Psychological Responses to BRCA1 Mutation Testing ...

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addressed to Robert T. Croyle, Department of Psychol- ogy, University of Utah, ... robert[email protected]. .... pate in a prospective study that included the.
Health Psychology 1997,%!. 16, No. 1,63-72

Copyright 1997 by the American Psychological Association, Inc. 0278-6133/9743.00

Psychological Responses to BRCA1 Mutation Testing: Preliminary Findings Robert T. Croyle, Ken R. Smith, Jeffrey R. Botkin, Bonnie Baty, and Jean Nash University of Utah

The short-term psychological responses of 60 adult women tested for a BRCA1 gene mutation associated with a high risk of breast and ovarian cancer were investigated. Participants were members of a large kindred enrolled in an ongoing prospective study of the psychosocial impact of genetic testing. Initial results from participants who completed both the pretest baseline and the 1-2 week posttest follow-up interviews are reported. Gene mutation carriers manifested significantly higher levels of test-related psychological distress, as measured by the Impact of Event Scale, when compared with noncarriers. The highest levels of test-related distress were observed among mutation carriers with no history of cancer or cancer-related surgery. Although general distress (state anxiety) declined after testing, carriers were more distressed than noncarriers at follow-up. Key words: cancer, genetic testing, BRCA1, screening

In the fall of 1994, a group of researchers identified a gene that had been the target of an intensive international investigation. Mutations in this gene, BRCA1, have been linked to a greatly increased risk of breast and ovarian

cancer among women who inherit the mutation (Miki ct'al., 1994). In the families studied to date, the risk of breast cancer in female carriers by age 70 is 85%; the risk of ovarian cancer by age 70 is 63%. The risk of carriers contracting either cancer by age 70 is 95% (Easton, Ford, & Bishop, 1995). Although most breast cancers in the gen-

Robert T. Croyle, Department of Psychology, University of Utah; Ken R. Smith, Department of Family and Consumer Studies, University of Utah; Jeffrey R. Botkin and Bonnie Baty, Department of Pediatrics, University of Utah; Jean Nash, Department of Human Genetics, University of Utah. This article presents preliminary findings of an ongoing research project that is supported by grants from the National Cancer Institute, CA 63681, and the National Center for Research Resources, MO1RR00064. We thank David Goldgar, Jamie McDonald, Corinne Halls, John Ward, Bonnie Flick, Caryn Lerman, Debra Dutson, Vickie Venne, Elaine Lyon, Linda Steele, Lisa Coy, Ken Ward, and James McGreevy for their valuable help in conducting this project. Jennifer Achilles and Mary Lou Gomy provided valuable comments on a draft of the article. Correspondence concerning this article should be addressed to Robert T. Croyle, Department of Psychology, University of Utah, Salt Lake City, Utah 84112. Electronic mail may be sent via Internet to [email protected].

eral population cannot be attributed to an inherited predisposition, BRCA1 mutations appear to account for approximately half of familial breast cancer cases and 5% of all breast cancer cases (Szabo & King, 1995). Although research-based testing for BRCA1 mutations is now underway at several sites in North America and Europe, very little is known about the psychological

impact of this new

technology. Early reports relied on a very small number of participants (Dudok de Wit et al., 1994;

Watson et al.,

1995) or on anecdotal

evidence collected in interviews (Lynch et al., 1993). Given the high level of interest in BRCA1 mutation testing among both high-risk and average-risk women (Croyle, Dutson, Tran, & Sun, 1995; Lerman, Seay, Balshem, & Audrain, 1995; Struewing, Lerman, Kase, Giambarresi, & Tucker, 1995), it is important to determine the nature and

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extent of the psychological impact of this new technology on participants. In anticipation of the gene's discovery, we obtained funding from the National Cancer Institute in 1994 to conduct an extensive evaluation of the impact of BRCA1 testing in one large, Utah-based kindred. Our study focuses on the psychosocial impact of genetic testing on both men and women, but also includes an exploration of potential changes in employment, insurance coverage, and health care utilization. This article presents our first examination of data collected to date from individuals who have received their genetic test results. In this preliminary analysis, we compare levels of psychological distress in women who tested positive for a BRCA1 mutation with distress in women who tested negative. Because standard clinical protocols for cancerrelated genetic testing have yet to be developed, it is important that physicians and genetic counselors are informed by empirical evidence concerning the psychological impact of test results. The first question we addressed, therefore, is a simple one: Do individuals informed that they carry a BRCA1 mutation experience significantly greater distress following testing than those informed that they do not carry a BRCA1 mutation? Psychological research concerning genetic testing has grown from a small, obscure set of studies to a rapidly growing body of work carried out by an increasing number of investigators. Much of the research has been stimulated by recent discoveries in molecular genetics and the ethical and social issues raised by predictive testing in healthy individuals (Collins, 1996; Lerman, Rimer, & Engstrom, 1991; Rothstein, 1990). A recent review of the literature (Croyle & Lerman, 1995) found that much of the earlier work involved small numbers of participants, uncontrolled research designs, and highly self-selected samples of participants. Recently, however, data from several controlled prospective studies of individuals undergoing testing for adult-onset disorders such as Huntington's disease have been published (e.g., Tibben et al., 1994; Wiggins et al., 1992). These data suggest that participants manifest a wide variety of psychological responses to predictive genetic testing, with a tendency for both carriers and noncarriers to show decreased distress six months after the provision of test results.

One factor that might moderate responses to genetic test results is an individual's personal medical history. In clinical settings, some individuals are referred for genetic counseling after a diagnosis of cancer, whereas others are referred because they are a blood relative of a cancer patient. These two groups of individuals might differ psychologically in important ways. Individuals in a disease-prone family who have experienced the disease might assume that their own case was determined by inherited factors. In the case of breast and ovarian cancer, this may or may not be an accurate assumption. Sporadic cases of cancer of unknown origin occur even in families with inherited cancer syndromes. Nevertheless, these individuals might be psychologically prepared for a genetic test result that shows they carry a predisposing mutation. Similarly, unaffected individuals who have undergone prophylactic surgery might also be less distressed by a positive mutation test because of a longstanding expectation that they carry the mutation. This is consistent with both theory and research concerning emotion, which suggest that negative events produce greater distress when they are unexpected (Lazarus & Folkman, 1984; Ortony, Clore, & Collins, 1988). In this study, we conducted a preliminary examination of predictors of distress following BRCA1 mutation testing. The primary independent variables were carrier status as determined by DNA testing and cancer or cancer-related surgery history. Two forms of psychological distress, one general and one specific, were measured. The State Anxiety scale of the StateTrait Anxiety Inventory (STAI; Spielberger, 1983) was used as a measure of general distress because of its well-established validity and its use in other studies of genetic testing (Croyle & Lerman, 1995). A review of previous research concerning cancer screening suggested the Impact of Event Scale (IBS; Horowitz, Wilner, & Alvarez, 1979) may be a more sensitive measure of the specific distress induced by risk notification than measures of general distress. The IBS also was designed to measure stress related to a specific event, and includes an explicit assessment of the cognitive manifestations of worry and anxiety (e.g., thought intrusion). We expected that psychological distress following genetic testing would vary as a function of

SPECIAL ISSUE: RESPONSES TO BRCA1 TESTING test result. Individuals who were informed that they are carriers were expected to report greater distress than noncarriers. In addition, we predicted that the impact of test results would be moderated by a woman's medical history. Women with no personal history of cancer or prophylactic surgery were expected to experience greater distress when informed of their carrier status than women with such a history. Age was considered as a confounder because older women are more likely than younger women to have a personal history of cancer or cancer-related surgery. Older women might also be less likely than younger women to report psychological distress within the context of a telephone interview. Level of education also was considered as a confounder because of its well-established association with preventive health behavior (e.g., Gottlieb & Green, 1984).

Method Participants The data reported here are from 60 women who enrolled in the large prospective study described above of the psychosocial and behavioral impact of BRCA1 mutation testing. The age of the participants at the time of enrollment ranged from 19 to 83 years (M = 47.0). Most of the participants were married (n = 51, 85.0%), 2 were divorced, and 7 were single. Over one third (n = 22, 36.7%) were college graduates. All but 2 of the women reported their religious affiliation as Mormon (Church of Jesus Christ of Latter-Day Saints). All of the study participants are members of a large Utah-based kindred of Northern European descent (Goldgar et al., 1994), which has been studied previously because of the high incidence of breast and ovarian cancer among its family members. Research conducted by a team of investigators based at the University of Utah established that most of the breast and ovarian cancers in the extended family can be attributed to a specific inherited mutation in the BRCA1 gene on chromosome 17 (Miki et al., 1994). Once the gene and the family-specific mutation were identified, clinical testing for kindred members was offered through this project. Among the first 213 women who had re-

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sponded to contact letters as of January 12,1996 (which included the potential participant sample for this report), 179 (84.0%) expressed interest in participation, 12 (5.6%) requested more information, 18 (8.5%) requested no further contact regarding the study, 1 was elderly and ineligible because of poor health, and 3 declined genetic counseling and testing but agreed to enroll in an interview-only study track (additional details concerning recruitment, enrollment, and drop out at the various stages of the protocol will be reported in another article).

Procedure The overall study protocol is described in detail elsewhere (Botkin et al., 1996). To summarize, kindred members aged 18 years and over were first contacted by letter and asked to participate in a prospective study that included the opportunity to undergo free genetic counseling and testing. Enclosed with the letter was a response form and a stamped, self-addressed envelope. Individuals could either express interest in participation, request more information about the study, or request no further contact. The initial wave of letters was sent to members of the oldest generation from branches of the kindred who had previously participated in an earlier genetic linkage study. Letters were then sent to members of the next generation of the branch, and then to family members who had not previously participated in research but whom a family member had given us permission to contact. To protect the privacy of parents' genetic information, children of people who declined to participate were not contacted unless the parent provided written consent to do so. The second contact with participants who expressed interest was by telephone. A brief description of the study was provided, and any questions were answered. Consent forms were mailed to participants who were still interested or requested more information (97.4%), who then signed and returned the forms. The individuals were then contacted by telephone to schedule the baseline interview. Participants who completed the baseline interview were scheduled to meet with a genetic counselor and a marriage and family counselor. Meetings with these two clinicians were con-

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ducted separately but on the same day. Generally, about 2 hr were spent in pretest counseling and psychosocial assessment. The initial genetic counseling session included a cancer family history, a targeted medical and cancer screening history, and information concerning the following: cancer and cancer predisposition, the BRCA1 gene and its mode of inheritance, cancer risks associated with mutations, the method used for DNA analysis, and an overview of prevention and surveillance options available for mutation carriers and the general population. The risks, benefits, and limitations of testing were reviewed, including psychological risks and the risk to the participant's employment and insurance status. Participants then had the option of having blood drawn for the DNA test, which was a direct polymerase chain reaction test for a specific BRCA1 mutation performed by the University of Utah's DNA Diagnostic Laboratory (Kenneth Ward, Director). Results were provided in person at a second session attended by both the genetic counselor and either a psychiatrist, a marriage and family counselor, or a psychologist. Participants were encouraged to bring to this results session a support person who was not a blood relative. Results sessions with noncarriers generally lasted approximately 20-30 min, and results sessions with mutation carriers lasted approximately 30-60 min. In addition to the disclosure of test results, participants were provided with medical recommendations and strategies to cope with personal risk and altered risks to family members that were due to the participant's results, referral to consultants and community resources, and a review of material from the first genetic counseling session, when appropriate. Psychological issues were addressed throughout the sessions as they arose. Letters reviewing the information were sent to the participant after each counseling session. The first follow-up telephone interview was conducted 1-2 weeks after the test results session. The protocol also includes scheduled interviews at approximately 4 months, 1 year, and 2 years after test results. As of January 12, 1996, only 1 participant who received test results had refused to complete the 1-2 week follow-up interview. Most of the women in the larger study

referred to above are still enrolled in the study protocol at various stages, but had not yet completed genetic counseling, testing, and initial follow-up interviews as of January 12,1996.

Measures An extensive battery of measures was administered in both the baseline and follow-up interviews. Demographic (age and education), perceived risk, and health history data were included in the baseline interview. In addition, a packet of questionnaires was mailed to the participant immediately before the follow-up interview. In this article, we focus on the results from two measures of psychological distress administered in the telephone interviews. General psychological distress. The 20-item State Anxiety scale of the STAI Form X (Spielberger, Gorsuch, & Lushene, 1970; Spielberger, 1983) was administered both at baseline and at the 1-2 week follow-up. The STAI is a wellestablished and widely used measure of current, general distress. Each item is rated on a 4-point scale, yielding a total possible State Anxiety score range from 20 to 80. Test-related distress. The IBS (Horowitz et al., 1979; Zilberg, Weiss, & Horowitz, 1982) was administered in the follow-up interview. The IBS is a 15-item scale that measures event-related distress. Because the measure was used in this study to assess responses to genetic test results, it was not administered at baseline. The IBS yields a total score and subscores for Intrusion and Avoidance. Interviewers read the following introduction to the scale items: "I am going to read a list of comments made by people after they have received their genetic test results. When you hear each comment, think about your thoughts and feelings toward the test result in terms of you personally as well as your family. Please tell me how often each of the comments was true for you since you have received your test results." Both measures showed high internal consistency. For the data sample described here, the Cronbach's alpha for the STAI measure was .94 at baseline and .95 at follow-up. For the IBS at follow-up, it was .88.

SPECIAL ISSUE: RESPONSES TO BRCA1 TESTING

Cancer or cancer-related surgical operation history. Medical history was considered a moderator variable. Data were collected by means of self-report in the baseline interview. Participants were asked if they had ever been told by a physician that they had any type of cancer. In addition, they were also asked if they had their breasts or ovaries removed. Participants who answered yes to either question were considered as having a cancer or cancer-related surgery history. For some of the operations reported by women with no cancer history, it was difficult to determine whether the procedure was purely prophylactic or was prompted by cancer signs and symptoms. Some oophorectomies might have been conducted as part of a hysterectomy. Results BRCA1 Mutation Test Results Of the 60 women tested, 25 were determined to be mutation carriers and 35 to be noncarriers. Demographic characteristics and cancer or cancerrelated surgery history of the two groups are described in Table 1. As indicated in Table 1, most (71%) of the women with a history of breast or ovarian cancer tested positive for the BRCA1 Table 1 Characteristics ofBRCAl Mutation Carriers and Noncarriers Mutation test result

Variable Age in years (M) % with college degree Cancer or cancer-related surgery history (self-reported) Breast cancer Ovarian cancer Uterine cancer Skin cancer Colon cancer Oophorectomy Total with history Total without history

Noncarrier (n = 35)

Canier (« = 25)

49.6

43.3

40

40

2 0 0 1 1 14" 16 19

3 2 1 0 0 6 12 13

"Includes 1 participant with a history of colon cancer and 1 participant with a history of breast cancer,, list listed above.

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mutation. In addition, some of the noncarriers had a history of other cancers. Psychological Distress We first examined baseline levels of general psychological distress in our sample. For the 60 women in our sample, the mean State Anxiety scale score was 34.87 (SD = 11.91). This average level of anxiety is nearly identical to that observed in a normative sample of women (Spielberger, 1983), although it should be noted that scores ranged widely, from 20 to 67. State Anxiety scale scores at baseline were significantly correlated with State Anxiety scale scores (r = .81, p < .001) and IBS total scores (r = .46, p < .001) at follow-up. Next, we examined the relationship between demographic control variables and the distress measures. Age was not associated with State Anxiety scale scores at baseline (r= — .06, ns) or follow-up (r = .07, ns), but was correlated with IBS total scores at follow-up (r = -.27,p < .05). The participant's level of education was not associated with either State Anxiety scale scores or IBS scores, and was therefore excluded from the regression analyses. Test-related distress. A hierarchical regression analysis was conducted to test the study hypotheses. Age and general distress (State Anxiety scale scores) at baseline were entered in the first block. Cancer or cancer-related surgery history was entered in the second block along with carrier status (mutation test result). Finally, a multiplicative term reflecting the interaction of cancer history and carrier status was entered in the final block. Results of the regression analysis are displayed in Table 2. As Table 2 indicates, State Anxiety scale baseline scores significantly predicted IBS scores at follow-up. Participants who were more anxious at baseline manifested more test-related distress in the posttest interview. In addition, there was a significant effect of lest results on test-related distress, with mutation carriers experiencing greater distress than noncaniers. Finally, the interaction of carrier status and cancer or cancer-related surgery history was marginally significant. Adjusted mean IBS scores are displayed in Figure 1. Mean adjusted IBS scores for

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CROYLE, SMITH, BOTKIN, BATY, AND NASH

Table 2 Hierarchical Multiple Regression Predicting Impact of Event Scores at 1-2 Week Follow-Up Step and variable

Afl2

Step 1 Age STAI-State Anxiety scale scores at baseline Step 2 Cancer or cancer-related surgery history Carrier status Step 3 Carrier Status X Cancer or Cancer-Related Surgery History

.27***

Final p -.12

.45 * * * .10** .05 .51*** .04* -.33*

1

Note. K model = .41, F(5,54) = 7.56,p < .001. STAI = State-Trait Anxiety Inventory. *p = .056. **p < .05. ***p < .001.

noncarriers at follow-up were 9.16 (SD = 6.39) for those with no cancer or cancer-related surgery history and 9.56 (SD = 5.90) for those with a history. For carriers, the means were 22.38 (SD = 5.02) for those with no cancer or cancerrelated surgery history and 11.58 (SD = 5.48) for those with a history. In order to better understand the nature of the interaction, the interaction was decomposed by examining the effects of each of the four combinations of carrier status and history through the use of dummy variables. Separate dummy variables were introduced for the categories carrier with no history, carrier with history, and noncamer with

history. The reference group for comparison included noncarriers with no cancer or cancerrelated surgery history. The analysis showed mat the interaction was largely accounted for by the difference between the reference group and the carrier with no history group O = .43, p < .001). The greatest distress was reported by women who were BRCA1 mutation carriers and had no personal history of cancer or cancer-related surgery.1 Given prior research showing different relationships between the IBS subscales and other study variables (e.g., Epping-Jordan, Compas, & Howell, 1994; Lerman et al.t 1993), we repeated the regressions for each of the IBS subscales, avoidance and intrusion. To summarize, the pattern of findings was replicated across the two measures, but with slightly stronger main and interaction effects on intrusion. Using intrusion as the dependent variable, both the main effect of carrier status (final (3 = .54, p < .001) and the interaction between cancer or cancer-related surgery history and test results (final £ = .40, p = .023) were statistically significant. For avoidance, the main effect of carrier status (final (3 = .49, p < .01) was statistically significant, but the interaction term was not (final 3 = .30, p = .092). The correlation between the avoidance and intrusion subscales was .68 (N = 60, p < .001). General distress. A similar analysis was conducted to test predictors of general distress at follow-up as measured by the State Anxiety scale. Because of missing data, only 58 of the 60 participants were included in this analysis. Results of the analysis are displayed in Table 3. In the hierarchical regression, the first block of variables (age and State Anxiety scale score at baseline) significantly predicted posttest State Anxiety scale scores, F(2, 55) = 59.38, p< .001. Baseline anxiety scores predicted scores that were approximately 20% lower at follow-up 1

Carriers

Non-Carriers

Figure 1. Adjusted mean Impact of Event Scale (BBS) scores at 1-2 week follow-up. Ca/Surg Hist = cancer or cancer-related surgery history.

Because the cancer or cancer-related surgery group included women with no history of cancer, we also examined the data separating out those women who had breasts or ovaries removed but who reported no history of cancer. The pattern of means was the same, and they suggest that women who had surgical operations but were noncarriers (n = 4, M = 6.5, SD = 4.85) did not experience greater distress after testing relative to other noncarriers. Given the small number of participants in this group, however, this finding should be viewed with caution.

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SPECIAL ISSUE: RESPONSES TO BRCA1 TESTING

(final unstandardized p = .78). This reflects an overall decline in general distress between the baseline interview and the 1-2 week follow-up interview. The second block of variables entered (cancer or cancer-related surgery history and mutation test result) was statistically significant (p < .05). Of the two variables, only mutation status was significant, reflecting the fact that carriers reported more general distress than noncarriers. The interaction of cancer or cancer-related surgery history and mutation status was hot significant. Mean adjusted State Anxiety scale scores for noncarriers at follow-up were 27.39 (SD = 8.98) for those with no cancer or cancerrelated surgery history and 33.75 (SD = 10.71) for those with a history. For carriers, the means were 33.61 (SD — 7.12) for those with no cancer or cancer-related surgery history and 33.82 (SD - 10.08) for those with a history. Unadjusted State Anxiety scale scores for carriers and noncarriers at baseline and follow-up are displayed in Figure 2. Discussion These data show that women experience significantly different levels of psychological distress following BRCA1 mutation testing as a function of their test result. After controlling for age and baseline level of general distress, mutation camTable 3 Hierarchical Multiple Regression Predicting General Distress at 1-2 Week Follow-Up Step and variable

A/P

Step 1 Age STAI-State Anxiety scale score at baseline Step 2 Cancer or cancer-related surgery history Carrier status Step 3 Carrier Status X Cancer or Cancer-Related Surgery History

.68***

2

Final 3

.11 .82*** .04** .15 .25** .01

-.13

Note. S model = .73, F(5,52) = 27.61,p < .001. STAI = State-Trait Anxiety Inventory. **p < .05. ***p < .001.

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Baseline

Follow-up

Figure 2. Mean general distress scores at baseline and at 1-2 week follow-up. STAI score = scone from the State Anxiety scale. STAI = State-Trait Anxiety Inventory.

ers manifested more symptoms of test-related distress (as measured by the IBS) and general distress (as measured by the State Anxiety scale of the STAI) than did noncarriers. Across all participants, there was a tendency for general distress to decline approximately 20% between the pretest baseline assessment and the 1-2 week posttest follow-up interview. The latter finding suggests that some of the anxiety experienced by participants enrolled in the study protocol was alleviated by learning their carrier status. Although differences between carriers and noncarriers in test-related distress following testing were expected, it should be emphasized that these differences occurred despite the provision of thorough pretest and posttest counseling. All participants received face-to-face genetic and psychological counseling before and at the time of receiving their test results. Therefore, the levels of distress observed here might underestimate the distress experienced by individuals who undergo BRCA1 mutation testing in clinical settings that do not include similar informed consent processes and counseling services. In addition to the overall effect of test results, we found suggestive evidence of a moderator of this effect. Women who had never experienced cancer or cancer-related surgery or both, but were found to carry the mutation, showed the greatest distress on the IES following testing. These distress scores (M — 22.38) were similar to those

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reported by Epping-Jordan et al. (1994), who interviewed cancer patients an average of 10 weeks after their diagnosis. The mean IBS total score of their sample was 22.92. The relatively high distress in carriers with no cancer or cancer-related surgery history suggests that the experience of cancer or prophylactic surgery can lead to an attenuation of distress than might otherwise occur when a women is informed that she has a cancer predisposing gene mutation. We found that women who had experienced cancer or cancer-related surgical operations perceived a greater likelihood that they were mutation carriers. Consequently, they might have been less surprised about their result. Given their medical history, it is also possible that these women experienced greater cancer-related distress in the past, placing the genetic test within a context that reduced its psychological impact. Our sample size limited our ability to test more comprehensive models of the role of experience and expectations in adjustment to genetic testing. As more women are recruited into our ongoing study, we plan to examine in greater depth these and other factors that might explain the differences between women with and without a cancer or cancer-related surgery history. Our study included measures of both general distress (the State Anxiety scale) and test-specific distress (the IBS). It is important to note that the results of our study might have been interpreted differently had only one of the two measures been included. The measure of general distress yielded mean scores that did not reach clinically significant levels either before or after genetic testing. In addition, average State Anxiety scale scores declined overall from pretest to posttest, especially among noncarriers (see also Lerman et al., 1996). The IBS scale identified one subgroup of participants with a relatively high level of distress after testing and was more sensitive to the interactive effect of cancer or cancer-related surgery history and test result. Investigators interested in studying the psychological impact of genetic testing should consider including both general and specific (especially the intrusion subscale of the IBS) measures of distress in their research protocols. The importance of the distinction between the two types of measures is illustrated in research work showing that general psychological distress is not predictive of the

progression of cancer, whereas avoidance, as measured by the IBS, is (Epping-Jordan et al., 1994; Tross et al., 1996). The characteristics of our participants should be considered when considering the generalizability of these findings. All of the participants in this study are members of a predominantly Mormon kindred of Northern European descent (see Botkin et al., 1996, for further discussion of this issue). Many of these individuals had previously participated in genetics research by providing blood samples and family history information. Because of this, the level of health knowledge and cancer risk awareness may be higher in our sample than in the general population. Adverse psychological effects of genetic testing might be more likely among individuals with less health knowledge and risk awareness. In conclusion, the findings reported here demonstrate that genetic test results can have a short-term impact on psychological functioning even when in-person genetic counseling is provided. Given the preliminary nature of these data and the small sample size, our primary goal was to provide evidence regarding the psychological impact of testing that might inform others who are developing research-based genetic testing protocols. Our findings suggest that the medical experiences of women prior to testing and the expectations they have regarding their genetic status are factors that warrant more thorough investigation. Because the vast majority of women in population-based screening programs would not have had cancer or cancer-related operations, our finding that distress is highest among carriers with these characteristics has significant public health implications. In addition, more data are needed concerning the impact of the levels of distress observed here on adherence to appropriate cancer screening recommendations (e.g., Lerman et al., 1993). As the debates regarding cancer genetic testing continue, it is critical that biomedical scientists and policy makers be informed by empirical evidence regarding the impact of testing on the attitudes, behavior, and psychological functioning of participants. Only through systematic research can we hope to address ethically and comprehensively the needs of patients at risk for breast and ovarian cancer.

SPECIAL ISSUE: RESPONSES TO BRCA1 TESTING

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