Ovarian cancer

Since the identification of the BRCA1 (1) and BRCA2 (2) genes, predictive genetic testing for hereditary breast or ovarian cancer (HBOC) became possible in many countries. The availability of predictive testing has allowed the identification of unaffected mutation carriers before they develop breast or ovarian cancer. This technological evolution has the advantage that early detection and preventive strategies can be directed to those who are at increased risk because they are carriers of a BRCA1 or BRCA2 gene mutation and that noncarriers of a mutation can be released from either an intensive medical follow-up or prophylactic surgery. However, regular surveillance and prophylactic surgery have limitations regarding their ability for early detection or prevention of cancer and can have major physical as well as psychological implications. (3,4)

Up to now, only a few published data (5-8) are available regarding adherence to screening recommendations or use of risk-reducing procedures by clinically unaffected women who had a predictive genetic test for HBOC within a clinic-based genetic testing program. Other studies are conducted in the context of a research program or include affected (ie, cancer patients) as well as unaffected women. (9-15) Apart from differences in results due to different recruitment procedures or health care systems, cultural differences may account for differences in utilization of preventive steps, such as prophylactic surgery. (16,17) Because most available studies are US studies, there is a need for more European studies. Furthermore, as available information regarding efficacy of early detection or preventive measures expands, utilization rates will also possibly vary as a function of the period in which studies take place. Lastly, little is known about factors that play a part in the decision making of carriers of a BRCA1 or BRCA2 mutation regarding health-related behavior after predictive testing.

United States and Canadian studies reported utilization rates of prophylactic surgery in carriers varying from 0-28% (9,11-13) for prophylactic mastectomy and 13-58% (9-15) for prophylactic oophorectomy. A recently published European study (8) reported results in the same range, although utilization rates varied from one center to another from 7-42% of carriers who had a prophylactic mastectomy. In 2 other European studies, a high proportion of clinically healthy women who were revealed to be BRCA1 or BRCA2 carriers opted for prophylactic mastectomy (51% (6); 61% of women ages 30-49 years (5)) or for prophylactic oophorectomy (64%). (6)

Reports on utilization of cancer screening by carriers indicate that participation in breast cancer screening is higher than for ovarian cancer screening. Moreover, data on breast and ovarian cancer screening practices vary from 1 study to another. Sometimes there is very high utilization of mammography (87-93% of carriers) (8,2-14) and relatively high utilization of ultrasound of the ovaries (59-73% of carriers), (8,12,13) while others find that up to 30% did not have a mammogram after the test result (7,9,11) or that the majority did not have an ultrasound of the ovaries. (9,11,15) Performance rates of clinical breast examination and breast self-examination vary between 42% and 97%. Because women who have or had cancer often have higher screening rates, (13-15) one must keep in mind that several of these studies included patients as well as asymptomatic women. Comparison of results of different studies is also difficult because the follow-up period can differ, the age of the women included in analyses differs, accessibility to medical care varies, and the outcome measures also differ from one study to another.

This report is part of a broader study evaluating the emotional and behavioral impact of genetic testing in unaffected women who had a predictive test for HBOC on a self-referral basis within a clinic-based genetic testing program. The aim of the present article is threefold. First, we wanted to describe breast or ovarian cancer surveillance practices and acceptance of prophylactic mastectomy or salpingo-oophorectomy during the first year after predictive testing to add to the sparse number of published European data. Second, we wanted to evaluate the impact of the predictive test result on health-related behavior. Because predictive testing offers the opportunity to dismiss noncarriers from regular follow-up, we hypothesized that noncarriers would have less frequent breast cancer screening than carriers after predictive testing. Finally, we wanted to provide more insight into the factors that play a role in the decision making about health-related behavior.

Many theoretical models (18-20) emphasize the role of cognitive variables or illness representations such as perceived risk, perceived seriousness, and perceived control as important in adopting health-related behavior. The relevance of these factors has been demonstrated in individuals at increased risk for breast or ovarian cancer. (21-24) According to self-regulation theory, (19) cognitive as well as emotional factors play a role in the adoption of health-related behavior. Illness perceptions serve as triggers for the development of action plans for managing the threat (eg, preventive measures). Efforts to manage distress can interfere with or enhance action plans to manage the threat.

There is conflicting evidence regarding the role of distress in health-related behavior in women at increased risk. Some find a positive association, (15,22,25,26) whereas others find a negative association (27-29) or no association. (9,14,30) Apart from differences in results due to methodological issues or due to the abovementioned facilitating or interfering effect that efforts to manage distress can have on action plans, these conflicting results may also be the result of the nature of the health behavior examined. (31) It has been suggested that risk-reducing actions, such as preventive surgery, may be facilitated by distress because of their potential for risk reduction and control and, thus, anxiety reduction. Emotional responses are likely to interfere with disease-detection behavior, such as performing breast self-exam (BSE), because this confronts the individual with the threat of detecting the presence of cancer, which will result in increasing anxiety and distress. Therefore, a curvilinear relationship may exist between distress and disease-detection behavior. Extremely low or high levels of distress will interfere with, while moderate levels of distress will stimulate, this type of behavior. (24) The hypothesis of a curvilinear relationship (29-32) is supported by the results of studies in which researchers measured mild cancer concerns or worries and found a positive association with mammography utilization studies. Researchers who measured severe worries or cancer-related distress symptoms found lower rates of mammography. On the basis of these theoretical considerations, we hypothesized that higher perceptions of risk, seriousness, and control are associated with higher utilization of regular cancer surveillance and prophylactic surgery. With regard to the effect of distress, we expected a positive linear relationship between distress and use of prophylactic surgery. We expected a curvilinear relationship between distress and utilization of regular cancer surveillance, with a moderate degree of distress facilitating screening behavior and very low or very high levels inhibiting it.

METHOD

Study Population

In Leuven, Belgium, predictive testing is offered within a clinic-based genetic testing program to unaffected persons from families in which a BRCA1 or BRCA2 mutation had previously been identified in an affected relative. Upon the identification of the familial mutation, the affected index person is asked to inform adult relatives about the hereditary nature of the cancer in their family and the availability of a predictive test. An informational leaflet is provided to facilitate communication of information. (33) Unaffected relatives of at least 18 years can then apply for a predictive test on a self-referral basis.

All test applicants are invited to participate in our longitudinal study evaluating the emotional and behavioral impact of predictive testing. Because of the extensiveness of the test battery with many self-report questionnaires, we excluded women older than 65 years for participation in the study. Between April 1999 and July 2003, 71 women who had a predictive test and agreed to participate in our longitudinal study were eligible to be contacted for the 1-year follow-up assessment. Sixty-eight women (34 carriers and 34 noncarriers) agreed to participate (response rate = 96%).

Procedures

Our counseling and research protocol has been described extensively elsewhere. (34) Predictive testing for HBOC is offered as a clinical service by a multidisciplinary team. All test applicants receive genetic counseling by a clinical geneticist, followed by a psychological counseling session before mutation analysis is started. During the genetic counseling session, individuals receive information about HBOC and its heritability, cancer risks, the predictive test and its implications, the options for prevention and early detection, and the benefits and limitations of these options. The major aims of the pretest psychological counseling session are to provide individual emotional support and decision counseling and to discuss family communication. Following the disclosure of the predictive test result, we systematically offer psychological follow-up (eg, 1 month, 1 year, 5 years) and recommend medical follow-up. If a woman is considering preventive mastectomy, additional counseling is provided before and after surgery.

During the pretest psychological counseling, we inform individuals about the longitudinal study and obtain permission to use interview data and self-report questionnaires for research purposes. We gathered research data with a semi-structured interview that is filled in during the counseling session by the counselor, and we administered self-report questionnaires at the end of each session. Because of the organization of our clinical practice, in most cases these self-report questionnaires were filled out at home and returned by mail. One-year psychological counseling mostly took place in person for carriers, while noncarriers generally received telephone counseling. Consequently, we then conducted the follow-up semistructured interview for carriers in person, while for noncarriers it was conducted by telephone.

Measures

We collected sociodemographic variables and disease-related variables during the pretest interview, including age, education, marital status, number of children, and family history of breast or ovarian cancer.

Regular Surveillance or Prophylactic Surgery

At pretest, we assessed health-related behavior with self-report questionnaires. Participants indicated the frequency of breast self-examination (eg, never, less than once a year, few times a year, monthly, weekly, daily), clinical breast examination (eg, never, less than every 2 years, every 2 years, yearly, every 6 months, more than 2 times a year), mammography (or ultrasound of the breasts), and ultrasound of the ovaries. Participants also indicated whether they had prophylactic risk-reducing surgery.

During the 1-year follow-up session, we assessed health-related behavior in carriers during the semi-structured interview. We asked carriers about their decision making regarding prophylactic mastectomy or salpingo-oophorectomy. For carriers who did not undergo prophylactic mastectomy, we assessed the self-reported frequency of breast self-examination (eg, never, less than once, a few times, monthly, weekly, daily) and clinical breast examination (eg, never, once, every 6 months, more than twice), as well as whether they had a mammogram (or ultrasound of the breasts). We asked carriers who did not have prophylactic salpingo-oophorectomy whether they had ultrasound of the ovaries. We assessed the frequency of breast cancer screening (ie, breast self-examination, clinical breast examination, and mammography) in noncarriers with self-report questionnaires in the same way as in carriers.

Predictors of Health-Related Behavior: Illness Perceptions and Cancer-Specific Distress

In the course of our longitudinal study in 2001, we administered additional pretest questionnaires to gain more insight into the relationship between illness perceptions, cancer-specific distress, and health-related behavior. We implemented these additional questionnaires in 2001. Therefore, all of the following variables (except for perceived control variables regarding breast cancer that were already part of the questionnaires) were only available for 22 carriers and 23 noncarriers.

We measured perceived seriousness of illness with a scale adopted from Champion (35) that consists of 12 statements with which the participants disagreed (= 1) or agreed (= 5) on 5-point Likert-type scales. We calculated the total score by dividing the sum of the individual item scores by the number of items for perceived seriousness of breast cancer ([alpha] = .83) and ovarian cancer ([alpha] = .88), respectively. We measured perceived control with the degree of confidence of participants in (1) early detection of breast cancer by breast self-examination, (2) early detection of breast or ovarian cancer by medical examinations, and (3) the preventability of breast or ovarian cancer by means of prophylactic mastectomy or salpingo-oophorectomy, respectively. This had to be indicated on 7-point Likert-type scales ranging from no confidence (= 1) to full confidence (= 7). We assessed the perceived risk of breast or ovarian cancer with a verbal scale ranging from "I am convinced that I will not develop ... cancer" (= 1) to "I am convinced that I will develop ... cancer" (= 5), with the midpoint of "My risk of developing ... cancer is as high as my risk of not developing ... cancer" (= 3).

We measured cancer-specific distress with the Impact of Event Scale (IES), (36) which consists of 2 subscales: intrusion (the extent to which individuals became overwhelmed by thoughts and feelings about breast and ovarian cancer, respectively) and avoidance (the tendency to avoid these thoughts and feelings).

Decision-Making of Carriers with Regard to Regular Surveillance or Prophylactic Surgery

In the course of our longitudinal study, we slightly modified the posttest semistructured interview. We added open-ended questions regarding the attitudes and motives of carriers toward regular cancer surveillance or prophylactic surgery to the interview and implemented the modified interview in 2001 and conducted in 20 of the 34 carriers who participated in the 1-year follow-up. We asked carriers who did not have prophylactic mastectomy about the advantages and disadvantages of regular surveillance and prophylactic surgery. We asked carriers who chose (temporarily) regular follow-up of the breasts for the decisive motive for this choice. We asked carriers who expressed an intention to have prophylactic surgery in the future for their motives regarding this intended change. We followed the same line of questioning for carriers who did not have prophylactic salpingo-oophorectomy. We asked carriers who had prophylactic surgery why they made this decision and how satisfied they were about it.

Statistical Methods

We compared continuous variables using t tests, or Wilcoxon tests in the case of nonnormality of continuous data. We used Fisher's exact tests for testing proportions and McNemar change tests to determine changes in cancer screening behavior from baseline to follow-up. We divided scores on the IES into tertiles to allow testing of the presence of a curvilinear relationship between distress and use of cancer screening.

For the prediction of use of cancer screening and of prophylactic surgery, we intended to use logistic regression modeling, but it was not possible (see Results section).

The statistical package we used was SAS (Statistical Analysis Software version 8.0).

RESULTS

Characteristics of the Study Population

Table 1 shows the sociodemographic characteristics of participants. Less than 10% of participants were 50 years or older. Participants belonged to 28 families. In 17 families, there was a BRCA1 mutation detected, while in 11 families, there was a BRCA2 mutation found. Twenty-two participants (32%) reported having relatives who had breast cancer at that time or previously and no relatives with ovarian cancer, and 1 participant reported a family history of ovarian cancer only. All others reported relatives with breast cancer as well as relatives with ovarian cancer. Participants received a predictive test result between 1998 and 2002. There were no significant differences between carriers and noncarriers with regard to these characteristics.

Breast Cancer Surveillance or Prophylactic Mastectomy

Choice of Prophylactic Mastectomy

Three carriers definitely decided to have prophylactic mastectomy within the year following the predictive test result (9%). Two of them already had the operation and the third would undergo the operation shortly after the 1-year follow-up assessment. All 3 opted for skin-sparing mastectomy (including the nipple); 2 of them opted for autogenous tissue breast reconstruction and the other for implantation of prostheses. Twenty-four carriers (70%) did not intend to have prophylactic mastectomy, and the remaining 7 (21%) said they would consider it.

Use of Breast Cancer Screening

Table 2 shows data regarding use of breast cancer screening (excluding the 2 carriers who already had prophylactic mastectomy). We considered carriers [greater than or equal to] 30 years who reported the following breast cancer screening measures as adherent: monthly (or more frequent) BSE, semiannual (or more frequent) clinical breast examination (CBE), and yearly mammogram. We considered the others as nonadherent.

Taking into account that regular surveillance is recommended starting at age 30 years, we found that 64% of carriers [greater than or equal to] 30 years were adherent to BSE, 95% to CBE, and 95% to mammography. The pretest adherence rates were 45% for BSE, 14% for CBE, and 63% for mammography. The increase in adherence was significant for CBE (McNemar change test, p < .0001) and mammography (McNemar change test, p < .05). Half of the carriers < 30 years also followed the above guidelines, although they are not recommended for this age group.

To compare carriers with noncarriers, we investigated whether noncarriers [greater than or equal to] 30 years still followed the guidelines recommended to carriers (of course, too strict for noncarriers, but only used to allow a comparison). We found that 40% of the noncarriers performed at least monthly BSE, 30% performed at least semiannual CBE, and 60% had a mammogram. This compares with pretest rates of 45% who performed at least monthly BSE, 15% who performed at least semiannual CBE, and 53% who had annual mammography. We did not find any differences between pre- and posttest rates of use among noncarriers. Compared with noncarriers, carriers were more adherent to the above guidelines for CBE (95% vs 30%, Fisher's exact test, p < .0001) and mammography (95% vs 60%, Fisher's exact test, p < .01) at posttest. Pretest differences were not statistically significant.

A minority of the noncarriers < 30 years followed the above guidelines for carriers (although these guidelines are too strict for them).

Noncarriers are not prescribed to undertake regular surveillance starting at age 30 years. According to national guidelines, women in the general population are offered free mammography screening every 2 years within the age group 50-69 years. However, according to European guidelines, (37) screening can be offered (on an individual basis) to women aged 40-49 years every 12-18 months. Because mammography is not 100% sensitive, monthly BSE and yearly CBE can be an additional tool in the early detection of breast cancer and especially in the stimulation of breast awareness. (38) We inform noncarriers about these guidelines during counseling. Table 3 shows the results about posttest breast cancer screening of noncarriers within different age groups.

Factors Associated With Use of Breast Cancer Screening and of Prophylactic Mastectomy

For the total group of participants of all ages, we tested whether there was a significant association between each of the 3 outcome variables, on the one hand: (1) performing at least monthly BSE or not, (2) performing at least semiannual CBE or not, and (3) having obtained a mammogram or not, and each of the following variables, on the other hand: age, test result (carrier/noncarrier), adherence to guidelines prior to the test (yes/no), and perceived control over breast cancer either by BSE (for the association with BSE) or by medical examinations (for the association with CBE and mammography). The associations between the 3 outcome variables and 3 additional variables could only be tested for a subgroup of participants: cancer-specific distress (IES for breast cancer), perceived seriousness of breast cancer, and perceived risk for breast cancer (only tested for a subgroup because we only measured these 3 variables since 2001; see Method section). Tables 4 and 5 provide an overview of the associations that we tested. It is clear that the outcome measures correspond to the guidelines for carriers older than 29 years and as such they are too strict for the other participants.

There were no significant associations between the series of variables and performing at least monthly BSE.

Women who performed at least semiannual CBE were significantly more likely to be a carrier (Fisher's exact test, p < .0001), were older (t = 2.27, p < .05), and were more likely to have had [greater than or equal to] semiannual CBE prior to predictive testing (Fisher's exact test, p < .01) than women who had less frequent CBE. The relationship between performing at least semiannual CBE and the other variables was not significant. Lack of variability (leading to separation problems) impeded logistic regression analysis: all individuals who had a CBE every 6 months (or more frequently) prior to predictive testing also had at least a semiannual CBE following predictive testing. Also, the combination of test result and age caused separation: all but 1 participant who were carriers and who were older than 29 years had at least semiannual CBE following predictive testing.

Women who had a mammogram after predictive testing were more likely to be a carrier (Fisher's exact test, p < .005), were older, t = 5.94, p < .0001, and were more likely to have had yearly mammograms prior to testing (Fisher's exact test, p < .0005) than women who did not have a mammogram after predictive testing. The relationship with the other variables was not significant. Lack of variability (leading to separation problems) impeded logistic regression analysis: all participants who were carriers and who previously had a yearly mammogram also had a mammogram after predictive testing. Moreover, all but 1 participant who were carriers and who were older than 29 years had a mammogram after predictive testing.

Because of the small number of individuals who had prophylactic mastectomy, we did not conduct any additional analyses.

Decision Making of Carriers Regarding Regular Breast Cancer Screening or Prophylactic Mastectomy

For the subset of carriers who obtained the modified semi-structured interview (n = 20), Table 6 lists all pros and cons of regular breast cancer screening and prophylactic mastectomy reported (as an answer to open-ended questions) by carriers who did not have prophylactic mastectomy or were waiting for the operation (n = 18). All carriers mentioned at least 1 advantage of screening, 10 (56%) reported at least 1 disadvantage of screening, 12 (67%) mentioned at least 1 advantage of surgery, and all carriers revealed at least 1 disadvantage of surgery.

The decisive motives of the 18 carriers to choose for regular breast surveillance were early detection of cancer (n = 8), disadvantages of surgery (n = 8), because of the high risk (n = 3), because risk was reduced (because of age or prophylactic oophorectomy) and, therefore, prophylactic mastectomy is no longer under consideration (n = 3), no relationship or partner does not want prophylactic surgery (n = 2). Five carriers reported more than 1 motive despite the fact that the decisive motive was asked.

Five of these 18 women would consider an operation in the future under the following conditions: at an older age (n = 1), if regular follow-up would lead to recurrent need for biopsies (n = 1), when physical appearance would become less important (n = 1), if regular follow-up is too burdensome or a cancer diagnosis will be made (n = 1), or no specific reason (n = 1).

Two carriers chose prophylactic mastectomy to reduce the cancer risk and prevent the development of cancer. Both were very satisfied with their decision.

Ovarian Cancer Surveillance or Prophylactic Salpingo-oophorectomy

Use of Prophylactic Salpingo-oophorectomy

Prophylactic salpingo-oophorectomy is usually considered in women above age 35 years. Of the 21 carriers who were 35 years or older and who did not have an operation in the past for reasons unrelated to their increased risk (1 woman had salpingo-oophorectomy for other reasons), 5 had prophylactic salpingo-oophorectomy prior to the predictive test request (24%). Twelve of the remaining 16 (75%) had an operation following predictive testing, 1 had concrete plans to have an operation in the near future, 1 would consider it at a later point in time, and 2 did not intend to have prophylactic surgery of the ovaries. Of the carriers younger than 35 years (n = 12), 1 had prophylactic salpingo-oophorectomy at age 34 years, 10 would consider it, and 1 felt unable to express an intention regarding an option that was so remote (woman in her early 20s).

Use of Ovarian Cancer Screening

We considered carriers 30 years or older who did not have prophylactic surgery of the ovaries (n = 5) and who had an ultrasound of the ovaries as adherent. We found that all carriers within this group were adherent. Of the carriers younger than 30 years (n = 10), 3 (30%) had an ultrasound of the ovaries in the year following predictive testing (although this was not recommended by our screening protocol).

Factors Associated With Use of Ovarian Cancer Screening or of Prophylactic Oophorectomy

Because of the small number of carriers opting for ovarian cancer screening and because of high adherence, we did not conduct any additional analyses with regard to adherence to screening for ovarian cancer.

For the prediction of utilization of prophylactic salpingo-oophorectomy following genetic testing (yes/no) associations, we tested with the following variables: age, cancer-specific distress (IES for ovarian cancer), perceived seriousness of ovarian cancer, and perceived risk of ovarian cancer. We did not include the variable "confidence in the preventability of ovarian cancer by means of prophylactic oophorectomy" because of lack of variability and highly skewed distribution (Mdn = 6, range = 4-7). Apart from age, we tested associations within a subgroup of 19 carriers (see Method section).

Compared to women without surgery, women who had prophylactic salpingo-oophorectomy following predictive testing were older, 43.8 (SD = 5.0) vs 28.8 (SD = 8.4), t = 5.68, p < .0001, and had a higher risk perception of ovarian cancer (Wilcoxon test, p < .05). Again, lack of variability (leading to separation problems) impeded logistic regression analysis: carriers with high risk perception all had an operation, while carriers with low risk perception had no operation.

Decision Making of Carriers Regarding Regular Ovarian Cancer Screening or Prophylactic Oophorectomy

For the subset of carriers who obtained the modified semi-structured interview (n = 20), Table 7 lists the pros and cons of regular ovarian cancer screening and prophylactic surgery of the ovaries reported by carriers who did not already have a prophylactic oophorectomy (n = 10). Data for 1 carrier are missing because she felt unable to answer these questions regarding an option that was so remote. All carriers mentioned at least 1 advantage of screening, 7 (78%) reported at least 1 disadvantage of screening, 8 (89%) mentioned at least 1 advantage of surgery, and 8 (89%) revealed at least 1 disadvantage of surgery.

The decisive motives of the 9 carriers to choose regular follow-up were age (n = 5), reproductive decisions (n = 3), no operation when it is not absolutely necessary (n = 2), early detection of cancer (n = 1), and early menopause with operation (n = 1). Three carriers reported more than 1 motive despite the fact that the decisive motive was asked.

Eight of these 9 women receiving unfavorable genetic test results would consider an operation at an older age or when childbearing is complete, and 1 had no intention to have prophylactic surgery.

Nine participants had a prophylactic oophorectomy following predictive testing (1 had surgery before predictive testing for other reasons). The motives of these 9 carriers were reduction of risk or cancer prevention (n = 7), reassurance (n = 2), and doctor's recommendation (n = 1). Eight of these 9 carriers were very satisfied with their decision and 1 was rather dissatisfied, mainly due to menopausal complaints after surgery and lack of information regarding early menopause prior to surgery.

COMMENT

Our findings indicate that predictive testing for HBOC has a significant impact on breast or ovarian cancer surveillance in women receiving an unfavorable predictive test result. Adherence among carriers older than 29 years regarding CBE and mammography was very high in our study (95%). On the other hand, adherence to BSE was not as high (64%). Carriers also had more frequent CBE and were more likely to have a mammogram than noncarriers in the year following the predictive test. This was due to an increase in adherence to recommendations for CBE and mammography in the carrier group and to the absence of a reduction in screening in the noncarrier group. Other studies conducted within a clinic-based genetic testing program also reported relatively high use of CBE and mammography by carriers. (7,8,13) However, the high use of ovarian cancer screening as well as the relatively high proportion of BRCA1 or BRCA2 carriers younger than 30 years who had breast cancer screening are in contrast with other studies. (7,8,15)

The high use of breast or ovarian cancer screening in carriers (at all ages) can be explained in several ways. Studies have shown that women who do not apply for genetic testing are satisfied with the frequent surveillance and that some of the women would not undertake other risk management strategies should they be carriers of a mutation. (39,40) Making decisions about the frequency of screening and about surgery are major reasons to opt for genetic testing. (39,41,42) Also, only a minority of the nontested group in the study of Lodder et al. (40) thought that confirmation of having inherited the mutation would yield a sense of certainty. For tested women, obtaining certainty was an important reason for undergoing testing. (40,43) Therefore, the high use of regular surveillance may be the reflection of the highly motivated nature of individuals actively seeking genetic testing services. For this group, predictive testing may be a way to cope with the increased risk of cancer and a way to gain control, because an unfavorable genetic test result provides "certainty" about the high risk and about the need for regular surveillance. Perceived control over breast or ovarian cancer by means of medical examinations was also high in our group of participants. The lower rate of BSE performance could then be explained by the lower perceived control over breast cancer by means of BSE, but also by the greater behavioral demand of the regimen. However, we cannot exclude that the group of carriers in this study is too optimistic about the controllability of the disease by means of early detection methods and treatment. The findings in our report about the decision making of carriers regarding screening are also in line with the fact that the elicitation of feelings of control and ability to take action with regard to the risk are very important. Only a minority of the carriers mentioned that they considered the fact that the sensitivity of cancer screening is not 100% as a disadvantage. This can reflect the optimistic view as suggested above. However, doing something that is not 100% sensitive may be preferred over doing nothing when confronted with the certainty of being at a high risk and may also be preferred over undergoing something drastic or invasive, such as preventive mastectomy.

Another explanation may be that in Belgium, costs of genetic testing and regular cancer surveillance are covered by public and private insurance, and facilities for genetic testing and cancer screening are highly accessible.

A last explanation is that all individuals received extensive genetic as well as psychological counseling. Physician recommendation (as part of genetic counseling) has been found to be an important factor in adherence to screening. (14,44) An important part of our psychological counseling is scenario development: we asked test participants to explore the possible outcomes and consequences of testing and to anticipate how they would react emotionally and behaviorally. (34) Emotion-focused as well as problem-focused coping received attention. Scenario development facilitates decision making by structuring the decision problem and by stimulating the expression of beliefs, experiences, emotions, motivations, and values. It enhances feelings of personal control by preparing test applicants to cope emotionally and behaviorally with the test result. However, long-term follow-up is needed to evaluate whether the rate of cancer screening will remain high over a longer period of time.

Overall, use of breast cancer screening by noncarriers in this study was also high. The majority of the noncarriers older than 39 years had one (or more) CBE and a mammogram in the year after predictive testing. In Belgium, a national breast cancer screening program is organized for women aged between 50 and 69 years and offers mammography every 2 years without any cost for the women. Additionally, screening takes place outside the nationwide screening project within this age category and also in women younger than 50 years. Furthermore, although still somewhat controversial, breast screening within the 40-49 years age group is acceptable according to European guidelines. (37) Because mammography is not 100% sensitive, monthly BSE and yearly CBE can be an additional tool in the early detection of breast cancer and in the stimulation of breast awareness. (38) Therefore, we can conclude that, except for BSE, noncarriers older than 39 years were highly adherent to guidelines for the general population as they are discussed during genetic counseling. However, noncarriers younger than 40 years also had a CBE after predictive testing, but only a minority had a mammogram. Overall, these results are in line with some other studies and suggest that noncarriers older than 39 years are not falsely relieved about their residual risk of breast cancer but that the younger noncarriers may not have felt reassured that their breast cancer risk is low. (7,9) The overall high usage by noncarriers of some kind of breast screening is not in line with lower usage rates usually reported for women in the general population. (38) Based on our clinical experience, we think this can be explained by a higher breast cancer awareness in this group of women because of their family history of cancer and undergoing genetic testing and counseling and, consequently, a higher awareness of the residual population risk of breast cancer. Because of these aspects, noncarriers differ from women in the general population. Therefore, one can assume that health-related behavior is also different. However, long-term follow-up is needed to evaluate whether this behavior persists or whether adjustment to the new genetic status over time wards off the threat of cancer and consequently leads to a reduction in cancer screening.

Carriers' requests for prophylactic salpingo-oophorectomy were higher than for prophylactic mastectomy, which is in line with other studies. (6,8,11,12) The majority had a prophylactic salpingo-oophorectomy or considered it in the future, whereas only a few carriers had a prophylactic mastectomy and the majority had no intention to have the latter procedure. The invasive nature of prophylactic mastectomy and the availability of early detection methods can explain the lower utilization when compared with prophylactic salpingo-oophorectomy. Although prophylactic salpingo-oophorectomy also has limitations regarding the prevention of cancer, the less reliable screening methods to detect early ovarian tumors and the less disfiguring nature of preventive surgery of the ovaries probably explain the high (intended) use.

Differences in attitudes and use of prophylactic surgery have been explained by cultural differences. (9,17) The period in time during which genetic testing and follow-up had taken place is also important to consider because it was suggested that utilization of prophylactic surgery will increase when more data become available on its efficacy. (9,15) On the other hand, it has been found that prophylactic surgery mostly takes place shortly after disclosure of the test result (6) and, therefore, one would expect that use would not increase with a longer follow-up period. However, within our study population, prophylactic mastectomy did not take place shortly after disclosure of the test result and, therefore, use may indeed increase over a longer follow-up period. Furthermore, not only more data on efficacy, but also increasing acquaintance with the use of this type of intervention through media and the Internet, can lead to less unfavorable attitudes toward prophylactic mastectomy. Apart from the above explanations, it can be hypothesized that the relatively low (intended) utilization of prophylactic mastectomy compared with other European data (5,6,8) may be explained by the fact that, besides reconstruction by implantation of prostheses, autologous tissue reconstruction is performed at our university hospital. Although this reconstruction technique greatly diminishes the risk of long-term complications, women may be more reluctant to undergo preventive mastectomy or need a longer period of time to take this option into consideration because the initial operation is more disfiguring and also more expensive.

Although it was our initial aim to delineate predictors of regular cancer screening, lack of variability in our data impeded the examination of predictors in our relatively small study group. It also explains to some extent why pretest psychological factors (ie, cognitive and emotional) were not found to be associated with posttest utilization of cancer screening and prophylactic surgery. Also, several other studies did not find associations between psychological factors and health-related behavior following genetic testing. (7,9,11,14) It is, however, important to keep in mind that this lack of variability generally is the result of high utilization of screening and prophylactic oophorectomy, which is a positive finding. The above discussion can shed some light on potential causal factors of these high (or low for prophylactic mastectomy) utilization rates.

We tried to provide insight into the decision-making process of carriers regarding regular cancer screening or prophylactic surgery. Carriers were more homogeneous with regard to the formulated advantages of regular screening and prophylactic surgery than with regard to the disadvantages that were more individually different. The most cited advantages of regular screening and prophylactic surgery were early detection of cancer and reduction of cancer risk, respectively. Furthermore, for carriers who have chosen regular screening after predictive testing, arguments against prophylactic mastectomy were also decisive for this choice. Although only a minority of the carriers reported emotional motives, one could assume that the reported (rational) risk-reducing motives incorporated an emotional distress-reducing effect. Early detection of cancer was also reported as an advantage of screening for the ovaries, although efficacy is not good. However, this advantage was reported by the younger carriers, who did not have prophylactic surgery yet but who had the intention to have surgery at a later point in time (at an older age, when childbearing is complete). For these young women, regular surveillance of the ovaries is the only means for control at that point and is an adaptive reaction considering their rather low risk of ovarian cancer at their age. Again, doing something that is not 100% sensitive is preferred over doing nothing while waiting for surgery to take place at an older age. The most cited disadvantages of prophylactic mastectomy were a negative impact on the external physical appearance and body image, whereas internal hormonal changes were considered in the case of prophylactic oophorectomy.

There are limitations to this study. The study sample was small and, therefore, there may be a lack of statistical power to detect certain effects. The small sample size and the fact that several women were members of the same family may be an impediment to the generalizability of the results. Moreover, women actively seeking predictive testing are probably a highly motivated group and may not be representative of all high-risk women from families in which a BRCA1 or BRCA2 mutation has been detected. So far, little is known about health-related behavior of women from families with a known BRCA1 or BRCA2 mutation who do not come forward for predictive testing. Research in this group of women is very important to see whether women not opting for predictive testing are also less inclined to be adherent to screening recommendations or to utilize preventive surgery. Women who do not come forward for predictive testing may be less well informed about recommendations regarding health-related behavior or may not even be aware of the possibility of predictive testing due to a lack of communication in the family. (33,45) Another limitation of our study, as for other studies, is that the data on health-related behavior were based on self-reports, which could lead to an overestimation of actual utilization. However, previous research suggested that mammography self-reports are valid. (46)

Our study evaluated health-related behavior within the year after predictive testing for hereditary breast and ovarian cancer. Overall, our results are encouraging with regard to carriers' high rates of utilization of cancer screening following positive predictive testing. However, for many women, it may become difficult to continue regular cancer screening for a very long time, and women may be confronted with the decision whether to undergo prophylactic surgery at some point in their lives. Therefore, a longer follow-up period is mandatory to evaluate the impact of predictive testing and counseling on health-related behavior over a longer period of time.

ACKNOWLEDGMENTS

We thank all the women who participated in the study. We explicitly express our gratitude to the editor for the very helpful editorial comments and suggestions.

NOTES

For comment or further information, please address correspondence to Prof. Gerry Evers-Kiebooms, PhD, Psychosocial Genetics Unit, Center for Human Genetics, Herestraat 49, (B) 3000 Leuven, Belgium (e-mail: gerry.kiebooms@uz.kuleuven.ac.be).

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Erna Claes, PhD; Gerry Evers-Kiebooms, PhD; Marleen Decruyenaere, PhD; Lieve Denayer, PhD; Andrea Boogaerts; Kristien Philippe; Eric Legius, MD, PhD

Drs Claes, Evers-Kiebooms, Decruyenaere, and Denayer, Ms Boogaerts, and Ms Philippe are with the Psychosocial Genetics Unit, and Dr Legius is with the Clinical Genetics Unit. All are with the Center for Human Genetics, University of Leuven, Belgium.

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