Genetics of Breast and Gynecologic Cancers (PDQ®)–Health Professional Version
Psychosocial Issues in Inherited Breast and Ovarian Cancer Syndromes
Introduction
Psychosocial research in the context of cancer genetic testing helps to define psychological outcomes, interpersonal and familial effects, and cultural and community responses. This type of research also identifies behavioral factors that encourage or impede screening 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.
This section addresses psychosocial issues in hereditary breast and ovarian cancer syndromes. Psychosocial and screening issues related to gynecologic cancers associated with Lynch syndrome are discussed in the Psychosocial Issues in Hereditary Colon Cancer Syndromes section in the PDQ summary on Genetics of Colorectal Cancer.
Uptake of Genetic Counseling and Genetic Testing
Degree of uptake of genetic counseling and genetic testing
Comparison of uptake rates among studies in which counseling and testing were offered is challenging because of differences in methodologies, including the sampling strategy used, the recruitment setting, and testing through a research protocol with high-risk cohorts or kindreds. In a systematic review of 40 studies conducted before 2002 that had assessed genetic testing utilization, uptake rates varied widely and ranged from 25% to 96%, with an average uptake rate of 59%.[1] Results of multivariate analysis found that BRCA1/BRCA2 genetic testing uptake was associated with having a personal or family history of breast or ovarian cancer, and with methodological features of the studies, including sampling strategies, recruitment settings, and how studies defined actual uptake versus the intention to have testing.
Other factors have been positively correlated with uptake of BRCA1/BRCA2 genetic testing, although these findings are not consistent across all studies. Psychological factors that have been positively correlated with testing uptake include greater cancer-specific distress and greater perceived risk of developing breast or ovarian cancer. Having more cancer-affected relatives also has been correlated with greater testing uptake.
Table 14 summarizes the uptake of genetic testing in clinical and research cohorts in the United States.
Several studies conducted in non-U.S. settings have examined the uptake of genetic testing.[7-11] In studies examining the uptake of testing among at-risk relatives of carriers of BRCA1/BRCA2 pathogenic variants, uptake rates have averaged below 50% (range, 36%–48%), with higher uptake reported among female relatives than in male relatives. Other factors associated with higher uptake of testing were not consistently reported among studies but have most commonly included being a parent and wanting to learn information about a child’s risk.
Factors influencing uptake of genetic counseling and genetic testing
In reviews that have examined the cumulative evidence concerning the predictors of uptake of BRCA1/BRCA2 genetic testing, important predictors of testing uptake include older age, Ashkenazi Jewish (AJ) heritage, unmarried status, a personal history of breast cancer, and a family history of breast cancer. Studies recruiting participants in hospital settings had significantly higher recruitment rates than did studies recruiting participants in community settings. Studies that required an immediate decision to test, rather than allowing delayed decision making, tended to report higher uptake rates.[1] However, there is evidence that women diagnosed with breast cancer are equally satisfied with genetic counseling (including information received and strength and timing of physician recommendations for counseling), whether they received genetic counseling before or after their definitive surgery for breast cancer.[12] Another review [13] found that uptake of genetic testing for BRCA1/BRCA2 pathogenic variants was related to psychological factors (e.g., anxiety about breast cancer and perceived risk of breast cancer) and demographic and medical factors (e.g., history of breast cancer or ovarian cancer, presence of children, and higher number of affected first-degree relatives [FDRs]). Family members with a known BRCA1/BRCA2 pathogenic variant were more likely to pursue testing; those with more extensive knowledge of BRCA1/BRCA2 testing, heightened risk perceptions, beliefs that mammography would promote health benefit, and high intentions to undergo testing were more likely to follow through with testing.[14]
In a review of racial/ethnic differences that affect uptake of BRCA1/BRCA2 testing, intention to undergo genetic testing in African American women was related to having at least one FDR with breast cancer or ovarian cancer, higher perceived risk of being a carrier, and less anticipatory guilt about the possibility of being a gene carrier.[15]
Reasons cited for following through with testing included a desire to learn about a child's risk, to feel relief from uncertainty, to inform screening or risk-reducing surgery decisions, and to inform important life decisions such as marriage and childbearing.[14,16] Among African American women, the most important reason for testing included motivation to help other relatives decide on genetic testing.[15]
Physician recommendation may be another motivator for testing. In a retrospective study of 335 women considering genetic testing, 77% reported that they wanted the opinion of a genetics physician about whether they should be tested, and 49% wanted the opinion of their primary care provider.[17] However, there is some evidence of referral bias favoring those with a maternal family history of breast cancer or ovarian cancer. In a Canadian retrospective review of 315 patients, those with a maternal family history of breast cancer or ovarian cancer were 4.9 times (95% confidence interval, 3.6–6.7) more likely to be referred for a cancer genetics consultation by their physician than were those with a paternal family history (P < .001).[18] Studies have found that physicians may not adequately assess paternal family history [19] or may underestimate the significance of a paternal family history for genetic risk.[19-21] Other studies have shown that physician referral of patients who meet U.S. Preventive Services Task Force guidelines for BRCAgenetic counseling has been suboptimal.[22]
The uptake of BRCA testing to inform surgical treatment decisions when offered appears to be high in research cohorts;[2,23] however, findings from other studies suggest that testing is underutilized in clinical practice to inform breast cancer treatment decisions.[6,24,25] Barriers to the use of BRCA testing to inform surgical treatment decisions, including lack of physician referral of newly diagnosed patients for genetic counseling, type of insurance coverage, and challenges in the timing and coordination of testing, have been reported.[6,26-28]
Insurance coverage
Insurance coverage is an important consideration for individuals deciding whether to undergo genetic testing. (Refer to the Insurance coverage section in the PDQ summary on Cancer Genetics Risk Assessment and Counseling for more information.)
Uptake of genetic counseling and genetic testing in diverse populations
Degree of uptake of genetic counseling and genetic testing in diverse populations
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] The uptake of BRCA testing appears to vary across some racial/ethnic groups. A few studies have compared uptake rates between African American and white women.[4,30] In a case-control study of women who had been seen in a university-based primary care system, African American women with family histories of breast cancer or ovarian cancer were less likely to undergo BRCA1/BRCA2 testing than were white women who had similar histories.[30] In another study among breast cancer patients who were counseled about BRCA1/BRCA2 risk in a clinical setting, lower uptake was reported among African American women than among white women.[4]
Notably, the racial differences observed in these studies do not appear to be explained by factors related to cost, access to care, risk factors for carrying a BRCA1 or BRCA2 pathogenic variant, or differences in psychosocial factors, including risk perceptions, worry, or attitudes toward testing.
Factors influencing uptake of genetic counseling and genetic testing in diverse populations
Several studies have examined uptake or “acceptance” of BRCA testing among African Americans enrolled in genetic research programs. Among study enrollees from an African American kindred in Utah, 83% underwent BRCA1 testing.[31] Age, perceived risk of being a carrier, and more extensive cancer knowledge predicted testing acceptance. Another study that recruited African American women through physician and community referrals reported a BRCA1/BRCA2 testing acceptance rate of 22%.[32] Predictors of test acceptance included having a higher probability of having a pathogenic variant, being married, and being less certain about one’s cancer risk. Finally, a third study that recruited at-risk African American women from an urban cancer screening clinic found that acceptors of BRCA testing were more knowledgeable about breast cancer genetics and perceived fewer barriers to testing, including negative emotional reactions, stigmatization concerns, and family-related guilt.[33] While these are independent predictors of genetic testing uptake, they do not explain the disparities in testing uptake across different ethnic groups. What may explain these differences are several attitudes and beliefs held about testing by individuals from diverse populations.
Work examining attitudes toward breast cancer genetic testing in Latino and African American populations indicates limited knowledge and awareness about testing but a generally receptive view once they are informed; in comparison with whites, Latino and African American populations have relatively more concerns about testing.
For example, in a qualitative study with 51 Latino individuals unselected for risk status, important findings included the fact that participants were highly interested in genetic testing for inherited cancer susceptibility, despite very limited knowledge about genetics. One important barrier involved secrecy or embarrassment about family discussions of cancer and genetics, which could be addressed in intervention strategies.[34] Another qualitative study with 54 Latina women at risk of hereditary breast cancer showed that knowledge about BRCA1/BRCA2 counseling was low, although the women were interested in learning more about counseling to gain risk information for family members. Barriers to counseling included life demands, cost, and language issues.[35]
A telephone survey of 314 patients from an inner-city network of Pittsburgh, Pennsylvania, health centers, 50% of whom were African American, found that most participants (57%) (both African Americans and whites) felt that genetic testing to evaluate disease risk was a good idea; however, more African Americans than whites thought that genetic testing would lead to racial discrimination (37% vs. 22%, respectively) and that genetics research was unethical and tampered with nature (20% vs. 11%, respectively).[36] Finally, in a study of 222 women in Savannah, Georgia, where most had neither a personal history (70%) nor a family history (60%) of breast cancer, African American women (who comprised 26% of the sample) were less likely to be aware of breast cancer genes and genetic testing. Awareness was also related to higher income, higher education level, and having a family breast cancer history. However, 74% of the entire sample expressed willingness to be tested for breast cancer susceptibility.[37]
In a sample of 146 African American women meeting criteria for BRCA1/BRCA2 pathogenic variant testing, women born outside the United States reported higher levels of anticipated negative emotional reactions (e.g., fear, hopelessness, and lack of confidence that they could emotionally handle testing). Higher levels of breast cancer–specific distress were associated with anticipated negative emotional reactions, confidentiality concerns, and anticipated guilt regarding the family impact of breast cancer genetic testing.[38] A future orientation (e.g., "I often think about how my actions today will affect my health when I am older") was associated with overall perceived benefits of breast cancer genetic testing in this population (n = 140); however, future orientation was also found to be positively associated with family-related cons of testing, including family guilt and worry regarding the impact of testing on the family.[39]
There are racial differences in provider discussion and patient uptake of genetic testing for variants in BRCA1/BRCA2. A study of women aged 18 to 64 years and diagnosed with invasive breast cancer between 2007 and 2009 found that, even after adjusting for pathogenic variant risk, African American women were less likely to report having received a physician recommendation for genetic testing. There was no difference across all races in concerns that BRCA1/BRCA2 testing was too expensive and only minimal differences in testing attitudes or insurance concerns were found, none of which influenced testing uptake.[40] A study of breast or ovarian cancer survivors (N = 50) eligible for BRCA1/BRCA2genetic testing found that 48% were referred for genetic counseling and testing and/or had undergone genetic testing. Individuals with higher breast cancer genetics knowledge and higher self-efficacy were more likely to have engaged in genetic counseling and testing.[41] In a study of women with invasive breast cancer diagnosed before age 50 years between 2009 and 2012, all of whom were eligible for BRCA1/BRCA2 genetic testing based on existing guidelines, African Americans were less likely to report a discussion with their health care provider and undergo genetic testing. Uptake of risk-reducing salpingo-oophorectomy (RRSO), risk-reducing mastectomy (RRM), and risk management screening was also consistently lower in African American women.[42]
Factors associated with declining genetic counseling and testing
There is evidence that primary reasons for declining testing involves being childless, which reduces any family motivations for testing; and concerns about the negative ramifications of testing, including difficulty retaining insurance or concerns about personal health.
Limited data are available about the characteristics of at-risk individuals who decline to be tested or have never been tested. It is difficult to access samples of test decliners because they may be reluctant to participate in research studies. Studies of genetic testing uptake 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 who completed a baseline interview regarding testing declined to be tested. Most individuals who declined testing chose not to participate in educational sessions. Decliners were more likely to be male and be unmarried, and have fewer relatives with breast cancer. 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.[43]
Another study looked at a small number (n = 13) of women decliners who carried a 25% to 50% probability of harboring a BRCA pathogenic variant; these nontested women were more likely to be childless and to have higher levels of education. This study showed that most women 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 by most of these women.[44] Other reasons for declining included having no children and becoming acquainted with breast/ovarian cancer in the family relatively early in their lives.[43,44]
A third study evaluated characteristics of 34 individuals who declined BRCA1/BRCA2 testing in a large multicenter study in the United Kingdom. Decliners were younger than 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/BRCA2 pathogenic variant 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/BRCA2 pathogenic variant (62%).
Apprehension about the impact of the test result was a more important factor in the decision to decline testing than were concrete burdens such as time required to travel to a genetics clinic and time spent away from work, family, and social obligations.[45] 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 pathogenic variant in the family, positive changes in family relationships were reported—specifically, greater expressiveness and cohesion—compared with those who pursued testing.[46]
Genetic counseling and testing in children
Testing for BRCA1/BRCA2 pathogenic variants 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 cancers, as inferred from developmental data on children’s medical understanding and ability to provide informed consent, have been outlined in several reports.[47-50]
Studies suggest that persons who have undergone BRCA1/BRCA2 genetic testing or who are adult offspring of persons who have had testing are generally not in favor of testing minors.[51,52] Although the data are limited, research suggests that males, pathogenic variant noncarriers, and those whose mothers did not have personal histories of breast cancer may be more likely to favor genetic testing in minors in general.[51] Of those who had minor children at the time the study was conducted, only 17% stated a preference for having their own children tested. Concerns regarding testing of minors included psychological risks and insufficient maturity. Potential benefits included the ability to influence health behaviors.[52]
No data exist on the testing of children for BRCA1/BRCA2 pathogenic variants, although some researchers believe it is necessary to test the validity of assumptions underlying the general prohibition of testing children for genetic variants associated with breast and ovarian cancers and other adult-onset diseases.[53-55] In one study, 20 children (aged 11–17 y) of a selected group of mothers undergoing genetic testing (80% of whom previously had breast cancer and all of whom had discussed BRCA1/BRCA2 testing with their children) completed self-report questionnaires on their health beliefs and attitudes toward cancer, feelings related to cancer, and behavioral problems.[56] 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.
What People Bring to Genetic Testing: Impact of Risk Perception, Health Beliefs, and Personality Characteristics
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/BRCA2 testing arrive with a strong belief that they have a pathogenic variant, having decided they want genetic testing, but possessing little information about the risks or limitations of testing.[57] Most mean scores of psychological functioning at baseline for subjects in genetic counseling studies were within normal limits.[58] Nonetheless, a subset of subjects in many genetic counseling studies present with elevated anxiety, depression, or cancer worry.[59,60] Identification of these individuals is essential to prevent adverse outcomes. In a study of 205 women pursuing genetic counseling, interactions among cancer worry, breast cancer risk perception, and perceived severity of having a breast cancer genetic variant were found such that those with high worry, high breast cancer risk perception, and low perceived severity were twice as likely to follow through with BRCA1/BRCA2 testing than others.[61]
A general tendency to overestimate inherited risk of breast and ovarian cancer has been noted in at-risk populations,[62-65] in cancer patients,[63,66,67] in spouses of breast and ovarian cancer patients,[68] and among women in the general population.[69-71] but underestimation of breast cancer risk in higher-risk and average-risk women also has been reported.[72] This overestimation may encourage a belief that BRCA1/BRCA2 genetic testing will be more informative than it is currently thought to be. Some evidence exists that even counseling does not dissuade women at low to moderate risk from the belief that BRCA1testing could be valuable.[29] Overestimation of both breast and ovarian cancer risk has been associated with nonadherence to physician-recommended screening practices.[73,74] A meta-analysis of 12 studies of outcomes of genetic counseling for breast/ovarian cancer showed that counseling improved the accuracy of risk perception.[75]
Women appear to be the prime communicators within families about the family history of breast cancer.[76] Higher numbers of maternal versus paternal transmission cases are reported,[77] 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. In an analysis of 2,505 women participating in the Family Healthware Impact Trial,[78] not only was evidence of underreporting of paternal family history identified, but also women reported a lower level of perceived breast cancer risk with a paternal versus maternal breast cancer family history.[79] Physicians and counselors taking a family history are encouraged to elicit paternal and maternal family histories of breast, ovarian, or other associated cancers.[76]
The accuracy of reported family history of breast or ovarian cancer varies; some studies found levels of accuracy above 90%,[80,81] with others finding more errors in the reporting of cancer in second-degree or more distant relatives [82] or in age of onset of cancer.[83] 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.[84] Providers should be aware that there are a few published cases of Munchausen syndrome in reporting of false family breast cancer history.[85] 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.[76] (Refer to the Taking a Family History section of the Cancer Genetics Risk Assessment and Counseling summary for more information.)
Targeted written,[86,87] video, CD-ROM, interactive computer programs and websites,[88-95] and culturally targeted educational materials [96-98] may be effective and efficient methods 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 individuals without appropriate indication of risk from seeking genetic testing.[86]
Genetic Counseling for Hereditary Predisposition to Breast Cancer
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.[99] (Refer to the High-Penetrance Breast and/or Gynecologic Cancer Susceptibility Genes section of this summary for more information.)
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 (HRT). The utilization of breast conservation and radiation as cancer therapy for women who are carriers may be influenced by knowledge of pathogenic variant status. (Refer to the Clinical Management of Carriers of BRCA Pathogenic Variants section of this summary for more information.)
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 suggest that individual responses to being tested as adults are influenced by the results status of other family members.[100,101] 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 and adherence to screening.[102-104] Formal, objective evaluation of these outcomes are well documented. (Refer to the Emotional Outcomes and Behavioral Outcomes sections of this summary for more information.)
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.[105-112] 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.[113] 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.[114]
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 pathogenic variant 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 RRM and RRSO, and the complexity of existing psychosocial risks.[105] 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.[58] These prospective studies, however, were characterized by a heterogeneity of measures of cancer-specific worry and inconsistent findings in effects of change from baseline.[58]
Emotional Outcomes
Although there were initial concerns about the possibility of adverse emotional consequences from BRCA testing, most studies conducted over the years have shown low levels of psychological distress among both carriers and noncarriers, particularly over the longer term.[115-117] In a meta-analysis examining cancer-specific distress over short (0–4 weeks), moderate (5–24 weeks), and long (25–52 weeks) periods of time since the receipt of testing results, carriers were found to demonstrate increased levels of distress shortly after receiving results, with levels returning to baseline within moderate and long periods of time.[115] In contrast, noncarriers and those with inconclusive results showed reduced levels of distress over time.[115,118] Psychological distress patterns were found to vary as a function of several factors, including the cancer history of the individual and the country within which the study was conducted. Carriers with a personal history of cancer experienced small decreases in distress over time, whereas no changes were observed among carriers without a personal history of cancer. Among individuals with inconclusive results, greater decreases in distress were observed among those without a cancer history than among those with a cancer history. Among noncarriers, those in the United States experienced significantly greater decreases in psychological distress than noncarriers from Europe and Australia. A study conducted in Austria noted that certain subgroups of counselees experienced greater distress, including those who were older, had a more recent cancer diagnosis, or those who had received counseling but declined BRCA testing.[119]
Several studies have reported on emotional outcomes over longer follow-up periods (i.e., greater than 12 months after disclosure) than those reported in the meta-analysis described above.[115] In a U.K. study, cancer-related worry did not differ between carriers and noncarriers at 3 years of follow-up.[120] Two U.S.-based studies published since the meta-analytic review [115] have reported similar findings among women who were surveyed more than 3 years after receipt of BRCA test results.[121,122] In a cross-sectional study,[121] 167 women who were surveyed more than 4 years after receiving BRCA test results reported low levels of genetic testing–specific concerns, as measured using the Multidimensional Impact of Cancer Risk Assessment Scale.[123] In multivariate regression models, carriers of pathogenic variants were significantly more likely to experience distress than were noncarriers. In a second study,[122] 464 women were followed prospectively for a median of 5 years (range, 3.4–9.1 y) after testing. Among both affected and unaffected participants, BRCA carriers reported significantly higher levels of distress, uncertainty (affected only), perceived stress (affected only), and lower positive testing experiences (unaffected only) than women who received negative results for a known pathogenic variant in the family.[122] Although both studies [121,122] reported greater distress among BRCA carriers than among noncarriers, the level of distress was not reflective of clinically significant dysfunction.
Although most studies have reported that a positive BRCA test result has a relatively minimal impact on psychological distress, many of these studies were conducted among families with a strong family history of breast or ovarian cancer who underwent extensive pretest genetic counseling. Therefore, emotional responses may not generalize to individuals who test under different contexts. For example, individuals who are tested with population BRCA screening may not have a family history of cancer.[124-126] Although pretest genetic counseling is recommended, this is not always done when genetic testing is ordered by nongenetic providers [127] or directly through commercial companies.[128,129]
For example, in a Canadian study of 2,080 Jewish women who participated in a population-based genetic screening study to test for three BRCA pathogenic variants common in families of Jewish heritage, women were not offered in-person genetic counseling but were given a pamphlet on genetic testing for BRCA1/BRCA2 before they provided a DNA sample. One year after genetic testing, women who were positive for a pathogenic variant (n = 18) showed significant increases in cancer-specific distress, whereas no changes in distress were observed among women who were negative for a pathogenic variant.[125] The mean distress score on the Impact of Event Scale for the 18 women with a known pathogenic variant was 25.3 (range, 2–51); 10 of 18 women (56%) scored within moderate (26–43) (n = 7) or severe (44+) (n = 3) ranges. It is unclear from this study whether the increase in distress observed at 1 year of follow-up was due to the lack of in-person genetic counseling, or whether the lower levels of distress at baseline observed were because the women in the study were low risk but eligible for testing because of their ancestry. A follow-up study with this cohort found that distress decreased between 1 to 2 years after testing and that changes in distress varied by risk-reduction options undertaken by carriers. Specifically, those who had undergone risk-reducing mastectomy or oophorectomy experienced significant decreases in distress compared with those who did not have either surgery.[126] Another smaller qualitative study also supports these findings.[130]
Similarly, the impact of direct-to-consumer (DTC) BRCA testing through commercial companies requires further evaluation. Case studies have reported adverse emotional responses after receipt of a positive BRCA result from DTC genetic testing, suggesting the need for further evaluation of the emotional outcomes of women undergoing genetic testing through commercial companies.[128,129] Only one study, conducted by a commercial company, has attempted to evaluate the impact of BRCA testing in this context.[131] A total of 32 individuals (16 women and 16 men) who tested positive for one of three BRCA founder pathogenic variants common in Ashkenazi Jews completed semi-structured interviews. None of the carriers reported extreme anxiety, although some experienced moderate anxiety (13%) or initial disappointment and anxiety that dissipated over time (28%). These findings should be interpreted with caution given that only 24% (32 of 136) of invited carriers of BRCA pathogenic variants participated in the study, raising concerns about selection bias.
Despite evidence of a short-term increase in distress after the receipt of genetic testing results, any adverse responses to a positive carrier status dissipate within 12 months.[115] Additional research is needed to examine emotional outcomes for those who are not provided genetic counseling before testing.[127]
Emotional outcomes of recently diagnosed individuals
It is becoming increasingly common for women to pursue genetic counseling and testing at the time of diagnosis, but there are limited studies examining psychological outcomes after testing in newly diagnosed women. Although concerns have been raised about the adverse psychological implications of offering rapid genetic counseling and testing between diagnosis and surgery,[132,133] other studies,[134-136] including a randomized trial, [137] have provided evidence indicating no additional adverse psychological effects in newly diagnosed breast cancer patients. However, qualitative research on 20 newly diagnosed breast cancer patients found that some subgroups of these patients may have more difficulty coping with BRCA test results, such as carriers who have no family history of cancer; those who do not have an affected relative with whom they can identify; and higher risk women who receive uninformative negative BRCA results.[132]
Family Effects
Family communication about genetic testing and hereditary risk
Family communication about genetic testing for cancer susceptibility, and specifically about the results of BRCA1/BRCA2 genetic testing, is complex. Gender appears to be an important variable in family communication and psychological outcomes. Studies have documented that female carriers are more likely to disclose their status to other family members (especially sisters and children aged 14–18 y) [138] than are male carriers.[138,139] Among males, noncarriers were more likely than carriers to tell their sisters and children the results of their tests. BRCA1/BRCA2 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. One study found that men reported greater difficulty disclosing a known pathogenic variant to family members than women (90% vs. 70%).[140]
Family communication of BRCA1/BRCA2 test results to relatives is another factor affecting participation in testing. There have been more studies of communication with FDRs and second-degree relatives than with more distant family members. Studies have investigated the process and content of communication among sisters about BRCA1/BRCA2 test results.[141,142] Study results suggest that both carriers of pathogenic variants [141] and women with uninformative results [141,142] communicate with sisters to provide them with genetic risk information. Similar findings were reported in women with uninformative results disclosing test results to their daughters.[142] 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 [141] or had a poor relationship with them.[142] Studies found that women with a BRCA pathogenic variant more often shared their results with their mother and adult sisters and daughters than with their father and adult brothers and sons.[76,143-146] A study that evaluated communication of test results to FDRs 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 pathogenic variant was inherited through the paternal line.[144] Another study found that disclosure was limited mainly to FDRs, and dissemination of information to distant relatives was problematic.[147] Age was a significant factor in informing distant relatives with younger patients being more willing to communicate their genetic test result.[141,143,147] Additionally, one study found that lower genetic worry, higher interest in genomic information, carrying a BRCA1 or BRCA2pathogenic variant, or having never been married was associated with communication to more family members.[139] In contrast, a longer time interval since diagnosis was associated with communication to fewer family members.[139]
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.[148] 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 about 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.[148] 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.[146] 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.[149] 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.[146]
A study of 31 mothers with a documented BRCA pathogenic variant explored patterns of dissemination to children.[150] 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 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. 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 three other studies showing that children younger than 13 years were less likely to be informed about test results compared with older children.[144,151,152] Another study of 187 mothers undergoing BRCA1/BRCA2 testing evaluated their need for resources to prepare for a facilitated conversation about sharing their BRCA1/BRCA2 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%).[151]
A longitudinal study of 153 women self-referred for genetic testing for BRCA1 and BRCA2pathogenic variants and 118 of their partners evaluated communication about genetic testing and distress before testing and at 6 months posttesting.[153] 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.[153]
A study of 561 FDRs of women who had undergone BRCA1/BRCA2 genetic testing found that 22% of FDRs did not recall being informed of the genetic test results despite the women reporting that the results had been shared.[154] Men were less likely to recall receiving the results (P > .001). Of those with recall about receiving the test results, 10.5% of FDRs did not recall the findings. For those with recall of the results, 17.9% of FDRs had an interpretation that was discordant with the correct results. Accuracy of test results recall was greater for informative test results (those that were either true positive or true negative) (P = .029). However, regardless of the test results, FDRs perceived the cancer risk to be higher before they learned of the findings than after (74% and 53% of FDRs reported that they believed their risk for cancer was greater than average before and after hearing test results, respectively).
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.[155] In contrast, a study of 59 men testing positive for a BRCA1/BRCA2 pathogenic variant 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 pathogenic variant 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.[156] Men in both studies expressed fears of developing cancer themselves. Irish men especially reported fear of cancer in sexual organs.
Family functioning
One study assessed 212 individuals from 13 hereditary breast and ovarian cancer families who received genetic counseling and were offered BRCA1/BRCA2 testing for documented pathogenic variants in the family. Individuals who were not tested were found 6 to 9 months later to have significantly greater increases in family expressiveness and cohesiveness compared with those who were tested. Persons who were randomly assigned to a client-centered versus problem-solving genetic counseling intervention had a significantly greater reduction in conflict, regardless of the test decision.[46]
Partners of high-risk women
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/BRCA2 pathogenic variant or having a strong family history of cancer. Some studies have also examined the effects on the partners of such women.
A Canadian study assessed 59 spouses of women found to have a BRCA1/BRCA2 pathogenic variant. 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 carriers of BRCA1/BRCA2 pathogenic variants.[157]
In a U.S. study, 118 partners of women who underwent genetic testing for pathogenic variants in BRCA1 and BRCA2 completed a survey before testing and then again 6 months after 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 before testing experienced less distress after testing. Protective buffering was not found to impact distress levels of partners.[153]
An Australian study of 95 unaffected women at high risk of developing breast and/or ovarian cancer (13 carriers of pathogenic variants and 82 with unknown variant 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 wives 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 health care professionals to attend appointments, and meeting with other partners.[158]
A review of this literature reported that the BRCA testing process may be distressing for male partners, particularly for those with spouses identified as carriers. Male partner distress appears to be associated with their beliefs about the woman’s breast cancer risk, lack of couple communication, and feelings of alienation from the testing process.[159]
At-risk males
A review of the literature on the experiences of males in families with a known BRCA1 and BRCA2 pathogenic variant reported that while the data are limited, men from variant-positive families are less likely than females to participate in communication regarding genetics at every level, including the counseling and testing process. Men are less likely to be informed of genetic test results received by female relatives, and most men from these families do not pursue their own genetic testing.[160]
A study of Dutch men at increased risk of having inherited a BRCA1 pathogenic variant 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.[161] 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/BRCA2 pathogenic variant) participated. The study purpose was to analyze distress in males at risk of carrying a BRCA1/BRCA2 pathogenic variant 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 carriers of pathogenic variants 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.[162] In one study,[156] adherence to recommended screening guidelines after testing was analyzed. In this study, more than half of male carriers of pathogenic variants 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/BRCA2 pathogenic variants.[156,163]
A multicenter U.K. cohort study examined prospective outcomes of BRCA1/BRCA2 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 (before genetic testing) to the 3-year follow-up. Twenty-two percent of male carriers of pathogenic variants received colorectal cancer screening and 44% received prostate cancer screening;[120] however, it is unclear whether men in this study were following age-appropriate screening guidelines.
Children
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%.[143,144,147,151,164-167] 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.[150] Similarly, in another study of 42 female carriers of BRCA pathogenic variants, 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.[151]
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,[144,150,151] some parents chose to delay disclosure.[151] 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).[151]
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.[166]
One study looked at the reaction of children to results disclosure or the effect on the parent-child relationship of communicating the results.[151] 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.
Interestingly, a large multicenter study of 869 mother-daughter pairs (the daughters were aged 6 to 13 y) found that girls with a family history of breast cancer or a familial BRCA1/BRCA2 pathogenic variant (BCFH+) compared with those without such family histories had better psychosocial adjustment by maternal report.[168] However, based on a combination of maternal report and direct assessment of girls aged 10 to 13 years, BCFH+ girls experienced greater breast cancer–specific distress and a higher perceived risk of breast cancer than their peers without such family histories. Moreover, higher daughter distress was associated with higher maternal distress. A similarly designed study in older girls, aged 11 to 19 years, found that higher breast cancer–specific distress in daughters was associated with perceived risk and maternal distress. This older age group had higher self-esteem than did their peers without a family history of breast cancer.[169]
Another study of 187 mothers undergoing BRCA1/BRCA2 testing evaluated their need for resources to prepare for a facilitated conversation about sharing their BRCA1/BRCA2 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%).[170]
Testing for BRCA1/BRCA2 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.[47-50] 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.[171,172] 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 pathogenic variant, they would test a 13-year-old daughter now to determine her breast cancer gene status.[171] To date, no data exist on the testing of children for BRCA1/BRCA2, 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.[53-55] In one study, 20 children (aged 11–17 y) of a selected group of mothers undergoing genetic testing (80% of whom previously had breast cancer and all of whom had discussed BRCA1/BRCA2 testing with their children) completed self-report questionnaires on their health beliefs and attitudes toward cancer, feelings related to cancer, and behavioral problems.[56] 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 [166] found that 1 month after disclosure of BRCA1/BRCA2 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 pathogenic variant status of the mother influenced whether they were told, as did family health communication style.
Prenatal diagnosis and preimplantation genetic diagnosis
The possibility of transmitting a pathogenic variant to a child may pose a concern to families affected by hereditary breast and ovarian cancer (HBOC),[173] perhaps to the extent that some carriers may avoid childbearing.[174,175] These concerns also may prompt women to consider using prenatal diagnosis methods to help reduce the risk of transmission.[173,176] Prenatal diagnosis is an encompassing term used to refer to any medical procedure conducted to assess the presence of a genetic disorder in a fetus. Methods include amniocentesis and chorionic villous sampling (CVS).[177,178] Both procedures carry some risk of miscarriage and some evidence suggests fetal defects may result from using these tests.[177,178] Moreover, discovering the fetus is a carrier for a genetic defect may impose a difficult decision for couples regarding pregnancy continuation or termination. An alternative to these tests is preimplantation genetic diagnosis (PGD), a procedure used to test fertilized embryos for genetic disorders before uterine implantation,[173,179,180] thereby avoiding the potential dangers associated with amniocentesis and CVS and the decision to terminate a pregnancy. Using the information obtained from the genetic testing, potential parents can decide whether or not to implant. PGD can be used to detect pathogenic variants in hereditary cancer predisposing genes, including BRCA.[173,176]
In the United States, a series of studies has evaluated awareness, interest (e.g., would consider using PGD), and attitudes related to PGD among members of Facing Our Risk of Cancer Empowered (FORCE), an advocacy organization focused on persons at increased risk of HBOC.[173,176,181] The first study was a Web-based survey of 283 members,[173] the second included 205 attendees of the 2007 annual FORCE conference,[176] and the third was a Web-based survey of 962 members.[181,182] These studies have documented low levels of awareness, with 20% to 32% of study respondents reporting having heard of PGD before study participation.[176,181] With respect to interest in PGD, the first study [173] found only 13% of women would be likely to use PGD, whereas, 33% of respondents in the subsequent FORCE studies reported that they would consider using PGD.[176,181] In the third FORCE-based study (n = 962),[181] multivariable analysis revealed PGD interest was associated with the desire to have more children, having previously had any prenatal genetic test, and previous awareness of PGD. Attitudinal predictors of interest in PGD included agreement that others at risk of HBOC should be offered PGD; the belief that PGD is acceptable for persons at risk of HBOC; the belief that PGD information should be given to individuals at risk of HBOC; and endorsement of PGD benefits of having children without genetic variants and eliminating genetic diseases. Conversely, those who indicated that PGD was “too much like playing God” and reported that they considered PGD in the context of religion, had less interest in PGD.
It is unknown whether the attitudes of FORCE members toward PGD are representative of the majority of BRCA carriers. One study of 171 clinic-based patients from a single U.S. institution who tested positive for a BRCA pathogenic variant found that approximately 20% (33 of 168) were aware of PGD; 72% (122 of 169) thought PGD should be offered; and 41% (65 of 158) would consider PGD.[183]
The U.K. Human Fertilization and Embryology authority has approved the use of PGD for hereditary breast and ovarian cancer. In a sample of 102 women with a BRCA pathogenic variant, most were supportive of PGD but only 38% of the women who had completed their families would consider it for themselves had PGD been available, and only 14% of women who were contemplating a future pregnancy would consider PGD.[184] In a study of 77 individuals undergoing BRCA testing as part of a multicenter cohort study in Spain, 61% of respondents reported they would consider PGD. Factors associated with PGD interest were age 40 years and older and had a prior cancer diagnosis.[185]
In France, couples who obtain authorization from a multidisciplinary prenatal diagnosis team may access PGD free of charge as a benefit of their national health care system. However, no BRCA carriers have been authorized to use PGD. In a national study of 490 unaffected carriers of BRCA pathogenic variants of childbearing age (women aged 18–49 y; men aged 18–69 y), 16% stated that BRCA test results had altered their ongoing plans for childbearing.[186] Upon qualitative analysis of written comments provided by some respondents, the primary impact was related to accelerating the timing of pregnancy, feelings of guilt about possibly passing on the pathogenic variant to offspring, and having future children. In response to a hypothetical scenario in which PGD was readily available, 33% of participants reported that they would undergo PGD. Factors associated with this intention were having no future reproductive plans at the time of the survey, feeling pregnancy termination was an acceptable option in the context of identifying a BRCApathogenic variant, and having fewer cases of breast and/or ovarian cancer in the family. When presented with questions about expectations about delivery of PGD or prenatal diagnosis (PND) information, 85% of respondents felt it should be provided along with BRCA test results; 45% felt that it should be provided when carriers decide to have children. Respondents stated that they would expect this information to be delivered by cancer geneticists (92%), obstetrician/gynecologists (76%), and general practitioners (48%).
A small (N = 25) qualitative study of women of reproductive age positive for a BRCApathogenic variant who underwent genetic testing before having children evaluated how their BRCA status influenced their attitudes about reproductive genetic testing (both PGD and PND) and decisions about having children.[187] In this study, the decision to undergo BRCA testing was primarily motivated by the desire to manage one’s personal cancer risk, rather than a desire to inform future reproductive decisions. The perceived severity of HBOC influenced concerns about passing on a BRCA pathogenic variant to children and also influenced willingness to consider PGD or PND and varied based on personal experience. Most did not believe that a known BRCA pathogenic variant was a reason to terminate a pregnancy. As observed in prior studies, knowledge of reproductive options varied; however, there was a tendency among participants to view PGD as more acceptable than PND with regard to termination of pregnancy. Decisions regarding the pros and cons of PGD versus PND with termination of pregnancy were driven primarily by personal preferences and experiences, rather than by morality judgments. For example, women were deterred from PGD based on the need to undergo in vitro fertilization and to take hormones that might increase cancer risk and based on the observed experiences of others who underwent this procedure.
One study has examined these issues among high-risk men recruited from FORCE and Craigslist (a bulletin board website) (N = 228).[188] Similar to the previous studies of women, only 20% of men were aware of PGD before survey participation. In a multivariate analysis, those who selected the “other” option for possible benefits of PGD compared with those who selected from several predetermined options (e.g., having children without genetic variants) and those who considered PGD in the context of religion (as opposed to health and safety) were less likely to report that they would ever consider using PGD.
Cultural/Community Effects
The recognition that BRCA1/BRCA2 pathogenic variants are prevalent, not only in breast/ovarian cancer families but also in some ethnic groups,[189] 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. Concerns that people will think everything is solely determined by genetic factors and the creation of a genetic underclass [190] 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.[191]
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.[96,192-196] The inclusion of members within the community of interest (e.g., breast cancer survivors, advocates, and community leaders) may enhance the development of culturally tailored genetic counseling materials.[97] One study showed that participation in any genetic counseling (culturally mediated or standard approaches) reduced perceived risk of developing breast cancer.[197]
Ethical Concerns
The human implications of the ethical issues raised by the advent of genetic testing for breast/ovarian cancer susceptibility are described in case studies,[198] essays,[199,200] 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.[201] Only half of surveyed FDRs of women with breast or ovarian cancer felt that written permission should be required to disclose BRCA1/BRCA2 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.[202] Many professional groups have made recommendations regarding informed consent.[109,202-205] There is some evidence that not all practitioners are aware of or follow these guidelines.[206] Research shows that many BRCA1/BRCA2 genetic testing consent forms do not fulfill recommendations by professional groups about the 11 areas that should be addressed,[207] and they omit highly relevant points of information.[206] 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.[208] 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. (Refer to the PDQ summaries Cancer Genetics Risk Assessment and Counseling and Cancer Genetics Overview for more information about the ethics of cancer genetics and genetic testing.)
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
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.[209-213] One study showed that the use of a decision aid consisting of individualized value assessment and cancer risk management information after receiving positive BRCA1/BRCA2 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.[211] 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.[210] A multisite randomized trial of 150 unaffected women with BRCA1/BRCA2 pathogenic variants assessed the effect of a decision aid on breast cancer risk management decisions and psychosocial outcomes. At 6-month and 12-month follow-up, women randomly assigned to the decision aid had lower levels of cancer-related distress (P = .01 at 6 months and P = .05 at 12 months) than did the control group.[213] Decisional conflict scores were relatively low at baseline and declined over time in both groups; the scores between the two groups were not statistically different.
Uptake of cancer risk management options
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 pathogenic variants. Findings from these studies are reported in Table 15 and Table 16. Outcomes vary across studies and include uptake or adherence to screening (mammography, magnetic resonance imaging [MRI], cancer antigen [CA] 125, transvaginal ultrasound [TVUS]) and selection of RRM and RRSO. Studies generally report outcomes by pathogenic variant carrier or testing status (e.g., positive for pathogenic variants, negative for pathogenic variants, or declined genetic testing). Follow-up time after notification of genetic risk status also varied across studies, ranging from 12 months up to several years.
Findings from these studies suggest that breast screening often improves after notification of BRCA1/BRCA2 pathogenic variant carrier status; nonetheless, screening remains suboptimal. Fewer studies have examined adoption of MRI as a screening modality, probably due to the recent availability of efficacy data. Screening for ovarian cancer varied widely across studies, and also varied based on type of screening test (i.e., CA-125 serum testing vs. TVUS screening). However, ovarian cancer screening does not appear to be widely adopted by carriers of BRCA1/BRCA2 pathogenic variants. Uptake of RRM varied widely across studies, and may be influenced by personal factors (such as younger age or having a family history of breast cancer), psychosocial factors (such as a desire for reduction of cancer-related distress), recommendations of the health care provider, and cultural or health care system factors. An individual’s choice to have a bilateral mastectomy also appears to be influenced by pretreatment genetic education and counseling regardless of the genetic test results.[214] Similarly, uptake of RRSO also varied across studies, and may be influenced by similar factors, including older age, personal history of breast cancer, perceived risk of ovarian cancer, cultural factors (i.e., country), and the recommendations of the health care provider.
On the other hand, many women found to be pathogenic variant carriers express interest in RRM in hopes of minimizing their risk of breast cancer. In one study of a number of unaffected women with no previous risk-reducing surgery who received results of BRCA1testing after genetic counseling, 17% of carriers (2 of 12) intended to have mastectomies and 33% (4 of 12) intended to have oophorectomies.[230] In a later study of the same population, RRM was considered an important option by 35% of women who tested positive, whereas risk-reducing oophorectomy was considered an important option by 76%. A prospective study assessed the stability of risk management preferences over five time points (pre-BRCA testing to 9 months after results disclosure) among 80 Dutch women with a documented BRCA pathogenic variant. Forty-six participants indicated a preference for screening at baseline. Of 25 women who preferred RRM at baseline, 22 indicated the same preference 9 months after test results disclosure; however, it was not reported how many women actually had RRM.[231]
Initial interest does not always translate into the decision for surgery. Two different studies found low rates of RRM among carriers of pathogenic variants in the year after result disclosure, one showing 3% (1 of 29) of carriers and the other 9% (3 of 34) of carriers having had this surgery.[163,232] Among members from a large BRCA1 kindred, utilization of cancer screening and/or risk-reducing surgeries was assessed at baseline (before disclosure of results), and at 1 year and 2 years after disclosure of BRCA1 test results. Of the 269 men and women who participated, complete data were obtained on 37 female carriers and 92 female noncarriers, all aged 25 years or older. At 2 years after disclosure of test results, none of the women had undergone RRM, although 4 of the 37 carriers (10.8%) said they were considering the procedure. In contrast, of the 26 women who had not had an oophorectomy before baseline, 46% (12 of 26) had obtained an oophorectomy by 2 years after testing. Of those carriers aged 25 to 39 years, 29% (5 of 17) underwent oophorectomy, while 78% (7 of 9) of the carriers aged 40 years and older had this procedure.[215] In a study assessing uptake of risk-reducing surgery 3 months after BRCAresult disclosure, 7 of 62 women had undergone RRM and 13 of 62 women had undergone RRSO. Intent to undergo RRSO before testing correlated with procedure uptake. In contrast, intent to undergo RRM did not correlate with uptake. Overall, reasons given for indecision about risk-reducing surgery included complex testing factors such as the significance of family history in the absence of a pathogenic variant, concerns over the surgical procedure, and time and uncertainty regarding early menopause and the use of HRT.[233] In a U.K. study, data were collected during observations of genetic consultations and in semistructured interviews with 41 women after they received genetic counseling.[234] 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 nine 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 follows:
- 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.[234]
A number of women choose to undergo RRM and RRSO without genetic testing because of the following:
Among FDRs of breast cancer patients attending a surveillance clinic, women who expressed an interest in RRM and/or had undergone surgery were found to have significantly more breast cancer biopsies (P < .05) and higher subjective 10-year breast cancer risk estimates (P < .05) than women not interested in RRM. Cancer worry at the time of entry into the clinic was highest among women who subsequently underwent RRM compared with women who expressed interest but had not yet had surgery and women who did not intend to have surgery (P < .001).[237]
BRCA testing, when offered to women newly diagnosed with breast cancer, has been shown to influence surgical decision making in that carriers are more likely to opt for bilateral mastectomy compared with noncarriers.[214,238,239] A study that evaluated predictors of contralateral RRM among 435 breast cancer survivors found that 16% had undergone contralateral RRM (in conjunction with mastectomy of the affected breast) before referral for genetic counseling and BRCA1/BRCA2 genetic testing.[240] Predictors of contralateral RRM before genetic counseling and testing included younger age at breast cancer diagnosis, more time since diagnosis, having at least one affected FDR, and not being employed full-time. In the year after disclosure of test results, 18% of women who tested positive for a BRCA1/BRCA2 pathogenic variant and 2% of those whose test results were uninformative underwent contralateral RRM. Predictors of contralateral RRM after genetic testing included younger age at breast cancer diagnosis, higher cancer-specific distress before genetic counseling, and having a positive BRCA1/BRCA2 test result. In this study, contralateral RRM was not associated with distress at 1 year after disclosure of genetic test results. A retrospective chart review evaluated uptake of bilateral mastectomies in 110 women who underwent BRCA1/BRCA2 genetic testing before making surgical decisions about the treatment of newly diagnosed breast cancer. Carriers of BRCApathogenic variants were more likely to undergo bilateral mastectomies than were women in whom no variant was detected (83% vs. 37%; P = .046).[241] The only predictor of contralateral RRM in women without a pathogenic variant was being married (P = .03). Age, race, parity, disease stage and biomarkers, increased mammographic breast density, and breast MRI did not influence contralateral RRM decisions at the time of primary surgical treatment.
A study conducted from 2006 to 2014 in 11 U.S. academic and community centers of 897 women, aged 40 years and younger at breast cancer diagnosis, found that rates of BRCAgenetic testing have increased over time.[239] Within 1 year after diagnosis, 87% of the sample underwent BRCA testing. The rate increased from 77% of newly diagnosed women tested in 2006 to 95% of women tested in 2013. Among women who tested positive for a pathogenic BRCA variant and stated that testing affected their surgery decisions (n = 88), 86% underwent bilateral mastectomy compared with 51% of noncarriers (P < .001). Among untested women, about one-third reported that they were not told by a health care provider that they were candidates for BRCA testing; yet, according to national guidelines, all were eligible for testing solely on the basis of their age at diagnosis.
Dutch women (N = 114) who had undergone unilateral or bilateral RRM with breast reconstruction between 1994 and 2002 were retrospectively surveyed to determine their satisfaction with the procedure.[242] Sixty-eight percent were either unaffected carriers ofBRCA pathogenic variants or at a 50% risk of having a BRCA pathogenic variant in their family. Sixty percent of respondents indicated that they were satisfied with the procedure, 95% would opt for RRM again, and 80% would opt for the same reconstruction procedure. Less than half reported some perioperative or postoperative complications, ongoing physical complaints, or some physical limitations. Twenty-nine percent reported altered feelings of femininity after the procedure, 44% reported adverse changes in their sexual relationships, and 35% indicated that they believed their partners experienced adverse changes in their sexual relationship. Ten percent of women, however, reported positive changes in their sexual relationship after the procedure. Compared with patients who indicated satisfaction with this procedure, nonsatisfied patients were more likely to feel less informed about the procedure and its consequences, report more complications and physical complaints, feel that their breasts did not belong to their body, and indicate that they would not opt for reconstruction again. Those who reported a negative effect on their sexual relationship were more likely to:
- Feel less informed.
- Experience more physical complaints and limitations.
- Express that their breasts did not feel like their own.
- Be disinclined to opt for reconstruction again.
- State that the surgery had not met their expectations.
- Experience altered feelings of femininity and perceived adverse changes in their partner’s view of their femininity and their sexual relationship.
Ninety Swedish women who had undergone RRM between 1997 and 2005 were surveyed before surgery, 6 months after surgery, and 1 year after surgery to evaluate changes in health-related quality of life, depression, anxiety, sexuality, and body image. There were no significant changes in health-related quality of life or depression at the three time points; anxiety decreased over time (P = .0004). More than 80% of women reported having an intimate relationship at all three time points. Women who reported being sexually active were asked to respond to questions about sexual pleasure, discomfort, habit, and frequency of activity. There were no statistically significant differences related to frequency, habit, or discomfort. However, pleasure significantly decreased between baseline and 1 year after surgery (P = .005). At 1 year after surgery, 48% of women reported feeling less attractive, 48% reported feeling self-conscious, and 44% reported dissatisfaction with surgical scars.[243]
Discussion of risk-reducing surgical options may not consistently occur during pretest genetic counseling. In one multi-institutional study, only one-half of genetics specialists discussed RRM and RRSO in consultations with women from high-risk breast cancer families,[244,245] despite the fact that discussion of surgical options was significantly associated with meeting counselees’ expectations, and that such information was not associated with increased anxiety.[246]
Given the increased risk of ovarian cancer faced by women with a BRCA1 or BRCA2pathogenic variant, those who do receive information about RRSO show wide variations in surgery uptake (27%–72%).[9,120,224,227,247,248] A study showed that clinical factors related to choosing RRSO versus surveillance alone are older age, parity of one or more, and a prior breast cancer diagnosis.[249] In this study, the choice of RRSO was not related to family history of breast or ovarian cancer. Hysterectomy was presented as an option during genetic counseling, and 80% of women who underwent RRSO also elected to have a hysterectomy.
Cancer screening and risk-reducing behaviors
Data are now emerging regarding uptake and adherence to cancer risk management recommendations such as screening and risk-reducing interventions. Cancer screening adherence and risk-reduction behaviors as defined by the National Comprehensive Cancer Network Guidelines were assessed in a cross-sectional study of 214 women with a personal history (n = 134) or family history (n = 80) of breast or ovarian cancer. Among unaffected women older than 40 years, 10% had not had a mammogram or clinical breast examination (CBE) in the previous year and 46% did not practice breast self-examination (BSE). Among women previously affected with breast or ovarian cancer, 21% had not had a mammogram, 32% had not had a CBE, and 39% did not practice BSE.[250]
Three hundred and twelve women who were counseled and tested for BRCA pathogenic variants between 1997 and 2005 responded to a survey regarding their perception of genetic testing for hereditary breast and ovarian cancer. The survey included questions on risk reduction options, including screening and risk-reducing surgeries. Two hundred and seventeen (70%) of the women had been diagnosed with breast cancer, and 86 (28%) tested positive for a pathogenic variant in either the BRCA1 or BRCA2 gene. None of the BRCA-positive women agreed that mammograms are difficult procedures because of the discomfort, while 11 (5.4%) of the BRCA-negative women did agree with this statement. Both groups (BRCA-positive and BRCA-negative) agreed that risk-reducing surgeries provide the best means for lowering cancer risk and worry, and most patients in both groups expressed the belief that risk-reducing mastectomy is not too drastic, too scary, or too disfiguring.[251]
A prospective study from the United Kingdom examined the psychological impact of mammographic screening in 1,286 women aged 35 to 49 years who have a family history of breast cancer and were participants in a multicenter screening program. Mammographic abnormalities that required additional evaluation were detected in 112 women. These women, however, did not show a statistically significant increase in cancer worry or negative psychological consequences as a result of these findings. The 1,174 women who had no mammographic abnormality detected experienced a decrease in cancer worry and a decrease in negative psychological consequences compared with baseline after receipt of their results. At 6 months, the entire cohort had experienced a decrease in measures of cancer worry and psychological consequences of breast screening.[252]
A qualitative study explored health care professionals’ views regarding the provision of information about health protective behaviors (e.g., exercise and diet). Seven medical specialists and ten genetic counselors were interviewed during a focus group or individually. The study reported wide variation in the content and extent of information provided about health-protective behaviors and in general, participants did not consider it their role to promote such behaviors in the context of a genetic counseling session. There was agreement, however, about the need to form consensus about provision of such information both within and across risk assessment clinics.[253]
Not all studies specify whether screening uptake rates fall within recommended guidelines for the targeted population or the specific clinical scenario, nor do they report on other variables that may influence cancer screening recommendations. For example, women who have a history of atypical ductal hyperplasia would be advised to follow screening recommendations that may differ from those of the general population.
Psychosocial Outcome Studies
Risk-reducing mastectomy
A prospective study conducted in the Netherlands found that among 26 carriers of BRCA1/BRCA2 pathogenic variants, 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 women negative for a pathogenic variant. Overall, however, anxiety declined in women undergoing risk-reducing mastectomy (RRM); at 1 year, their anxiety scores were closer to those of women choosing surveillance and to the scores of women negative for a pathogenic variant.[254] Interestingly, women opting for RRM had lower pretest satisfaction with their breasts and general body image than carriers who opted for surveillance or noncarriers of BRCA1/BRCA2 pathogenic variants. Of the women who had a RRM, all but one 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 RRM was associated with regret.[254] At the 5-year follow-up, women who had undergone RRM had less favorable body image and changes in sexual relationships, but also had a significant reduction in the fear of developing cancer.[255] In a study of 78 women who underwent risk-reducing surgery (including BRCA1/BRCA2 carriers and women who were from high-risk families with no detectable BRCA1/BRCA2 pathogenic variant), cancer-specific and general distress were assessed 2 weeks before surgery and at 6 and 12 months postsurgery.[256] The sample included women who had RRM and RRSO alone and women who had both surgeries. There was no observable increase in distress over the 1-year period.
Mixed psychosocial outcomes were reported in a follow-up study (mean 14 years) of 609 women who received RRM at the Mayo Clinic. Seventy percent were satisfied with RRM, 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 RRM. About three-quarters said their worry about cancer was diminished by surgery. One-half reported no change in their satisfaction with body image; 16% reported improved body image after surgery. Thirty-six percent said they were dissatisfied with their body image after RRM. About one-quarter of the women reported adverse impact of RRM on their sexual relationships and sense of femininity, and 18% had diminished self-esteem. Factors most strongly associated with satisfaction with RRM 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 RRM tended to be dissatisfied after RRM.[257]
A study of 60 healthy women who underwent RRM measured levels of satisfaction, body image, sexual functioning, intrusion and avoidance, and current psychological status at a mean of 4 years and 4 months postsurgery. Of this group, 76.7% had either a strong family history (21.7%) or carried a BRCA1 or BRCA2 pathogenic variant (55%). Overall, 97% of the women surveyed were either satisfied (17%) or extremely satisfied (80%) with their decision to have RRM, and all but one participant would recommend this procedure to other women. Most women (66.7%) reported that surgery had no impact on their sexual life, although 31.7% reported a worsening sexual life, and 76.6% reported either no change in body image or an improvement in body image, regardless of whether reconstruction was performed. Worsening self-image was reported by 23.3% of women after surgery. Women’s mean distress levels after surgery were only slightly above normal levels, although those women who continued to perceive their postsurgery breast cancer risk as high had higher mean levels of global and cancer-related distress than those who perceived their risk as low. Additionally, carriers of BRCA1 and BRCA2 pathogenic variants and women with a strong family history of breast and/or ovarian cancer had higher mean levels of cancer-related distress than women with a limited family history.[258]
Very little is known about how the results of genetic testing affect treatment decisions at the time of cancer diagnosis. Two studies explored genetic counseling and BRCA1/BRCA2genetic testing at the time of breast cancer diagnosis.[23,214] One of these studies found that genetic testing at the time of diagnosis significantly altered surgical decision making, with more pathogenic variant carriers than noncarriers opting for bilateral mastectomy. Bilateral RRM was chosen by 48% of women with a known pathogenic variant [214] and by 100% of women with a known pathogenic variant in a smaller series [23] of women undergoing testing at the time of diagnosis. Of women in whom no pathogenic variant was found, 24% also opted for bilateral RRM. Four percent of the test decliners also underwent bilateral RRM. Among carriers of pathogenic variants, predictors of bilateral RRM included whether patients reported that their physicians had recommended BRCA1/BRCA2 testing and bilateral RRM before testing, and whether they received a positive test result.[214] Data are lacking on quality-of-life outcomes for women who undergo RRM after genetic testing that is performed at the time of diagnosis.
A prospective study from the Netherlands evaluated long-term psychological outcomes of offering women with breast cancer genetic counseling and, if indicated, genetic testing at the onset of breast radiation for treatment of their primary breast cancer. Of those who were approached for counseling, some underwent genetic testing and chose to receive their result (n = 58), some were approached but did not fulfill referral criteria (n = 118), and some declined the option of counseling/testing (n = 44). Another subset of women undergoing radiation therapy was not approached for counseling (n = 182) but was followed using the same measures. Psychological distress was measured at baseline and at 4, 11, 27, and 43 weeks after initial consultation for radiation therapy. No differences were detected in general anxiety, depression or breast cancer–specific distress across all four groups.[259]
A retrospective questionnaire study of 583 women with a personal and family history of breast cancer and who underwent contralateral RRM between 1960 and 1993 measured overall satisfaction after mastectomy and factors influencing satisfaction and dissatisfaction with this procedure.[260] The mean time of follow-up was 10.3 years after risk-reducing surgery. Overall, 83% of all participants stated they were satisfied or very satisfied, 8% were neutral, and 9% were dissatisfied with contralateral RRM. Most women also reported favorable effects or no change in their self-esteem, level of stress, and emotional stability after surgery (88%, 83%, and 88%, respectively). Despite the high levels of overall satisfaction, 33% reported negative body image, 26% reported a reduced sense of femininity, and 23% reported a negative effect on sexual relationships. The type of surgical procedure also affected levels of satisfaction. The authors attributed this difference to the high rate of unanticipated reoperations in the group of women having subcutaneous mastectomy (43%) versus the group having simple mastectomy (15%) (P < .0001). Limitations to this study are mostly related to the time period during which participants had their surgery (i.e., availability of surgical reconstructive option).[260,261] None of these women had genetic testing for pathogenic variants in the BRCA1/BRCA2genes. Nevertheless, this study shows that while most women in this group were satisfied with contralateral RRM, all women reported at least one adverse outcome.
A retrospective survey of 137 BRCA carriers examined the psychosocial impact of preserving the nipple-areolar complex (NAC) in women with bilateral RRM.[262] The study found that body image and sexual well-being differed significantly based on the type of RRM the women underwent. Women with NAC preservation were more satisfied with their breasts (72% vs. 61%), were more satisfied with the surgical outcome (85% vs. 74%), and had greater sexual well-being (68% vs. 52%) than women without NAC preservation. No differences in cancer-related distress, anxiety, depression, or risk perceptions were observed between the two groups. Oncologic outcomes of nipple-sparing mastectomy in BRCA carriers have not been inferior to RRM without NAC preservation.[263] (Refer to the RRM section of this summary for more information.)
Another study compared long-term quality-of-life outcomes in 195 women after bilateral RRM performed between 1979 and 1999 versus 117 women at high risk of breast cancer opting for screening. No statistically significant differences were detected between the groups for psychosocial outcomes. Eighty-four percent of those opting for surgery reported satisfaction with their decision. Sixty-one percent of women from both the surgery and screening groups reported being very much or quite a bit contented with their quality of life.[264]
In a study of psychosocial outcomes associated with RRM and immediate reconstruction, 61 high-risk women (27 carriers of pathogenic variants, others with high-risk family history), 31 of whom had a prior history of breast cancer, were evaluated on average 3 to 4 years after surgery.[265] The study utilized questions designed to elicit yes versus no responses and found that the surgery was well-tolerated with 83% of participants reporting that the results of their reconstructive surgery were as they expected, 90% reporting that they had received adequate preoperative information, none reporting that they regretted the surgery, and all reporting that they would choose the same route if they had to do it again. Satisfaction with the results ranged from 74% satisfied with the shape of their breasts to 89% satisfied with the appearance of the scarring. Comparison of this group to normative samples on quality-of-life indicators (Short Form 36 Health Survey Questionnaire [SF-36]; Hospital Anxiety and Depression Scale questionnaire scores) indicated no reductions in quality of life in these women.
A qualitative study examining material on the FORCE website posted by 21 high-risk women (BRCA1/BRCA2 positive) undergoing RRM showed that these women anticipated and received negative reactions from friends and family regarding the surgery, and that they managed disclosure in ways to maintain emotional support and self-protection for their decision. Many of the women expressed a relief from intrusive breast cancer thoughts and worry, and were satisfied with the cosmetic result of their surgery.[266]
In contrast, another study examined long-term psychosocial outcomes in 684 women who had had bilateral or contralateral RRM on average 9 years before assessment.[267] A majority of women (59%) also had reconstructive surgery. Interestingly, based on a Likert scale, 85% of women reported that they were satisfied or very satisfied with their decision to have an RRM. However, in qualitative interviews, a large number of women went on to describe dissatisfaction or negative psychosocial outcomes associated with surgery. The authors coded the responses as negative when women reported still being anxious about their breast cancer risk and/or reported negative feelings about their body image, pain, and sexuality. Seventy-nine percent of the women providing negative comments and 84% of those making mixed comments (mixture of satisfaction and dissatisfaction) responded that they were either satisfied or very satisfied with their decision. Twice as many women with bilateral mastectomy made negative and mixed comments than did women with contralateral mastectomy. The areas of most concern were body image, problems with breast implants, pain after surgery, and sexuality. The authors proposed that those who had undergone contralateral procedures had already been treated for cancer, while those who had undergone bilateral procedures had not been treated previously, and this may partially account for the differences in satisfaction between the two groups. These findings suggest that women's satisfaction with RRM may be tempered by their complex reactions over time.
In a qualitative study of 108 women who underwent or were considering RRM, more than half of those who had RRM felt that presurgical consultation with a psychologist was advisable; nearly two-thirds thought that postsurgical consultation was also appropriate. All of the women who were considering RRM believed that psychological consultation before surgery would facilitate decision-making.[268]
Risk-reducing salpingo-oophorectomy
A retrospective self-administered survey of 40 women aged 35 to 74 years at time of RRSO (57.5% were younger than 50 y), who had undergone the procedure through the Ontario Ministry of Health due to a family history of ovarian cancer, found that RRSO resulted in a significant reduction in perceived ovarian cancer risk. Fifty-seven percent identified a decrease in perceived risk as a benefit of RRSO (35% did not comment on RRSO benefits) and 49% reported that they would repeat RRSO to decrease cancer risk. The overall quality-of-life scores were consistent with those published for women who are menopausal or participating in hormone studies.[269] Quality of life in 59 women who underwent RRSO was assessed at 24 months postprocedure.[270] 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.
A Canadian prospective study examined the impact of RRSO on menopausal symptoms and sexual functioning before surgery and then 1 year later in a sample of 114 women with known BRCA1/BRCA2 pathogenic variants.[271] Satisfaction with the decision to undergo RRSO was high regardless of symptoms reported. Those who were premenopausal at the time of surgery (n = 75) experienced a worsening of symptoms and a decline in sexual functioning. HRT addressed vaginal dryness and dyspareunia but not declines in sexual pleasure. HRT also resulted in fewer moderate to severe hot flashes.
Additional work reported by this group found that the majority of the 127 women who had undergone RRSO 1 year previously (75 with BRCA1 pathogenic variants; 52 with BRCA2pathogenic variants) felt that RRSO reduced their risk of both breast and ovarian cancer.[272] There was a wide range of risk perceptions for ovarian cancer noted in the group. Twenty percent of carriers of BRCA1 and BRCA2 pathogenic variants thought that their risk of ovarian cancer was completely eliminated; others had an inflated perception of their ovarian cancer risk both before and after surgery. A small group of these women were further surveyed at about 3 years postsurgery, and their risk perceptions did not change significantly during this extended time period. These findings suggest that important misperceptions about ovarian cancer risk may persist after RRSO. Additional genetic education and counseling may be warranted.
A larger study assessed quality of life in women at high risk of ovarian cancer who opted for periodic gynecologic screening (GS) versus those who underwent RRSO. Eight hundred forty-six high-risk women, 44% of whom underwent RRSO and 56% of whom chose GS, completed questionnaires evaluating quality of life, cancer-specific distress, endocrine symptoms, and sexual functioning.[273] Women in the RRSO group were a mean of 2.8 ±1.9 years from surgery and women in the GS group were a mean of 4.3 years from their first visit to a gynecologist for high-risk management. No statistical difference in overall quality of life was detected between the RRSO and GS groups. When compared with the GS group, women who underwent RRSO had poorer sexual functioning and more endocrine symptoms such as vaginal dryness, dyspareunia, and hot flashes. Women who underwent RRSO experienced lower levels of breast and ovarian cancer distress and had a more favorable perception of cancer risk.
Women (N = 182) at risk of hereditary breast and ovarian cancer referred for genetic counseling were surveyed concerning their satisfaction with their choice of either RRSO or periodic screening (PS) (biannual pelvic examination with TVUS and CA-125 determination) to manage their ovarian cancer risk.[274] Overall satisfaction with both options was extremely high, but highest among those who chose RRSO over PS. There were no other demographic or clinical factors that distinguished satisfaction level. There was higher decisional ambivalence among those who chose PS.
A retrospective study assessed 98 carriers of BRCA pathogenic variants who underwent RRSO about their preoperative counseling regarding symptoms to expect after surgery.[275] The mean age at RRSO was 45.5 years (range, 32–63 y). Eighty-five percent pursued RRSO after learning that they harbored a BRCA pathogenic variant, and 48.0% were premenopausal at the time of surgery. Participants reported ‘‘frequent’’ or ‘‘very frequent’’ postsurgical symptoms of vaginal dryness (52.1%), changes in interest in sex (50.0%), sleep disturbances (46.7%), changes in sex life (43.9%), and hot flashes (42.9%). Only vaginal dryness and hot flashes were commonly recalled to have been addressed preoperatively. While 96% would have the surgery again, participants reported that the discussion of the impact of surgery on their sex life (59.2%), risk of coronary heart disease (57.1%), and the availability of sex counseling (57.1%) would have been helpful.
Behavioral Outcomes
A study [276] of screening behaviors of 216 self-referred, high-risk (>10% risk of carrying a BRCA1/BRCA2 pathogenic variant) women who are members of hereditary breast cancer families found a range of screening practices. Even the presence of known pathogenic variants 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 ultrasound or TVUS. Further analysis of this study population [276] looking specifically at 107 women with informative BRCA test results found good use of breast cancer screening, though the uptake rate in younger carriers is lower. The reason for the lower uptake rate was not explored in this study.[277] One survey of screening behaviors among women at increased risk of breast/ovarian cancer identified physician recommendations as a significant factor in adherence to screening.[278]
While motivations cited for pursuing genetic testing often include the expectation that carriers of pathogenic variants will be more compliant with breast and/or ovarian screening recommendations,[276,279-281] limited data exist about whether 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. The impact of cancer genetic counseling on screening behaviors was assessed in a U.K. study of 293 women followed for 12 months postcounseling at four cancer genetics clinics.[282] BSE, CBE, and mammography were significantly increased after counseling; however, gaps in adherence to recommendations were noted: 38% of women aged 35 to 49 years had not had a mammogram by 12 months postcounseling. BSE was not done by most women at the recommended time and frequency.
This is a critical issue not only for women testing positive, but also for adherence to screening for those testing negative and 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 after 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 BSE, for which compliance is negatively associated with procedure-specific anxiety.[73] 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 before 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, BSE, 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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Changes to This Summary (03/21/2019)
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Updated statistics with estimated new breast, ovarian, and endometrial cancer cases and deaths for 2019 (cited American Cancer Society as reference 1).
Updated National Comprehensive Cancer Network (NCCN) as reference 149.
Added this new section.
Updated NCCN as reference 95.
The Lynch syndrome subsection was extensively revised.
Added text to state that the lifetime risk of endometrial cancer is estimated to be between 19% and 28%, depending on the cohort studied, with an increased risk of premenopausal onset (cited Pilarski et al. as reference 376). Because of the low prevalence of PTENpathogenic variants in the population, the proportion of endometrial cancer attributable to Cowden syndrome is small. There are no data that link PTEN pathogenic variants to an increased risk of ovarian cancer.
Updated NCCN as reference 33.
Added text to state that the Prospective Outcomes in Sporadic versus Hereditary breast cancer study recruited 2,733 women, 12% of whom had a BRCA1/BRCA2 pathogenic variant. Carriers showed no significant difference in outcome from noncarriers (cited Copson et al. as reference 266). However, the cohort of patients with triple-negative breast cancer had a better overall survival than noncarriers at 2 years, but not a statistically significant difference at 5 and 10 years.
Updated Table 13: Available Clinical Practice Guidelines for Hereditary Breast and Ovarian Cancer to include the European Society of Medical Oncology as a resource.
This summary is written and maintained by the PDQ Cancer Genetics Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.
About This PDQ Summary
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the genetics of breast and gynecologic cancers. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Cancer Genetics Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
- be discussed at a meeting,
- be cited with text, or
- replace or update an existing article that is already cited.
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewers for Genetics of Breast and Gynecologic Cancers are:
- Doreen Agnese, MD (The Ohio State University)
- Kathleen A. Calzone, PhD, RN, AGN-BC, FAAN (National Cancer Institute)
- Ilana Cass, MD (Cedars-Sinai Medical Center)
- Lee-may Chen, MD (UCSF Helen Diller Family Comprehensive Cancer Center)
- Mary B. Daly, MD, PhD (Fox Chase Cancer Center)
- Jennifer K. Litton, MD (University of Texas, M.D. Anderson Cancer Center)
- Suzanne M. O'Neill, MS, PhD, CGC
- Tuya Pal, MD, FACMG, FCCMG (Vanderbilt-Ingram Cancer Center)
- Beth N. Peshkin, MS, CGC (Lombardi Comprehensive Cancer Center at Georgetown University Medical Center)
- Susan K. Peterson, PhD, MPH (University of Texas, M.D. Anderson Cancer Center)
- Mary Beth Terry, PhD (Columbia University Mailman School of Public Health)
- Susan T. Vadaparampil, PhD, MPH (H. Lee Moffitt Cancer Center & Research Institute)
- Catharine Wang, PhD, MSc (Boston University School of Public Health)
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PDQ® Cancer Genetics Editorial Board. PDQ Genetics of Breast and Gynecologic Cancers. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/breast/hp/breast-ovarian-genetics-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389210]
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