Many of the psychosocial outcome studies involve specialized, highly selected research populations, some of which were utilized to map and clone BRCA1 and BRCA2. One such example is K2082, an extensively studied kindred of more than 800 members of a Utah Mormon family in which a BRCA1 mutation accounts for the observed increased rates of breast and ovarian cancer. A study of the understanding that members of this kindred have about breast/ovarian cancer genetics found that, even in breast cancer research populations, there was incomplete knowledge about associated risks of colon and prostate cancer, the existence of options for risk-reducing mastectomy (RRM) and risk-reducing salpingo-oophorectomy (RRSO), and the complexity of existing psychosocial risks. 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. These prospective studies, however, were characterized by a heterogeneity of measures of cancer-specific worry and inconsistent findings in effects of change from baseline.
It is not yet clearly established to what extent findings derived from special research populations, at least some of which have long awaited genetic testing for breast/ovarian cancer risk, are generalizable to other populations. For example, there are data to suggest that the BRCA1/BRCA2penetrance estimates derived from these dramatically affected families are substantial overestimates and do not apply to most families presenting for counseling and possible testing.
Emotional Outcomes of Individuals
The few studies conducted to date of psychological outcomes associated with genetic testing for mutations in breast/ovarian cancer predisposition genes have shown low levels of distress among those found to be carriers and even lower levels among noncarriers.[63,88,89,90,91] A systematic review found that the studies assessing measures of distress (9 of 11 studies) found no change, or a decrease, in those parameters (including anxiety, depression, general distress, and situation distress) in people who had undergone testing at assessments done at 1 month or less, and 3 to 6 months later. One follow-up study from the United Kingdom measured levels of cancer-related worry, general mental health, risk perception, intrusive or avoidant thoughts, and risk-management behaviors at baseline and 1, 4, and 12 months after results were provided. This study included 202 unaffected women and 59 unaffected men, of whom 91 tested positive and 170 tested negative. Results showed that while female noncarriers had significant (P < .001) reductions in cancer-related worry, female carriers younger than 50 years had an increase in cancer-related worry 1 month posttesting. These levels returned to baseline by 12 months but remained higher than noncarrier levels throughout the 12-month period. Female carriers engaged in more posttest screening than noncarriers (92% vs. 30%) within 12 months of test results disclosure. Thirty carriers had RRM and/or RRSO within the same time period. A slightly smaller subset of this cohort was assessed again for cancer-related worry, general mental health and risk-management behaviors 3 years following genetic test result disclosure. One hundred fifty-four women and 39 males, including 71 carriers and 122 noncarriers, returned the questionnaire. The level of distress and cancer worry was similar between carriers and noncarriers. Female carriers had higher distress levels at 3 years versus 1 year postdisclosure, but their level of cancer worry decreased significantly over the same time period. In female noncarriers, although the level of cancer worry had decreased from baseline to 1 year postdisclosure, these levels returned to baseline by 3 years. The authors did not comment on contextual factors that might influence distress and cancer worry levels. Another study reported that, compared with pretest levels, mean scores on 1-year posttest measures of cancer-specific distress and state-anxiety decreased significantly among noncarriers, while scores on these measures and on a measure of general distress did not change among BRCA1/BRCA2 carriers. One long-term study of 65 female participants explored the psychosocial consequences of carrying a BRCA1/BRCA2 mutation 5 years after genetic testing. Carriers did not differ from noncarriers on several distress measures. Although both groups showed significant increases in depression and anxiety compared with 1 year postdisclosure, these scores remained within normal limits for the general population. Caution is advised by authors of these studies in interpretation of the results as they are all from programs in which results disclosure was preceded by extensive genetic counseling about risks and benefits of BRCA1/BRCA2 testing, psychological assessment, and in some cases exclusion of a few individuals who appeared highly distressed. Intrusive thoughts (measured by the Impact of Event Scale [IES])  about cancer diminished after results disclosure for both mutation-positive and mutation-negative individuals in one Dutch study.