, male breast cancer, outcome of genetic testing in any members of the family, and ethnicity (Ashkenazi Jewish or not). Pairwise comparisons were made between subjects' risk estimates and those generated by the model. Model estimates were categorized into quartiles to allow for comparisons to be made with subject estimates.
Data Management and Statistical Analyses
Demographics Characteristics of the study population are listed in Table 2. The vast majority of participants were white (94%), married (78%), and college educated (55%). Similarly, most of the nonresponders were white (89%). The mean age of participants was 49 years, and the mean age of nonresponders was 50 years. Most of the responders had a personal history of breast cancer (91%); nonresponders were more likely to have had a personal history of ovarian cancer (17% v 7%). The mean time since the most recent diagnosis among responders was 7 years, and there was no significant difference between the two groups. The average risk of being a BRCA1 or BRCA2 mutation carrier (as determined by BRCAPRO) was not significantly different between the responders and nonresponders. The values were 36% and 34% among responders and nonresponders, respectively.
Knowledge About BRCA1 and BRCA2
Medical Decision Making and Interest in Testing The vast majority (84%) of women said that they would probably or definitely be tested, citing a number of potential benefits: to provide advantages for their families (92%), to help their children (83%), to be reassured if the results were negative (73%), to take steps to prevent cancer (73%), to plan better for the future (63%), and to decrease anxiety (58%). The most important potential disadvantage was worry or uncertainty about the effect of testing on insurance, which was cited by 46% of women. Although there was no association between a woman's interest in testing and the model risk estimate (by quartile), there was a significant association between interest in testing and the subject's own risk assessment (by quartile). Of note, all participants were offered testing free of charge. Table 4 lists the results of logistic regression modeling for the predictors of definite interest in testing. Women who had been advised by their doctors to be tested were two times (95% confidence interval [CI], 1.1 to 3.7) more likely to express definite interest in BRCA1 and BRCA2 testing. In addition, women with a higher perceived risk quartile were more likely to express definite interest in testing (odds ratio, 1.5; 95% CI, 1.1 to 2.0).
Women's Risk Estimates Versus Model Risk Estimates
Figure 3 plots women's estimates of being BRCA1 or BRCA2 carriers compared with their corresponding BRCAPRO model estimates. When compared with the model assessments, more than 75% of women overestimated their risk, and approximately 25% underestimated their risk. There was variability in the degree to which women overestimated their risks. For example, for a woman who estimated her probability to be 50%, the average model probability (according to the regression) was 29%. For a woman who estimated her risk to be 100%, the average model probability was only 48%. The average difference between the women's estimates and the model estimates was 32%.
Predictors/Correlates of Overestimation of Risk
In interpreting the results of our study, the limitations should be considered. First, participation was voluntary, and the fact that testing was free may have resulted in certain selection biases. Second, all the patients included in this analysis were affected with breast and/or ovarian cancer. A personal history of cancer undoubtedly affects risk perceptions and may have an impact on intentions to be tested. For example, some of these women already have faced problems with insurance as a result of their cancer diagnoses and thus may have had less concern about insurance discrimination as a result of testing. The homogeneous nature of the population, particularly with respect to ethnicity, limits the generalizability of the results to a more ethnically diverse population. Finally, the study methods are not completely representative of clinical practice. Although women could self-refer to the project, the majority of women were recruited through proactive methods. The majority of our subjects, all of whom had a personal history of breast and/or ovarian cancer and were enrolled in a comprehensive cancer center–based BRCA1 and BRCA2 counseling study, intended to have genetic testing for BRCA1 and BRCA2 mutations. Overall, 84% of the women indicated that they would probably or definitely undergo testing. This finding is generally consistent with several other studies of interest in cancer susceptibility gene testing, which have found 75% or more of high-risk family members to be interested in testing for BRCA1 and BRCA2 mutations.4-6 In fact, of the 142 women in this sample who attended pretest counseling, 134 (94%) sought testing. This latter number is higher than the studies reported to date and may, in part, have been due to the offer of free testing. Our results add to the growing body of evidence indicating that women overestimate their chances of having BRCA1 or BRCA2 mutations24 and lack basic knowledge about cancer genetics. Women's knowledge deficits in our sample closely parallel those among the high-risk unaffected women studied by Lerman et al.31 These issues are of great concern. An informed decision should reflect the risks and benefits of genetic testing39 and a realistic appraisal of one's individual probability of having a mutation. As discussed by Croyle and Lerman,40 perceived susceptibility has been shown to predict actual participation in genetic testing. For some women, a more realistic and accurate perception of the risk of having a BRCA1 or BRCA2 mutation might make them less interested in genetic testing; for others, it might have the opposite effect. There is no "right" answer for all women. Our concern is to maximize the decision-making process for individuals. Lerman et al15 found that two thirds of women who received risk counseling continued to overestimate their risk of developing breast cancer. Although accurate risk perceptions are almost certainly important, they are only one factor in decision making. Consistent with other areas of testing in cancer,41 women in this study were more likely to be interested in testing if advised by their physicians. It is important that physicians educate patients about genetic risks and provide other relevant information about genetic testing in order to promote informed decisions. Some physicians may benefit from continuing education in the area of genetics.42,43 Such education should include a practical focus on doctor-patient communication about genetic testing and should also cover guidelines for recommending testing. Because our results confirm previous research showing that women tend to focus on the benefits of testing and downplay the potential limitations,11-13,15 it is particularly important that physicians have a clear understanding of the benefits, limitations, and risks of testing and be comfortable in communicating this information to their patients. Overestimation of risk was not predicted by age, race, or previous testing in a family member. However, women with three or more first- and second-degree relatives diagnosed with breast or ovarian cancer were less likely to overestimate their risk of having a BRCA1 or BRCA2 mutation. Because women with fewer affected relatives were more likely to overestimate their risk, they may benefit from education about how family history affects risk and should be cautioned about the need and/or value of testing. In view of the high proportion of women who overestimate their chances of having a BRCA1 or BRCA2 mutation, future studies should address the impact of providing accurate risk assessments along with other information generally included in pretest counseling. In the meantime, health care providers should be aware that many women overestimate their risk of having mutations. By providing accurate risk estimates along with other information considered central to informed consent (eg, a description of the test, risks and benefits of testing, confidentiality issues, and cost), patients should be better able to make informed decisions about genetic testing. As in a growing number of areas of medicine, there are no right or wrong decisions, only best choices for individuals. In areas such as genetic testing for which the benefits of an intervention are not clear, informed decisions are essential.
Supported by Duke SPORE (Specialized Program of Research Excellence) in Breast Cancer, National Institutes of Health grant no. CA 68438. We are grateful to Caryn Lerman, PhD, for sharing her instruments and for sage advice on many aspects of this project. We thank the many women who are in the study for their willingness to provide data.
1. Miki Y, Swensen J, Shattuck-Eidens D, et al: A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 266:66-71, 1994 2. Wooster R, Bignell G, Lancaster J, et al: Identification of the cancer susceptibility gene BRCA2. Nature 378:789-792, 1995[Medline] 3. Croyle RT, Lerman C: Interest in genetic testing for colon cancer susceptibility: Cognitive and emotional correlates. Prev Med 22:284-292, 1993[Medline] 4. Lerman C, Daly M, Masny A, et al: Attitudes about genetic testing for breast-ovarian cancer susceptibility. J Clin Oncol 12:843-850, 1994[Abstract] 5. Lerman C, Seay J, Balshem A, et al: Interest in genetic testing among first-degree relatives of breast cancer patients. Am J Med Genet 57:385-392, 1995[Medline] 6. Struewing JP, Lerman C, Kase RG, et al: Anticipated uptake and impact of genetic testing in hereditary breast and ovarian cancer families. Cancer Epidemiol Biomarkers Prev 4:169-173, 1995[Abstract]
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Lerman C, Narod S, Schulman K, et al: BRCA1 testing in families with hereditary breast-ovarian cancer: A prospective study of patient decision making and outcomes. JAMA 275:1885-1892, 1996 12. Wonderlick AL, Fine BA: Knowledge of breast cancer genetics among breast cancer patients and first-degree relatives of affective individuals. J Genet Counseling 6:111-129, 1997 13. Tessaro I, Borstelmann N, Regan K, et al: Genetic testing for susceptibility to breast cancer: Findings from women's focus groups. J Womens Health 6:317-327, 1997[Medline] 14. Winer E, Borstelmann N, Bluman L, et al: Attitudes and risk perceptions of women with breast cancer considering testing for BRCA1/2. Proc Am Soc Clin Oncol 15:537a, 1997 (abstr 1937)
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Lerman C, Croyle R: Psychological issues in genetic testing for breast cancer susceptibility. Arch Intern Med 154:609-616, 1994 34. Parmigiani G, Berry DA, Aguilar O: Determining carrier probabilities for breast cancer susceptibility genes BRCA1 and BRCA2. Am J Hum Genet 145-158, 1998 35. Hiller EH, Parmigiani G, Berry DA, et al: Validity testing of a computer model for calculating carrier probabilities of BRCA1 and BRCA2 mutations. 1997 Meeting of the American Society of Human Genetics, Baltimore, MD, October 28-November 1, 1997 (abstr) 36. Hilsenbeck SG, Wenger CR, Reynolds LP, et al: Early results of genetic testing for breast cancer susceptibility. Breast Cancer Res Treat 46:38, 1997 (abstr) 37. Iversen ES, Parmigiani G, Berry DA: Validating Bayesian prediction models: A case study in genetic susceptibility to breast cancer, in Case Studies in Bayesian Statistics IV (in press) 38. Agresti A: Categorical Data Analysis. New York, NY, Wiley-Interscience, 1990, pp 365-370 39. Rimer BK, Sugarman J, Winer E, et al: Informed consent for BRCA1 and BRCA2 testing. Breast Dis 10:99-114, 1998 40. Croyle R, Lerman C: Psychological Effects of Screening for Disease Prevention and Detection. New York, NY, Oxford University Press, 1995 41. Rimer BK: Toward an improved behavioral medicine. Ann Behav Med 19:6-10, 1997[Medline] 42. Andrews LB: Commentary: Compromised consent—deficiencies in the consent process for genetic testing. J Am Med Wom Assoc 52:39-44,42, 1997 43. Brzustowicz LM, Allitto BA: Clinical molecular genetic testing. J Am Med Wom Assoc 52:11-15, 1997 Submitted April 27, 1998; accepted November 18, 1998.
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Copyright © 1999 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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ABSTRACT
INTRODUCTION
2 tests or Fisher's exact tests were performed to determine whether there were significant associations between categorical variables of interest. Those variables found to be associated with the outcome of interest at P 
