Introduction
Anticipated and Actual Interest in 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
Cultural/Community Effects
Ethical Concerns
Psychological Aspects of Medical Interventions
Psychosocial Outcome Studies
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 reactions. 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 includes 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]

Anticipated interest in breast cancer genetic testing has overestimated uptake rates for BRCA1 and BRCA2 testing. Interest ranged from 41% to 93%.[11-19] Among samples of women at higher-than-average breast cancer risk seen in clinical and research settings, uptake of testing was lower, ranging from 26% to 78%.[20-27] The discrepancy between interest and uptake on genetic testing for breast cancer is consistent with the literature on colorectal cancer and Huntington’s disease.[28-31]

The level of uptake of genetic testing in research studies is variable, ranging from 26% to 78%.[20,21,24-27] 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.[32] With the advent of clinical testing, it is impossible to measure uptake rates because patients are self-referred. 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 versus lack of an identified mutation).
• Extent to which genetic test results are likely to influence clinical decision-making.[27]

Little is known about the characteristics of at-risk individuals who decline testing. It is difficult to access samples of 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.[25] 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 1 reason for nontesting in most of these women.[33] Other reasons for declining included having no children and becoming acquainted with breast/ovarian cancer in the family relatively early in their lives.[25,33]

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.[17,34] 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.[35] Family communication of BRCA1/2 test results to relatives is another factor affecting participation in testing. For example, it has been observed that in some families in which a mutation is detected, no relatives come forward for predictive genetic testing and distant relatives pursue genetic testing less frequently. 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.[36] 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. Other studies found that women with a BRCA mutation more often shared their results with their adult sisters and daughters than with their adult brothers and sons;[37] and another study found that disclosure was limited mainly to first-degree relatives, and dissemination of information to distant relatives was problematic.[38] Age was a significant factor in informing distant relatives with younger patients being more willing to communicate their genetic test result.[36-38]

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.[39,40] Genetic testing uptake was influenced by eligibility for free testing, history of breast or ovarian cancer, and Ashkenazi Jewish heritage.[27] Interest in testing declines sharply if it is not immediately available.[39] Knowledge about the details of cancer genetic testing is not associated with the decision to be tested,[12] 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.[34] There are limited data on uptake among nonwhite populations, and further research will be needed to define factors influencing uptake in these populations.[40]

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.[41] 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, although the data on this subject are contradictory.[39,42,43] An additional motivation for testing is to receive information that would benefit other family members.[26] Lastly, other motivators for testing may include 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.[44]

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.[45] Most mean scores of psychological functioning at baseline for subjects in genetic counseling studies were within normal limits.[46] Nonetheless, a subset of subjects in many genetic counseling studies present with elevated anxiety, depression, or cancer worry. 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,[47,48] in cancer patients,[19,49,48] in spouses of breast and ovarian cancer patients,[50] and among women in the general population.[51,52] 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.[40] Overestimation of both breast and ovarian cancer risk has been associated with nonadherence to physician-recommended screening practices.[53,54] A meta-analysis of 12 studies of outcomes of genetic counseling for breast/ovarian cancer showed that counseling improved the accuracy of risk perception.[55]

Women appear to be the prime communicators within families about the family history of breast cancer.[56] Higher numbers of maternal versus paternal transmission cases are reported, 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.[56]

The accuracy of reported family history of breast or ovarian cancer varies; some studies found levels of accuracy above 90%,[57,58] with others finding more errors in the reporting of cancer in second-degree or more distant relatives.[59] 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.[60] Providers should be aware that there are a few published cases of Munchausen syndrome in reporting of false family breast cancer history.[61] 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.[56] (Refer to the Taking a Family History section of the Elements of Cancer Genetics Risk Assessment and Counseling summary.)

Targeted written,[62] video, CD-ROM, interactive computer program,[63-65] and culturally targeted educational materials [66] 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.[62]

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’s disease, or Peutz-Jeghers syndrome.[67] (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.[24,68] 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.[42,43,69] 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.[70] 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.[3,71-76] 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.[77]

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 and risk-reducing oophorectomy, 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.[46] These prospective studies, however, were characterized by a heterogeneity of measures of cancer-specific worry and inconsistent findings in effects of change from baseline.[46]

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.[21,62,79] 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.[80] Few studies have conducted longer term follow-up. 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 one year postdisclosure, these scores remained within normal limits for the general population.[81] 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 Events Scale (IES)) [82] about cancer diminished after results disclosure for both mutation-positive and mutation-negative individuals in 1 Dutch study.[83]

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.[24] 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 nonsupportive 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.[68]

In another study, depression rates postdisclosure were unchanged for mutation carriers and markedly decreased for noncarriers.[25] 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.[24] 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.[24] One pilot study suggested that women diagnosed more recently were more distressed after counseling.[84] 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.[85] (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, Psychosocial Distress, and the Adjustment Disorders.) Case descriptions have supported the importance of family relationships and test outcomes in shaping the distress of tested individuals.[86,87]

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 [88,89] and are less able themselves to anticipate the intensity of their reactions following result disclosure.[90] 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.[89] 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.[88,91]

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.[92] 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 2 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.[93] In a small US 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 2 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.[94]

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.[95,96] One study indicated that most women wanted information given both ways.[19] 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.[97]

Preferences for delivery of breast cancer genetic testing are reported in 1 study [96] 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 a significant variable in family communication and psychological outcomes. One study documents 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.[98] 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.

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.[99] 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.[99]

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.[100] In contrast, a study of 59 men testing positive for a BRCA1/2 mutation recruited from Creighton University and the University of Toronto cancer centers 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.[101] Men in both studies expressed fears of developing cancer themselves. Irish men especially reported fear of cancer in sexual organs.

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.[102] 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, although some anticipated increased distress and feelings of responsibility if their daughters developed breast or ovarian cancer. None of the noncarriers reported feeling guilty.[103] In one study,[101] 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.[101,104]

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.[105-107] Surveys of parental interest in testing children for late-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.[108,109] 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.[108] To date, no data exist on the testing of children for BRCA1/2, although 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.[110-112] In 1 study, 20 children (aged 11–17 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.[113] 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 [114] found that 1 month after disclosure of BRCA1/2 genetic test results, 53% of 42 enrolled mothers of children aged 8–17 years had discussed their result with 1 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 1 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.[114]

Prenatal diagnosis of breast/ovarian cancer predisposition is generally discouraged.[115] 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.[108,116] 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 non–mutation carriers felt termination of a pregnancy where the fetus was a mutation carrier was acceptable.[117] Historically, in Huntington’s disease, the uptake of prenatal diagnosis and termination is low.[118,119]

The recognition that BRCA1/2 mutations are prevalent, not only in breast/ovarian cancer families but also in some ethnic groups,[120] 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 [121] 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.[122]

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.[66,123-126]

The above data are associated with the subgroups that have been most intensively studied to date, but there will be an emerging literature on this topic.

The human implications of the ethical issues raised by the advent of genetic testing for breast/ovarian cancer susceptibility are described in case studies,[127] essays,[70,128] 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.[129] 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.[39] Many professional groups have made recommendations regarding informed consent.[34,39,74,130,131] There is some evidence that not all practitioners are aware of or follow these guidelines.[41] 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,[130] and they omit highly relevant points of information.[41] 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.[132] 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.

Risk-reducing mastectomy is 1 of the options for risk reduction recommended for discussion with women who have an increased risk of developing breast cancer due to inherited cancer predisposition.[131] It is also offered to some women with a strong family history of breast cancer who have had, or who are contemplating, removal of 1 breast because of the presence of tumor,[133] and to women with premalignant breast disease or extreme cancer fear.[134] Recommendation for risk-reducing mastectomy has been controversial because of the lack of clarity in criteria for its appropriate use [135] and limited data on the emotional and social ramifications.[136] Reports of >90% risk reduction for women at high and moderate risk for breast cancer strengthen the likelihood that providers will discuss risk-reducing mastectomy with women at increased hereditary risk.[23,137]

Caution is advised in interpreting the value and advisability of risk-reducing mastectomy among women at increased genetic risk because of the need to consider the psychological and other costs of surgery.[138]

On the other hand, many women found to be mutation carriers express interest in risk-reducing mastectomy in hopes of minimizing their risk of breast cancer. In 1 study of a number of unaffected women with no previous risk-reducing surgery who received results of BRCA1 testing following genetic counseling, 17% of carriers (2/12) intended to have mastectomies and 33% (4/12) intended to have oophorectomies.[21] In a later study of the same population, risk-reducing mastectomy was considered an important option by 35% of women who tested positive, whereas risk-reducing oophorectomy was considered an important option by 76%. Initial interest does not always translate into the decision for surgery. One study found that only 3% (½9) of mutation carriers had a risk-reducing mastectomy in the year following result disclosure.[104] In a study of patients in the United Kingdom, data were collected during observations of genetic consultations and in semistructured interviews with 41 women following their attendance at genetic counseling.[139] The option of risk-reducing surgery was raised in 29 consultations and discussed in 35 of the postclinic interviews. Fifteen women said they would consider having an oophorectomy in the future, and 9 said they would consider having a mastectomy. The implications of undergoing oophorectomy and mastectomy were discussed in postclinic interviews. Risk-reducing surgery was described by the counselees as providing individuals with a means to (a) fulfill their obligations to other family members and (b) reduce risk and contain their fear of cancer. The costs of this form of risk management were described by the respondents as:

• Compromising social obligations.
• Upsetting the natural balance of the body.
• Not receiving protection from cancer.
• Operative and postoperative complications.
• The onset of menopause.
• The effects of body image, gender, and personal identity.
• Potential effects on sexual relationships.[139]

A number of women choose to undergo risk-reducing mastectomy and risk-reducing oophorectomy without genetic testing because:

• Testing is not readily accessible.
• They do not wish exposure to the psychosocial risks of genetic testing.
• They do not trust that a negative genetic test result means they are not at increased risk.
• They find any level of risk, even baseline population risk, unacceptable.[140,141]

In an early report, among first-degree relatives of breast cancer patients attending a surveillance clinic, women selecting risk-reducing mastectomy tended to be those with more cancer worry, more previous biopsies, and higher subjective breast cancer risk estimates compared with women who were uninterested in risk-reducing mastectomy.[142] Fourteen women in that study who had undergone risk-reducing mastectomy 6 to 30 months earlier reported overall satisfaction with their surgery decision, but 29% expressed little or no satisfaction with their reconstruction decision.

For the woman having her breasts removed prophylactically, the decision about whether to have reconstruction is often difficult. Despite assurances that reconstruction will not interfere with their detection of any cancer that might develop, some women choose no reconstruction to avoid any continuing worry about a cancer hidden under a reconstructed breast or because of fears about health problems which might develop due to ruptured or leaking implants.

A prospective study conducted in the Netherlands found that among 26 BRCA1/2 mutation carriers, the 14 women who chose mastectomy had higher distress both before test result disclosure and 6 and 12 months later, compared with the 12 carriers who chose surveillance and compared with 53 nonmutation carriers. Overall, however, anxiety declined in women undergoing prophylactic mastectomy; at 1 year, their anxiety scores were closer to those of women choosing surveillance and to the scores of nonmutation carriers.[143] Interestingly, women opting for prophylactic mastectomy had lower pretest satisfaction with their breasts and general body image than carriers who opted for surveillance or noncarriers of BRCA1/2 mutations. Of the women who had a prophylactic mastectomy, all but 1 did not regret the decision at 1 year posttest disclosure, but many had difficulties with body image, sexual interest and functioning, and self-esteem. The perception that doctors had inadequately informed them about the consequences of prophylactic mastectomy was associated with regret.[143] At 5-year follow-up, women who had undergone risk-reducing mastectomy had less favorable body image and changes in sexual relationships, but also had a significant reduction in the fear of developing cancer.[81]

Mixed psychosocial outcomes were reported in a follow-up study (mean 14 years) of 609 women who received prophylactic mastectomies at the Mayo Clinic. Seventy percent were satisfied with prophylactic mastectomy, 11% were neutral, and 19% were dissatisfied. Eighteen percent believed that if they had the choice to make again, they probably or definitely would not have a prophylactic mastectomy. About three quarters said their worry about cancer was diminished by surgery. Half reported no change in their satisfaction with body image; 16% reported improved body image following surgery. Thirty-six percent said they were dissatisfied with their body image following prophylactic mastectomy. About a quarter of the women reported adverse impact of prophylactic mastectomy on their sexual relationships and sense of femininity, and 18% had diminished self-esteem. Factors most strongly associated with satisfaction with prophylactic mastectomy were postsurgical satisfaction with appearance, reduced stress, no reconstruction or lack of problems with implants, and no change or improvement in sexual relationships. Women who cited physician advice as the primary reason for choosing prophylactic mastectomy tended to be dissatisfied following prophylactic mastectomy.[144]

Quality of life in 59 women who underwent risk-reducing oophorectomy was assessed at 24 months postprocedure.[145] Overall quality of life was similar to the general population and breast cancer survivors, with approximately 20% reporting depression. The 30% of subjects reporting vaginal dryness and dyspareunia were more likely to report dissatisfaction with the procedure.

Very little about how the results of genetic testing affect treatment decisions at the time of cancer diagnosis is known. Two studies explored genetic counseling and BRCA1/2 genetic testing at the time of breast cancer diagnosis.[146,147] One of these studies found that genetic testing at the time of diagnosis significantly altered surgical decision making, with more mutation carriers than noncarriers opting for bilateral mastectomy. Bilateral prophylactic mastectomy was chosen by 48% of mutation-positive women [146] and by 100% of mutation-positive women in a smaller series [147] of women undergoing testing at the time of diagnosis. Of women in whom no mutation was found, 24% also opted for bilateral mastectomy.[146] Physician recommendation was an important determinant of surgical decisions.

Several psychological interventions have been proposed for women who may have hereditary risk of breast cancer, but few of these have been rigorously tested. Issues faced by these women include the following:

• Confronting the meaning of one’s risk status, as well as venting strong feelings of fear of harm, disfigurement, pain, or death.
• Addressing guilt about passing on genetic risk or not doing enough for loved ones.
• Managing stress, cancer-related worry, and intrusive thoughts.
• Coaching in problem-solving.
• Facilitating effective decision-making strategies and teaching positive, active coping behaviors.

Psychotherapy for women interested in prophylactic mastectomy is discussed in 1 report.[148] Another recommends rehearsal of affective state in the context of all potential outcomes of cancer genetic testing for BRCA1/2.[149] As genetic testing programs grow and the psychological outcomes and behavioral impact of testing are further defined, there will be an increasing demand for interventions to maximize the benefits of cancer genetic testing and minimize the risks to carriers and family members.

A pilot study demonstrated the usefulness of a 6-session psychoeducational support group for women at high genetic risk of breast cancer who were considering prophylactic mastectomy. The themes for the group sessions included overestimation of and anxiety about risk, desire for “hard data,” emotional impact of watching a mother die of breast cancer, concerns about spouse reactions, self-image and body image, the decision-making process, and confusion over whom to trust in decision-making. Both the participants and the multidisciplinary leaders concluded that as a supplement to individual counseling, a support group is a beneficial and cost-effective treatment modality.[150]

A study [151] of screening behaviors of 216 self-referred, high-risk (>10% risk of carrying a BRCA1/2 mutation) women who are members of hereditary breast cancer families found a range of screening practices. Even the presence of known mutations in their families was not associated with good adherence to recommended screening practices. Sixty-nine percent of women aged 50 to 64 years and 83% of women aged 40 to 49 years had had a screening mammogram in the previous year. Twenty percent of participants had ever had a CA 125 test and 31% had ever had a pelvic or transvaginal ultrasound. Further analysis of this study population [151] looking specifically at 107 women with informative BRCA test results found good use of breast cancer screening, although the uptake rate in younger carriers is lower. The reason for the lower uptake rate was not explored in this study.[152] While motivations cited for pursuing genetic testing often include increased adherence to breast and/or ovarian screening recommendations,[14,17,35,151] limited data exist about how much participants in genetic testing alter their screening behaviors over time and about other variables that may influence those behaviors, such as insurance coverage and physician recommendations or attitudes.

This is a critical issue not only for women testing positive, but also for adherence to screening for those testing negative as well as those who have received indeterminate results or choose not to receive their results. It is possible that adherence actually diminishes with a decrease in the perceived risk that may result from a negative genetic test result.

In addition, while there is still some question regarding the link between cancer-related worry and breast cancer screening behavior, accumulating evidence appears to support a linear rather than a curvilinear relationship. That is, for some time, the data were not consistent; some data supported the hypothesis that mild-to-moderate worry may increase adherence, while excessive worry may actually decrease the utilization of recommended screening practices. Other reports support the notion that a linear relationship is more likely; that is, more worry increases adherence to screening recommendations. Few studies, however, have followed women to assess their health behaviors following genetic testing. Thus, a negative test result leading to decreased worry could theoretically result in decreased screening adherence. A large study found that patient compliance with screening practices was not related to general or screening-specific anxiety—with the exception of breast self-exam, for which compliance is negatively associated with procedure-specific anxiety.[53] Further research designed to clarify this potential concern would highlight the need for comprehensive genetic counseling to discuss the need for follow-up screening.

Further complicating this area of research are issues such as the baseline rate of mammography adherence among women older than 40 or 50 years prior to genetic testing. More specifically, the ability to note a significant difference in adherence on this measure may be affected by the high adherence rate to this screening behavior before genetic testing by women undergoing such testing. It may be easier to find significant changes in mammography use among women with a family history of breast cancer who test positive. Finally, adherence over time will likely be affected by how women undergoing genetic testing and their caregivers perceive the efficacy of many of the screening options in question, such as mammography for younger women, breast self-examination, and ovarian cancer screening (periodic vaginal ultrasound and serum CA 125 measurements), along with the value of preventive interventions.

The issue of screening decision-making and adherence among women undergoing genetic testing for breast and ovarian cancer is the subject of several ongoing trials, and an area of much needed ongoing study.

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