Introduction
Interest in and Uptake of Genetic Testing
What People Bring to Genetic Testing: Impact of Risk Perception, Health Beliefs, and Personality Characteristics
Genetic Counseling for Hereditary Predisposition to Breast Cancer
Emotional Outcomes of Individuals
Family Effects
        Family communication about genetic testing and hereditary risk
        Family functioning
        Partners of high-risk women
        At-risk males
        Children
        Reproductive issues
Cultural/Community Effects
Ethical Concerns
Psychosocial Aspects of Cancer Risk Management for Hereditary Breast and Ovarian Cancer
        Decision aids for persons considering risk management options for hereditary breast and ovarian cancer
        Uptake of cancer risk management options
        Cancer screening and risk-reducing behaviors
Psychosocial Outcome Studies
        Risk-reducing mastectomy
        Risk-reducing salpingo-oophorectomy
Interventions: Psychological
Behavioral Outcomes

Introduction

Psychosocial research in the context of cancer genetic testing helps to define psychological outcomes, interpersonal and familial effects, and cultural and community responses. It also identifies behavioral factors that encourage or impede surveillance and other health behaviors. It can enhance decision-making about risk-reduction interventions, evaluate psychosocial interventions to reduce distress and/or other negative sequelae related to risk notification and genetic testing, provide data to help resolve ethical concerns, and predict the interest in testing of various groups.

Research in these areas is limited by few randomized controlled trials, and many reports are based on uncontrolled studies of selected high-risk populations. Research is likely to expand considerably with access to larger populations of at-risk individuals.

There have been a number of descriptions of cancer genetics programs that provide genetic susceptibility testing.[1-9] The development of such programs was encouraged by federal funding of multidisciplinary research programs that offered intensive genetic counseling for hereditary cancer syndromes, psychological assessment and back-up, and physician involvement.[10]

Decisions about whether to pursue breast cancer genetic testing involve complex biologic, behavioral and social elements.[11] There are vast differences in interest in and actual uptake rates of testing reported in the literature. In a systematic review of 40 peer-reviewed primary clinical studies published between 1990 and May 2002,[12] it was reported that sampling frame and other methodological variables contributed to the wide variability. On average, interest in genetic testing was 66% (range 20%-96%), while actual uptake of genetic testing was 59% (range 25%-96%) (odds ratio [OR] 1.27; 95% confidence interval [CI], 1.16–1.39). In multivariate analysis, personal and family history of cancer, study recruitment and setting were all associated with testing uptake.

Furthermore, accrual statistics in different populations are difficult to compare because there are many points in the genetic risk assessment process at which a family member can decline, and no standard method of reporting these rates has been developed.[13] Factors that may influence uptake of testing include:

• Cost of genetic testing.
• How informative testing would be (e.g., presence of a known mutation in the family or ethnic group vs. lack of an identified mutation).
• Extent to which genetic test results are likely to influence clinical decision-making.[14]

Motivations for testing include the belief that testing positive would increase one’s motivation to get regular clinical breast examinations, to do breast self-exams, and to get recommended mammograms.[15] Women known to be at increased risk do not necessarily adhere to screening recommendations at higher rates than women at population risk, nor do they necessarily pursue or complete genetic testing, though the data on this subject are contradictory.[16-18] An additional motivation for testing is to receive information that would benefit other family members.[19] Another motivator for testing may be recommendation by a physician. In a retrospective study of 335 women considering genetic testing, 77% reported that they wanted the opinion of the genetics physician about whether they should be tested, and 49% wanted the opinion of their primary care provider.[20]

In one study of women who pursued BRCA1 and BRCA2 mutation testing and received uninformative test results, 45% (17/40) were interested in undergoing additional testing for five large rearrangements (deletions and insertions) in the BRCA1 gene. There were no significant differences in BRCAPRO scores, age at time of genetic testing, number of children, or number of siblings between individuals who chose to pursue additional testing and those who declined. Women who chose to undergo additional testing were significantly less likely to have a diagnosis of breast or ovarian cancer at the time of initial testing.[21]

Limited data are available about the characteristics of at-risk individuals who decline to be or have never been tested. It is difficult to access samples of test decliners since they are people who also may be reluctant to participate in research studies. Studies of testing are difficult to compare because people may decline at different points and with different amounts of pretest education and counseling. One study found that 43% of affected and unaffected individuals from hereditary breast/ovarian cancer families completing a baseline interview regarding testing declined. Most individuals declining testing chose not to participate in educational sessions. Decliners were more likely to be male and unmarried and had fewer relatives affected with breast cancer. Those decliners who had high levels of cancer-related stress had higher levels of depression. Decliners lost to follow-up were significantly more likely to be affected with cancer.[22] Another study looked at a small number (n = 13) of women decliners who carry a 25% to 50% probability of harboring a BRCA mutation and found that these nontested women were more likely to be childless and have a higher educational level. This study showed that most women had decided not to undergo the test after serious deliberation about the risks and benefits. Satisfaction with frequent surveillance was given as one reason for nontesting in most of these women.[23] Other reasons for declining included having no children and becoming acquainted with breast/ovarian cancer in the family relatively early in their lives.[22,23] A third study evaluated characteristics of 34 individuals who declined BRCA1/2 testing in a large multicenter study in the United Kingdom. Decliners were younger compared with a national sample of test acceptors, and female decliners had lower mean scores on a measure of cancer worry. Although 78% of test decliners/deferrers felt that their health was at risk, they reported that learning about their BRCA1/2 mutation status would cause them to worry about the following:

• Their children's health (76%).
• Their life insurance (60%).
• Their own health (56%).
• Loss of their job (5%).
• Receiving less screening if they did not carry a BRCA1/2 mutation (62%).

Apprehension about the impact of the test result was a more important factor in the reason to decline than concrete burdens such as time to travel to a genetics clinic and time away from work, family, and social obligations.[24] In 15% (n = 31) of individuals from 13 hereditary breast and ovarian cancer families who underwent genetic education and counseling and declined testing for a documented mutation in the family, positive changes in family relationships were reported, specifically greater expressiveness and cohesion, compared with those who pursued testing.[25]

Participation in breast cancer risk counseling among family relatives of breast cancer patients is positively associated with higher levels of education, income, and positive health behaviors (nonsmokers, any current alcohol use, recent clinical breast exam), and perceived and objective risk perception.[26,27] Other predictors of participation are being married, having a family history of cancer, presence of a daughter, fear of stigma, and believing there are more reasons to be tested than not to be tested.[28]

Women recruited from high-risk clinics, i.e., women who have expressed their concern about breast cancer by seeking specialized medical attention, are more likely than women recruited from registry sources to attend counseling and educational sessions about cancer genetics and genetic testing.[16,29] Genetic testing uptake was influenced by eligibility for free testing, history of breast or ovarian cancer, and Ashkenazi Jewish heritage.[14] Interest in testing declines sharply if it is not immediately available.[16] Knowledge about the details of cancer genetic testing is not associated with the decision to be tested,[30] suggesting a need for improved education about cancer genetics. Several studies suggest that interest in cancer genetic testing is generally high despite respondents' relative lack of knowledge regarding the pros and cons of attempting to learn one's mutation status.[27]

There are limited data on uptake of genetic counseling and testing among nonwhite populations, and further research will be needed to define factors influencing uptake in these populations.[29] In a study of African-American women at increased risk of breast cancer, those with a personal history of cancer or a greater perceived risk for developing cancer were more likely to report greater limitations or drawbacks of genetic testing. Those with more fatalistic beliefs about cancer, higher perceived risk of having a BRCA1/2 mutation, and more relatives affected with breast or ovarian cancer were more likely to consider undergoing BRCA1/2 testing.[31] In a case-control study of women who had been seen in a university-based primary care system, African-American women with a family history of breast or ovarian cancer were less likely to undergo BRCA1/2 testing compared with white women who had similar histories. Other predictors of testing used in that study include younger age, higher anxiety, belief that testing will provide reassurance, absence of concern about discrimination, and having had a primary care doctor or gynecologist discuss genetic testing with the patient.[32]

The emerging literature in this area suggests that risk perceptions, health beliefs, psychological status, and personality characteristics are important factors in decision-making about breast/ovarian cancer genetic testing. Many women presenting at academic centers for BRCA1/2 testing arrive with a strong belief that they have a mutation, having decided they want genetic testing, but possessing little information about the risks or limitations of testing.[33] Most mean scores of psychological functioning at baseline for subjects in genetic counseling studies were within normal limits.[34] Nonetheless, a subset of subjects in many genetic counseling studies present with elevated anxiety, depression, or cancer worry.[35] Identification of these individuals is essential to prevent adverse outcomes.

A general tendency to overestimate inherited risk of breast and ovarian cancer has been noted in at-risk populations,[36-38] in cancer patients,[37,39,40] in spouses of breast and ovarian cancer patients,[41] and among women in the general population.[42-44] This tendency may encourage a belief that BRCA1/2 genetic testing will be more informative than it is currently thought to be. There is some evidence that even counseling does not dissuade women at low to moderate risk from the belief that BRCA1 testing could be valuable.[29] Overestimation of both breast and ovarian cancer risk has been associated with nonadherence to physician-recommended screening practices.[45,46] A meta-analysis of 12 studies of outcomes of genetic counseling for breast/ovarian cancer showed that counseling improved the accuracy of risk perception.[47]

Women appear to be the prime communicators within families about the family history of breast cancer.[48] Higher numbers of maternal versus paternal transmission cases are reported,[49] likely due to family communication patterns, to the misconception that breast cancer risk can only be transmitted through the mother, and to the greater difficulty in recognizing paternal family histories because of the need to identify more distant relatives with cancer. Physicians and counselors taking a family history are encouraged to elicit paternal as well as maternal family histories of breast, ovarian, or other associated cancers.[48]

The accuracy of reported family history of breast or ovarian cancer varies; some studies found levels of accuracy above 90%,[50,51] with others finding more errors in the reporting of cancer in second-degree or more distant relatives[52] or in age of onset of cancer.[53] Less accuracy has been found in the reporting of cancers other than breast cancer. Ovarian cancer history was reported with 60% accuracy in one study compared with 83% accuracy in breast cancer history.[54] Providers should be aware that there are a few published cases of Munchausen syndrome in reporting of false family breast cancer history.[55] Much more common is erroneous reporting of family cancer history due to unintentional errors or gaps in knowledge, related in some cases to the early death of potential maternal informants about cancer family history.[48] (Refer to the Taking a Family History section of the Elements of Cancer Genetics Risk Assessment and Counseling summary.)

Targeted written,[56,57] video, CD-ROM, interactive computer program,[58-62] and culturally targeted educational materials [63] may be an effective and efficient means of increasing knowledge about the pros and cons of genetic testing. Such supplemental materials may allow more efficient use of the time allotted for pretest education and counseling by genetics and primary care providers and may discourage ineligible individuals from seeking genetic testing.[56]

Counseling for breast cancer risk typically involves individuals with family histories that are potentially attributable to BRCA1 or BRCA2. It also, however, may include individuals with family histories of Li-Fraumeni Syndrome, ataxia-telangiectasia, Cowden syndrome, or Peutz-Jeghers syndrome.[64] (See the Major Genes section of this summary.)

Management strategies for carriers may involve decisions about the nature, frequency, and timing of screening and surveillance procedures, chemoprevention, risk-reducing surgery, and use of hormone replacement therapy. The utilization of breast conservation and radiation as cancer therapy for women who are carriers may be influenced by knowledge of mutation status. (See the Interventions section of this summary.)

Counseling also includes consideration of related psychosocial concerns and discussion of planned family communication and the responsibility to warn other family members about the possibility of having an increased risk of breast, ovarian, and other cancers. Data are emerging that individual responses to being tested as adults are influenced by the results status of other family members.[65,66] Management of anxiety and distress are important not only as quality-of-life factors, but also because high anxiety may interfere with the understanding and integration of complex genetic and medical information as well as adherence to screening.[17,18,67] The limited number of medical interventions with proven benefit to mutation carriers provides further basis for the expectation that mutation carriers may experience increased anxiety, depression, and continuing uncertainty following disclosure of genetic test results.[68] Formal, objective evaluation of these outcomes are now emerging. (Refer to the sections below on Emotional Outcomes and Behavioral Outcomes.)

Published descriptions of counseling programs for BRCA1 (and subsequently for BRCA2) testing include strategies for gathering a family history, assessing eligibility for testing, communicating the considerable volume of relevant information about breast/ovarian cancer genetics and associated medical and psychosocial risks and benefits, and discussion of specialized ethical considerations about confidentiality and family communication.[3,69-75] Participant distress, intrusive thoughts about cancer, coping style, and social support were assessed in many prospective testing candidates. The psychosocial outcomes evaluated in these programs have included changes in knowledge about the genetics of breast/ovarian cancer after counseling, risk comprehension, psychological adjustment, family and social functioning, and reproductive and health behaviors.[76] A Dutch study of communication processes and satisfaction levels of counselees going through cancer genetic counseling for inherited cancer syndromes indicated that asking more medical questions (by the counselor), providing more psychosocial information, and longer eye contact by the counselor were associated with lower satisfaction levels. The provision of medical information by the counselor was most highly related to satisfaction and perception that needs have been fulfilled.[77] Additional research is needed on how to adequately address the emotional needs and feelings of control of counselees.

Many of the psychosocial outcome studies involve specialized, highly selected research populations, some of which were utilized to map and clone BRCA1 and BRCA2. One such example is K2082, an extensively studied kindred of more than 800 members of a Utah Mormon family in which a BRCA1 mutation accounts for the observed increased rates of breast and ovarian cancer. A study of the understanding that members of this kindred have about breast/ovarian cancer genetics found that, even in breast cancer research populations, there was incomplete knowledge about associated risks of colon and prostate cancer, the existence of options for risk-reducing mastectomy (RRM) and risk-reducing salpingo-oophorectomy (RRSO), and the complexity of existing psychosocial risks.[3] A meta-analysis of 21 studies found that genetic counseling was effective in increasing knowledge and improved the accuracy of perceived risk. Genetic counseling did not have a statistically significant long-term impact on affective outcomes including anxiety, distress, or cancer-specific worry and the behavioral outcome of cancer surveillance activities.[34] These prospective studies, however, were characterized by a heterogeneity of measures of cancer-specific worry and inconsistent findings in effects of change from baseline.[34]

It is not yet clearly established to what extent findings derived from special research populations, at least some of which have long awaited genetic testing for breast/ovarian cancer risk, are generalizable to other populations. For example, there are data to suggest that the BRCA1/2 penetrance estimates derived from these dramatically affected families are substantial overestimates and do not apply to most families presenting for counseling and possible testing.[78]

The few studies conducted to date of psychological outcomes associated with genetic testing for mutations in breast/ovarian cancer predisposition genes have shown low levels of distress among those found to be carriers and even lower levels among noncarriers.[56,79-82] A systematic review found that the studies assessing measures of distress (9 of 11 studies) found no change, or a decrease, in those parameters (including anxiety, depression, general distress, and situation distress) in people who had undergone testing at assessments done at 1 month or less, and 3 to 6 months later.[83] One follow-up study from the United Kingdom measured levels of cancer-related worry, general mental health, risk perception, intrusive or avoidant thoughts, and risk-management behaviors at baseline and 1, 4, and 12 months after results were provided. This study included 202 unaffected women and 59 unaffected men, of whom 91 tested positive and 170 tested negative. Results showed that while female noncarriers had significant (P <.001) reductions in cancer-related worry, female carriers younger than 50 years had an increase in cancer-related worry 1 month posttesting. These levels returned to baseline by 12 months but remained higher than noncarrier levels throughout the 12-month period. Female carriers engaged in more posttest screening than noncarriers (92% vs. 30%) within 12 months of test results disclosure. Thirty carriers had RRM and/or RRSO within the same time period.[84] A slightly smaller subset of this cohort was assessed again for cancer-related worry, general mental, health and risk-management behaviors at 3 years post-genetic test result disclosure. One hundred fifty-four women and 39 males, including 71 carriers and 122 noncarriers, returned the questionnaire. The level of distress and cancer worry was similar between carriers and noncarriers. Female carriers had higher distress levels at 3 years versus 1 year post-disclosure, but their level of cancer worry decreased significantly over the same time period. In female noncarriers, although the level of cancer worry had decreased from baseline to 1 year post-disclosure, these levels returned to baseline by 3 years.[85] The authors, however did not comment on contextual factors that might influence distress and cancer worry levels. Another study reported that, compared with pretest levels, mean scores on 1-year posttest measures of cancer-specific distress and state-anxiety decreased significantly among noncarriers, while scores on these measures as well as on a measure of general distress, did not change among BRCA1/2 carriers.[86] One long-term study of 65 female participants explored the psychosocial consequences of carrying a BRCA1/2 mutation 5 years after genetic testing. Carriers did not differ from noncarriers on several distress measures. Although both groups showed significant increases in depression and anxiety compared with 1 year postdisclosure, these scores remained within normal limits for the general population.[87] Caution is advised by authors of these studies in interpretation of the results as they are all from programs in which results disclosure was preceded by extensive genetic counseling about risks and benefits of BRCA1/2 testing, psychological assessment, and even, occasionally, exclusion of a few individuals who appeared highly distressed.[3] Intrusive thoughts (measured by the Impact of Event Scale [IES]) [88] about cancer diminished after results disclosure for both mutation-positive and mutation-negative individuals in one Dutch study.[89]

A prospective Australian study evaluated the psychological impact of genetic testing at baseline, 7 to 10 days, 4 months, and 12 months in 60 women of Ashkenazi Jewish heritage (ten with breast cancer, 50 unaffected). Of the 43 women who opted to learn their test results, 97% felt pleased to have had the test and, at 12 months of follow-up, none regretted having been tested. Seventeen women opted not to receive their results and had significantly lower levels of breast cancer anxiety than did those who opted to receive their results. Women with no history of cancer who opted to learn their results showed a progressive decrease in breast cancer anxiety over the 12-month study period compared with baseline measures. There was also no statistically significant difference in measures of depression and generalized anxiety from baseline to the follow-up assessments.[90] However, these results must be interpreted in light of the fact that only 7 of 43 women had deleterious mutations.

Despite generally positive findings regarding diminished distress in tested individuals, most studies also report increased distress among small subsets of tested individuals. Most, but not all, of these increases are within the normal range of distress. Increased distress has been noted by individuals receiving both positive and negative test results. Studies suggest that the psychological impact of an individual test result is highly influenced by the test result status of other family members. A 1999 study found that an individual’s response to learning his or her own BRCA1/2 test result was significantly influenced by his or her gender and by the genetic test result status of other family members. Adverse, immediate outcomes were experienced by male carriers who were the first tested in their family or by noncarrier men whose siblings were all positive. In addition, female carriers who were the first in their families to be tested or whose siblings were all negative had significantly higher distress than other female carriers.[65] Another study found that spousal anxiety about genetic testing and supportiveness differentiated the impact of BRCA1/2 test results. When the spouse was highly anxious and unsupportive in style, the mutation carrier had significantly higher levels of distress. These studies illustrate that genetic test results are not received in a vacuum, and that researchers need to consider the context of the tested individual in determining which individuals applying for genetic testing may require additional emotional support.[66]

In another study, depression rates postdisclosure were unchanged for mutation carriers and markedly decreased for noncarriers.[22] An analysis of the distress of individuals receiving BRCA1 results in the context of their siblings' results, however, revealed patterns of response suggesting that certain subgroups of tested individuals have markedly increased levels of distress after disclosure that were not apparent when the analysis focused only on comparing the mean scores for carriers versus noncarriers.[65] Early optimistic findings may not sufficiently reflect the true complexity of response to disclosure of BRCA1/2 test results. Female carriers who had no carrier siblings had distress scores (IES) similar to those found in cancer patients 10 weeks after their diagnosis. The distress of male subjects was highly correlated with the status of their siblings’ test results or lack thereof.[65] One pilot study suggested that women diagnosed more recently were more distressed after counseling.[91] A survey of women enrolled in a high-risk clinic found that heightened levels of distress may be more related to living with the awareness of a familial risk for cancer than with the genetic testing process itself. Obtaining genetic testing may be less stressful than living with the awareness of familial risk for cancer.[92] (Note: For more detailed information about depression and anxiety associated with a cancer diagnosis, refer to the PDQ Supportive Care summaries on Anxiety Disorder; Depression; and Normal Adjustment and the Adjustment Disorders.) Case descriptions have supported the importance of family relationships and test outcomes in shaping the distress of tested individuals.[93,94]

Although there are not yet reports of large-scale studies of the reactions of affected individuals to genetic testing, there are indications from several smaller studies that affected individuals who undergo genetic counseling and testing experience more distress than had been expected by professionals [95,96] and are less able themselves to anticipate the intensity of their reactions following result disclosure.[97] Female mutation carriers who have had breast cancer are often surprised by their high level of risk for ovarian cancer. Women mutation carriers who have had breast cancer worried more than unaffected women about developing ovarian cancer, though, in general, worry about ovarian cancer risk was found to be unrealistically low.[96] In addition, some distress related to the burden of conveying genetic information to relatives has been noted among those who are the first in their families to be tested.[95,98]

Several studies have compared the provision of breast cancer genetics services by different providers and the psychological impact on women at high and low risk for cancer. In a study of 735 women at all levels of risk for hereditary breast/ovarian cancer, the services of a multidisciplinary team of genetics specialists was compared with services provided by surgeons. There were no significant differences between groups in anxiety, cancer worry, or perceived risk.[99] In a Scottish study of 373 participants, an alternative model of cancer genetics services using genetics nurse specialists in community-based services was compared with standard genetics regional services. There was no difference in cancer worry or change in health behaviors between the two groups. Cancer worry decreased for both groups over a 6-month period. Women who dropped out of the study tended to be in the nurse provider arm or were at low risk of breast cancer.[100] In a small U.S. study, an evaluation of nurses and genetic counselors as providers of education about breast cancer susceptibility testing was conducted to compare outcomes of pretest education about breast cancer susceptibility. Four genetic counselors and two nurses completed specialized training in cancer genetics. Women receiving pretest education from nurses were as satisfied with information received and had equal degrees of perceived autonomy and partnership. The study findings suggest that with proper training and supervision, both genetic counselors and nurses can be effective in providing pretest education to women considering genetic susceptibility testing for breast cancer risk.[101]

There has been little empirical research in the communication of risk assessments to individuals at risk of breast/ovarian cancer syndromes. When asked to choose a preferred method, individuals undergoing genetic counseling for breast and ovarian cancer appear to prefer quantitative to qualitative presentation of risk information.[102,103] One study indicated that most women wanted information given both ways.[39] Information about the risk of developing breast cancer among women with a family history of breast cancer may be more accurately recalled when presented as odds ratios rather than in other forms.[104]

There is a small but growing body of literature on the use of decision aids as an adjunct to standard genetic counseling to assist patients in making informed decisions about genetic testing. One study measured the effectiveness of a decision aid for BRCA1/2 genetic testing given to women at the end of their first genetic counseling consultation. At 1 week and 6 months follow-up, the decision aid had no effect on informed choice, post-decisional regret or actual genetic testing decision. However, women who received the decision aid had significantly higher knowledge levels and felt more informed about genetic testing than women who received the control pamphlet. The decision aid also helped those women who did not have their blood drawn for genetic testing at the first visit to clarify their values about their testing decision.[105]

Preferences for delivery of breast cancer genetic testing are reported in one study [103] to include counseling conducted by a genetic counselor (42%) or oncologist (22%) rather than by a primary care physician (6%), nurse (12%), or gynecologist (5%). Patients in that study preferred results disclosure by an oncologist. Younger women especially expressed a need for individual consideration of their personal values and goals or potential emotional reactions to testing; 67% believed emotional support and counseling were a necessary part of posttest counseling. Most women (82%) wanted to be able to self-refer for genetic testing, without a physician referral.

Family communication about genetic testing for cancer susceptibility, and specifically about the results of BRCA1/2 genetic testing, is complex; there are few systematic data available on this topic. Gender appears to be an important variable in family communication and psychological outcomes. One study documented that female carriers are more likely to disclose their status to other family members (especially sisters and children aged 14-18 years) than are male carriers.[106] Among males, noncarriers were more likely than carriers to tell their sisters and children the results of their tests. BRCA1/2 carriers who disclosed their results to sisters had a slight decrease in psychological distress, compared with a slight increase in distress for carriers who chose not to tell their sisters. Findings from other studies suggest that there may be more communication about inherited breast and ovarian cancer risk among female family members than between female and male relatives (e.g., between brothers and sisters and/or mothers and sons).[48,107]

Family communication of BRCA1/2 test results to relatives is another factor affecting participation in testing. There have been more studies of communication with first-degree and second-degree relatives than with more distant family members. One study investigated the process and content of communication among sisters about BRCA1/2 test results.[108] Study results suggest that both mutation carriers and women with uninformative results communicate with sisters to provide them with genetic risk information. Among relatives with whom genetic test results were not discussed, the most important reason given was that the affected women were not close to their relatives. Studies found that women with a BRCA mutation more often shared their results with their mother and adult sisters and daughters than with their father and adult brothers and sons.[109-111] A study that evaluated communication of test results to first-degree relatives at 4 months postdisclosure found that women aged 40 years or older were more likely to inform their parents of test results compared with younger women. Participants also were more likely to inform brothers of their results if the BRCA mutation was inherited through the paternal line.[110] Another study found that disclosure was limited mainly to first-degree relatives, and dissemination of information to distant relatives was problematic.[112] Age was a significant factor in informing distant relatives with younger patients being more willing to communicate their genetic test result.[108,109,112]

A few in-depth qualitative studies have looked at issues associated with family communication about genetic testing. Although the findings from these studies may not be generalizable to the larger population of at-risk persons, they illustrate the complexity of issues involved in conveying hereditary cancer risk information in families.[113] On the basis of 15 interviews conducted with women attending a familial cancer genetics clinic, the authors concluded that while women felt a sense of duty to discuss genetic testing with their relatives, they also experienced conflicting feelings of uncertainty, respect, and isolation. Decisions on whom in the family to inform and how to inform them about hereditary cancer and genetic testing may be influenced by tensions between women's need to fulfill social roles and their responsibilities toward themselves and others.[113] Another qualitative study of 21 women who attended a familial breast and ovarian cancer genetics clinic suggested that some women may find it difficult to communicate about inherited cancer risk with their partners and with certain relatives, especially brothers, because of those persons’ own fears and worries about cancer.[107] This study also suggested that how genetic risk information is shared within families may depend on the existing norms for communicating about cancer in general. For example, family members may be generally open to sharing information about cancer with each other, may selectively avoid discussing cancer information with certain family members to protect themselves or other relatives from negative emotional reactions, or may ask a specific relative to act as an intermediary to disclosure of information to other family members.[114] The potential importance of persons outside the family, such as friends, as both confidantes about inherited cancer risk information and as sources of support for coping with this information was also noted in the study.[107]

A study of 31 mothers with a documented BRCA mutation explored patterns of dissemination to children.[115] Of those who chose to disclose test results to their children, age of offspring was the most important factor. Fifty percent of the children who were told were between ages 20 years and 29 years and slightly more than 25% of the children were aged 19 years or younger. Sons and daughters were notified in equal numbers. More than 70% of mothers informed their children within a week of learning their test result. Ninety-three percent of mothers who chose not to share their results with their children indicated that it was because their children were too young. These findings were consistent with two other studies showing that children younger than 13 years were less likely to be informed about test results compared with older children.[110,116] Another study of 187 mothers undergoing BRCA1/2 testing evaluated their need for resources to prepare for a facilitated conversation about sharing their BRCA1/2 testing results with their children. Seventy-eight percent of mothers were interested in three or more resources, including literature (93%), family counseling (86%), talk to prior participants (79%), and support groups (54%).[116]

A longitudinal study of 153 women self-referred for genetic testing for BRCA1 and BRCA2 mutations and 118 of their partners evaluated communication about genetic testing and distress before testing and at 6 months posttesting.[117] The study found that most couples discussed the decision to undergo testing (98%), most test participants felt their partners were supportive, and most women disclosed test results to their partners (97%, n = 148). Test participants who felt their partners were supportive during pretest discussions experienced less distress after disclosure, and partners who felt more comfortable sharing concerns with test participants pretest experienced less distress after disclosure. Six-month follow-up revealed that 22% of participants felt the need to talk about the testing experience with their partners in the week before the interview. Most participants (72%, n = 107) reported comfort in sharing concerns with their partners, and 5% (n = 7) reported relationship strain as a result of genetic testing. In couples in which the woman had a positive genetic test result, more relationship strain, more protective buffering of their partners, and more discussion of related concerns were reported than in couples in which the woman had a true-negative or uninformative result.[117]

There is a small but growing body of literature regarding psychological effects in men who have a family history of breast cancer and who are considering or have had BRCA testing. A qualitative study of 22 men from 16 high-risk families in Ireland revealed that more men in the study with daughters were tested than men without daughters. These men reported little communication with relatives about the illness, with some men reporting being excluded from discussion about cancer among female family members. Some men in the study also reported actively avoiding open discussion with daughters and other relatives.[118] In contrast, a study of 59 men testing positive for a BRCA1/2 mutation found that most men participated in family discussions about breast and/or ovarian cancer. However, fewer than half of the men participated in family discussions about risk-reducing surgery. The main reason given for having BRCA testing was concern for their children and a need for certainty about whether they could have transmitted the mutation to their children. In this study, 79% of participating men had at least one daughter. Most of these men described how their relationships had been strengthened after receipt of BRCA results, helping communication in the family and greater understanding.[119] Men in both studies expressed fears of developing cancer themselves. Irish men especially reported fear of cancer in sexual organs.

In a study of 212 individuals from 13 hereditary breast and ovarian cancer families who received genetic counseling and were offered BRCA1/2 testing for documented mutation in the family, individuals who were not tested were found 6 to 9 months later to have significantly greater increases in expressiveness and cohesiveness compared with those who were tested. Persons who were randomized to a client-centered versus problem-solving genetic counseling intervention had a significantly greater reduction in conflict, regardless of the test decision.[25]

Many studies have looked at the psychological effects in women of having a high risk of developing cancer, either on the basis of carrying a BRCA1/2 mutation or having a strong family history of cancer. However, few studies have looked at the effects on the partners of such women.

A Canadian study assessed 59 spouses of women found to have a BRCA1/2 mutation. All were supportive of their spouses’ decision to undergo genetic testing and 17% wished they had been more involved in the genetic testing process. Spouses who reported that genetic testing had no impact on their relationship had long-term relationships (mean duration 27 years). Forty-six percent of spouses reported that their major concern was of their partner dying of cancer. Nineteen percent were concerned their spouse would develop cancer and 14% were concerned their children would also be BRCA1/2 mutation carriers.[120]

In a U.S. study, 118 partners of women undergoing genetic testing for mutations in BRCA1 and BRCA2 completed a survey prior to testing and then again 6 months following result disclosure. At 6 months, only 10 partners reported that they had not been told of the test result. Ninety-one percent reported that the testing had not caused strain on their relationship. Partners who were comfortable sharing concerns prior to testing experienced less distress following testing. Protective buffering was not found to impact distress levels of partners.[117]

An Australian study of 95 unaffected women at high risk of developing breast and/or ovarian cancer (13 mutation carriers and 82 with unknown mutation status) and their partners showed that although the majority of male partners had distress levels comparable to a normative population sample, 10% had significant levels of distress that indicated the need for further clinical intervention. Men with a high monitoring coping style and greater perceived breast cancer risk for their wife reported higher levels of distress. Open communication between the men and their partners and the occurrence of a cancer-related event in the wife’s family in the last year were associated with lower distress levels. When men were asked what kind of information and support they would like for themselves and their partners, 57.9% reported that they would like more information about breast and ovarian cancer, and 32.6% said they would like more support in dealing with their partner's risk. Twenty-five percent of men had suggestions on how to improve services for partners of high-risk women, including strategies on how to best support their partner, greater encouragement from healthcare professionals to attend appointments, and meeting with other partners.[121]

A study of Dutch men at increased risk of having inherited a BRCA1 mutation reported a tendency for the men to deny or minimize the emotional effects of their risk status, and to focus on medical implications for their female relatives. Men in these families, however, also reported considerable distress in relation to their female relatives.[122] In another study of male psychological functioning during breast cancer testing, 28 men belonging to 18 different high-risk families (with a 25% or 50% risk of having inherited a BRCA1/2 mutation) participated. The study purpose was to analyze distress in males at risk of carrying a BRCA1/2 mutation who applied for genetic testing. Of the men studied, most had low pretest distress; scores were lowest for men who were optimistic or who did not have daughters. Most mutation carriers had normal levels of anxiety and depression and reported no guilt, though some anticipated increased distress and feelings of responsibility if their daughters developed breast or ovarian cancer. None of the noncarriers reported feeling guilty.[123] In one study,[119] adherence to recommended screening guidelines after testing was analyzed. In this study, more than half of male carriers of mutations did not adhere to the screening guidelines recommended after disclosure of genetic test results. These findings are consistent with those for female carriers of BRCA1/2 mutations.[119,124]

A multicenter U.K. cohort study examined prospective outcomes of BRCA1/2 testing in 193 individuals, of which 20% were men aged 28 to 86 years. Men’s distress levels were low, did not differ among carriers and noncarriers, and did not change from baseline (pre-genetic testing) to the 3-year follow-up. Twenty-two percent of male mutation carriers received colorectal cancer screening and 44% received prostate cancer screening;[85] however, it is unclear whether men in this study were following age-appropriate screening guidelines.

Several studies have explored communication of BRCA test results to at-risk children. Across all studies, the rate of disclosure to children ranging in age from 4 to 25 years is approximately 50%.[109,110,112,116,125-128] In general, age of offspring was the most important factor in deciding whether to disclose test results. In one study of 31 mothers disclosing their BRCA test results, 50% of the children who were informed of the results were aged 20 to 29 years and slightly more than 25% of the children were aged 19 years or younger. Sons and daughters were notified in equal numbers.[115] Similarly, in another study of 42 female BRCA mutation carriers, 83% of offspring older than age 18 years were told of the results, while only 21% of offspring aged 13 years or younger were told.[116]

Several studies have also looked at the timing of disclosure to children after parents receive their test results. Although the majority of children were told within a week to several months after results disclosure,[110,115,116] some parents chose to delay disclosure.[116] Reasons for delaying disclosure included waiting for the child to get older, allowing time for the parent to adjust to the information, and waiting until results could be shared in person (in the case of adult children living away from home).[116]

One study looked at the reaction of children to results disclosure or the effect on the parent-child relationship of communicating the results.[116] With regard to offspring’s understanding of the information, almost half of parents from one study reported that their child did not appear to understand the significance of a positive test result, although older children were reported to have a better understanding. This same study also showed that 48% of parents reported at least one negative reaction in their child, ranging from anxiety or concern (22%) to crying and fear (26%). It should be noted, however, that in this study children's level of understanding and reactions to the test result were measured qualitatively and based only on the parents' perception. Also, given the retrospective design of the study, there was a potential for recall bias. There were no significant differences in emotional reaction depending on age or gender of the child. Lastly, 65% of parents reported no change in their relationship with their child, while 5 parents (22%) reported a strengthening of their relationship.

Another study of 187 mothers undergoing BRCA1/2 testing evaluated their need for resources to prepare for a facilitated conversation about sharing their BRCA1/2 testing results with their children. Seventy-eight percent of mothers were interested in three or more resources, including literature (93%), family counseling (86%), talking to prior participants (79%), and support groups (54%).[129]

Testing for BRCA1/2 has been almost universally limited to adults older than 18 years. The risks of testing children for adult-onset disorders (such as breast and ovarian cancer), as inferred from developmental data on children’s medical understanding and ability to provide informed consent, have been outlined in several reports.[130-133] Surveys of parental interest in testing children for adult-onset hereditary cancers suggest that parents are more eager to test their children than to be tested themselves for a breast cancer gene, suggesting potential conflicts for providers.[134,135] In a general population survey in the United States, 71% of parents said that it was moderately, very, or extremely likely that if they carried a breast-cancer predisposing mutation, they would test a 13-year-old daughter now to determine her breast cancer gene status.[134] To date, no data exist on the testing of children for BRCA1/2, though some researchers believe it is necessary to test the validity of assumptions underlying the general prohibition of testing of children for breast/ovarian cancer and other adult-onset disease genes.[136-138] In one study, 20 children (aged 11 to 17 years) of a selected group of mothers undergoing genetic testing (80% of whom previously had breast cancer and all of whom had discussed BRCA1/2 testing with their children) completed self-report questionnaires on their health beliefs and attitudes toward cancer, feelings related to cancer, and behavioral problems.[139] Ninety percent of children thought they would want cancer risk information as adults; half worried about themselves or a family member developing cancer. There was no evidence of emotional distress or behavioral problems. Another study by this group [127] found that 1 month after disclosure of BRCA1/2 genetic test results, 53% of 42 enrolled mothers of children aged 8 to 17 years had discussed their result with one or more of their children. Age of the child rather than mutation status of the mother influenced whether they were told, as did family health communication style.

In one study, participants who told children younger than 13 years about their carrier status had increased distress, and those who did not tell their young children experienced a slight decrease in distress. Communication with young children was found to be influenced by developmental variables such as age and style of parent/child communication.[127]

Prenatal diagnosis of breast/ovarian cancer predisposition is generally discouraged.[140] Adult age at onset, good prognosis for many breast cancer patients, and the expectation of greater medical progress by the time disease onset might be expected decades into the future make the prospect of prenatal diagnosis an uncomfortable one for many geneticists, leading potentially to charges of eugenics.[134,141] Limited data on the use of this technology are available. In a small series, 26 mutation carriers indicated that pregnancy termination based on mutation status would not be acceptable. Interestingly, a small percentage of nonmutation carriers felt that termination of a pregnancy, where the fetus was a mutation carrier was acceptable.[142] Historically, in Huntington disease, the uptake of prenatal diagnosis and termination is low.[143,144]

The U.K. Human Fertilization and Embryology authority has approved the use of preimplantation genetic diagnosis (PGD) for hereditary breast and ovarian cancer. In a sample of 102 women with a BRCA mutation, most were supportive of PGD but only 38% of the women who had completed their families would consider it for themselves and only 14% of women who were contemplating a future pregnancy would consider it.[145]

The recognition that BRCA1/2 mutations are prevalent, not only in breast/ovarian cancer families but also in some ethnic groups,[146] has led to considerable discussion of the ethical, psychological, and other implications of having one’s ethnicity be a factor in determination of disease predisposition. Fears of genetic reductionism and the creation of a genetic underclass [147] have been voiced. Questions about the impact on the group of being singled out as having genetic vulnerability to breast cancer have been raised. There is also confusion about who gives or withholds permission for the group to be involved in studies of their genetic identity. These issues challenge traditional views on informed consent as a function of individual autonomy.[148]

A growing literature on the unique factors influencing a variety of cultural subgroups suggests the importance of developing culturally specific genetic counseling and educational approaches.[63,149-152]

The human implications of the ethical issues raised by the advent of genetic testing for breast/ovarian cancer susceptibility are described in case studies,[153] essays,[68,154] and research reports. Issues about rights and responsibilities in families concerning the spread of information about genetic risk promise to be major ethical and legal dilemmas in the coming decades.

Studies have shown that 62% of studied family members were aware of the family history, and that 88% of hereditary breast/ovarian cancer family members surveyed have significant concerns about privacy and confidentiality. Expressed concern about cancer in third-degree relatives, or relatives farther removed, was about the same as that for first- or second-degree relatives of the proband.[155] Only half of surveyed first-degree relatives of women with breast or ovarian cancer felt that written permission should be required to disclose BRCA1/2 test results to a spouse or immediate family member. Attitudes toward testing varied by ethnicity, previous exposure to genetic information, age, optimism, and information style. Altruism is a factor motivating genetic testing in some people.[16] Many professional groups have made recommendations regarding informed consent.[16,27,72,156,157] There is some evidence that not all practitioners are aware of or follow these guidelines.[15] Research shows that many BRCA1/2 genetic testing consent forms do not fulfill recommendations by professional groups about the 11 areas that should be addressed,[156] and they omit highly relevant points of information.[15] In a study of women with a history of breast or ovarian cancer, the interviews yielded that the women reported feeling inadequately prepared for the ethical dilemmas they encountered when imparting genetic information to family members.[158] These data suggest that more preparation about disclosure to family members before testing reduces the emotional burden of disseminating genetic information to family members. Patients and health care providers would benefit from enhanced consideration of the ethical issues of warning family members about hereditary cancer risk.

There is a small but growing body of literature on the use of decision aids as an adjunct to standard genetic counseling to assist patients in making informed decisions about cancer risk management. One study showed that the use of a decision aid consisting of individualized value assessment and cancer risk management information after receiving positive BRCA1/2 test results was associated with fewer intrusive thoughts and lower levels of depression at the 6-month follow-up in unaffected women. Use of the decision aid did not alter cancer risk management intentions and behaviors. Slightly detrimental effects on well-being and several decision-related outcomes, however, were noted among affected women.[159] Another study compared responses to a tailored decision aid (including a values-clarification exercise) versus a general information pamphlet intended for women making decisions about ovarian cancer risk management. In the short term, the women receiving the tailored decision aid showed a decrease in decisional conflict and increased knowledge compared with women receiving the pamphlet, but no differences in decisional outcomes were found between the two groups. In addition, the decision aid did not appear to alter the participant’s baseline cancer risk management decisions.[160] A third decision aid focused on breast cancer risk management decision support for women with a BRCA1/2 mutation. Pre-evaluations and postevaluations of the decision aid in 20 women showed that use of the aid resulted in a significant decrease in decisional conflict, improvement in knowledge, and a decrease in uncertainty about tamoxifen use, RRM and RRSO. No significant differences were identified in cancer-related distress following the use of the tool.[161]

An increasing number of studies have examined uptake and adherence to cancer risk management options among individuals who have undergone genetic counseling and testing for BRCA1 and BRCA2 gene mutations. Findings from these studies are reported in Tables 6 and 7. Outcomes and length of follow-up time periods vary across studies, and are reported by mutation carrier or testing status (e.g., mutation-positive, mutation-negative, or declined genetic testing) and include uptake or adherence to screening (mammograply, MRI, CA 125, transvaginal ultrasound) as well as selection of RRM and RRSO.