Psychiatric Annals


Dealing with Uncertainty in Genetic Testing

Veronica Slootsky, MD


Testing for BRCA1 and BRAC2 deleterious mutations, and the subsequent decisions about prophylactic surgery, have an important effect on the psychological well-being of an individual. Studies have found that over time, the psychological well-being of at-risk women who test positive returns to baseline, and women at high risk who are tested and are found to be negative for the mutations have an improvement in their psychological state. However, at-risk women who decline testing were noted to have an increase in depression. Family dynamics play a role in each individual’s experience with BRCA testing. For women who test positive for BRCA mutations, choosing whether to have a prophylactic mastectomy and bilateral salpingo-oophorectomy are decisions that may affect self-image and psychological well-being. Multiple sources for psychological support are available for women who undergo the process of testing and decision-making about prophylactic treatment options.

[Psychiatr Ann. 2014; 44(7):329–333.]


Testing for BRCA1 and BRAC2 deleterious mutations, and the subsequent decisions about prophylactic surgery, have an important effect on the psychological well-being of an individual. Studies have found that over time, the psychological well-being of at-risk women who test positive returns to baseline, and women at high risk who are tested and are found to be negative for the mutations have an improvement in their psychological state. However, at-risk women who decline testing were noted to have an increase in depression. Family dynamics play a role in each individual’s experience with BRCA testing. For women who test positive for BRCA mutations, choosing whether to have a prophylactic mastectomy and bilateral salpingo-oophorectomy are decisions that may affect self-image and psychological well-being. Multiple sources for psychological support are available for women who undergo the process of testing and decision-making about prophylactic treatment options.

[Psychiatr Ann. 2014; 44(7):329–333.]

Recent media coverage about testing for deleterious BRCA1 and BRCA2 gene mutations as a means of identifying risk factors for some forms of hereditary cancers have led to an increasing number of requests for testing and information about prevention options for women who carry the mutations. As such, it is timely to examine the psychological impact of choosing whether to be tested for the genes and of being a carrier of the BRCA1 or BRCA2 gene mutations. These gene mutations have been shown to confer a lifetime risk of up to 85% for breast cancer and up to 60% for ovarian cancer in female carriers.1 Female carriers also have an increased risk for premenopausal disease and for bilateral breast cancer.1 Male carriers have an increased risk of prostate cancer, and both genders may have an increased risk for bowel and pancreatic cancer.1

Genetic testing for these genes is available to those who have a strong family history of these cancers or have themselves been diagnosed with these diseases. Genetic testing in a given family usually begins when a woman is diagnosed with breast or ovarian cancer and obtains testing. If she tests positive for a deleterious mutation, other family members are subsequently tested. Testing positive can allow female carriers to take appropriate steps in preventing or reducing the risks of hereditary cancer, whereas testing negative can relieve individuals of psychological distress. Women who test positive may choose to undergo either frequent surveillance or prophylactic surgery, depending on individual factors.

It is important to note that many forms of heritable cancer do not yet have an identifiable mutation, and a negative BRCA test does not confer protection against heritable breast or ovarian cancer. Additionally, some BRCA1 and BRCA2 genetic tests are inconclusive, meaning that although a deleterious mutation in the BRCA1 and BRCA2 genes was not detected, a change in one of the genes of undetermined significance was detected.

As a result, there are concerns that testing positive for a deleterious mutation can have an adverse effect on the psychological well-being of a carrier, and also open the possibility for distress due to insurance discrimination and social stigmatization. Prophylactic mastectomy may reduce the risk of breast cancer by 90%, but may lead to body image issues. Discordant test results among relatives may result in some relatives experiencing a form of survivor guilt, whereas others may feel isolated in their experience if other family members test negative. Additionally, a positive test means that the carrier has a 50% chance of passing the mutation to his or her children, which may cause further psychological distress. Reproductive medicine techniques to preserve fertility and to prevent offspring from inheriting the mutated gene are a possibility, but may not be accessible to all patients because these procedures are not necessarily covered by insurance under all carriers.

Psychological Effects of Genetic Testing

Studies have shown that negative testing significantly decreases cancer-related worry, whereas positive testing may initially increase worry. However, anxiety following a positive test appears to return to pre-testing level over time. Watson and colleagues1 conducted a multicenter study in the United Kingdom on the effect of testing for BRCA1 and BRCA2. They found that female carriers benefitted psychologically from the testing, with decreased cancer-related worry at 1-, 4-, and 12-month follow-up marks. Female carriers who were younger than 50 years of age showed an increase in cancer-related worry at 1 month post-testing, but that worry returned to pre-testing levels 12 months later.

Lodder and colleagues2 also conducted a study on women who were being tested for BRCA mutations, and they found that pre-test distress, compounded by a positive result, was significantly associated with general and cancer-related distress after testing. Interestingly, the study also found that women who test negative but have a sister who was recently diagnosed as having the deleterious mutation were at higher risk for depression than other non-carriers despite their negative test results. This finding is likely due to the fact that their sisters were found to be at a significantly increased risk for cancer.2 This may be related to a feeling of survivor guilt.

An important group to consider is those who decline genetic testing despite having a high risk of carrying the mutations. Lerman and colleagues3 conducted a prospective cohort study on 327 individuals who were members of BRCA1- and BRCA2-linked families. Depression rates in those who declined to be tested increased from 26% at baseline to 47% at a 1-month follow-up. However, the depression rate for those who chose to be tested and were negative decreased, and the depression rate for those who tested positive showed no change. The differences in depression were still noted at a 6-month follow-up. Among those individuals in the study who had high cancer-related stress symptoms during a pre-counseling session and also declined testing, there was an eight-fold risk of depression compared with non-carriers. Those who were carriers had a higher risk of depression than non-carriers, but no increased risk overall.3 Therefore, it may be important to recommend testing to individuals who are members of families linked to BRCA mutations in order to reduce the overall risk of depression.

van Roosmalen and colleagues4 found that women who had been diagnosed with breast or ovarian cancer at the time that they were diagnosed with the BRCA mutations had a comparatively increased rate of anxiety and cancer-related distress compared with women who were BRCA positive but did not have a cancer diagnosis. Additionally, women who were diagnosed with cancer within a year prior to testing positive for BRCA mutations were at the highest risk for increased distress. Thus, women who are BRCA positive and also had been diagnosed with cancer are most likely at higher risk for distress and should be considered for referral to counseling for psychological support.4

A study by van Oostrom and colleagues5 found that in one cohort of 65 women followed for 5 years who were tested for BRCA, women who were carriers and non-carriers did not differ significantly on distress measures. Predictors of distress for women who tested positive for BRCA included high pre-test anxiety, having young children, having lost a close relative to breast or ovarian cancer, less open communication within the family about test results, and doubting the test’s validity.5 Women with children may have been concerned about the possibility of not being able to care for them in the event of a cancer diagnosis, and also the potential carrier status of their children. They may have had doubts about how to discuss these issues with their children. Non-carriers who doubted the validity of the genetic test remained more distressed than other non-carriers who did not. These women may have come from families with a strong history of breast or ovarian cancer, and may have difficulty adjusting to a view of not having increased cancer risk. Additionally, both positive and negative changes in relationships among family members were associated with increased distress, but it is not clear how family dynamics were affected by test results.5 It is possible that differing results among family members at increased risk may lead to changes in relationships, leading to issues similar to survivor guilt.

Psychological Impact of Surveillance Versus Prophylactic Surgery

Screening for breast cancer usually involves clinical breast exams as well as imaging. Usually, mammography and breast magnetic resonance imaging are recommended, alternating every 6 months, in addition to biannual exams. Screening for ovarian cancer is of more limited utility, as tests typically only detect advanced disease. Screening for ovarian cancer involves annual pelvic exams, ultrasounds, and a blood test for CA-125 (a marker for ovarian cancer). Women may also choose to undergo chemoprevention against breast cancer with a medication such as tamoxifen (an antagonist of estrogen in breast tissue).

For a BRCA-positive woman, the choice of whether to undergo prophylactic surgery or continued surveillance is a highly personal decision that is dependent on many factors. These factors may include personal cancer history, age, other risk factors for breast or ovarian cancer, plans for childbearing, whether the woman witnessed cancer in close relatives, the culture of medicine in the country where they live, and other factors unique to each individual. Many women who choose to undergo prophylactic mastectomy obtain reconstructive surgery. Of note, as women who carry the mutation age, their relative risk of breast cancer slowly approaches that of their non-carrier peers, due to the increased overall risk of breast cancer in aging women. Thus, some women who are diagnosed as BRCA-positive carriers late in life choose to undergo periodic surveillance for breast cancer rather than prophylactic mastectomy. In one study, women who had at least one younger child and a first-degree relative with breast or ovarian cancer had decreased time to prophylactic mastectomy.6

Because surveillance options are more limited and not as effective for detecting ovarian cancer, women who are BRCA positive and have completed childbearing are typically advised to undergo bilateral salpingo-oophorectomy. If these women are premenopausal at the time of this surgery, they enter menopause prematurely due to the removal of the ovaries. This change has implications for other health factors, including bone density, sexual health, and mental health.

Surveillance for cancer, although an acceptable option for many women, may lead to increased anxiety during the time of testing and concerns about one’s future well-being. Due to the high risk of cancer, many women opt for prophylactic surgery. Although the recommendation for bilateral salpingo-oophorectomy is more uniform, the recommendation for prophylactic mastectomy is more variable. In the long-term study by van Oostrom and colleagues5 noted previously, most women who were positive underwent at least one form of prophylactic surgery (21 of 23). These women were generally satisfied with the results of the surgery and had a diminished fear of developing cancer. However, women who underwent the surgery had a less favorable body image than non-carriers, and 70% reported changes in sexual function.5 Women who chose to undergo prophylactic mastectomy and were single at the time of surgery were noted to be “very reluctant” to start a new relationship after the procedure.5 It was also noted that a “considerable” number of these long-term gene carriers obtained psychological and psychopharmacological support from the medical system.5 Nevertheless, the reported changes in sexual function were “not a problem” for most of the women, and they noted that it was preferable to dying from cancer at a young age.5 The minimization of the impact of the procedures on sexual functioning was seen by the researchers as an attempt to minimize cognitive dissonance. Given these findings, it is important to explore how women view their sexual identity prior to surgery and to offer assistance through therapy to those who may be affected. Single women may be at risk for problems with body image that can lead to reluctance to seek out romantic relationships, so these concerns should be addressed.

Options for Psychological Support

There are many potential sources of psychological support for women diagnosed with BRCA mutations. A genetic counselor may be the first and only professional a woman may encounter during genetic testing. Getting the results can take 1 month or more; thus, it is crucial that the counselor be trained in identifying and assisting with psychological distress. The individual who is being tested, or has been given the results of the test, may need to be referred for psychological counseling if distressed. Many options are available, ranging from individual psychotherapy to group therapy. It is also important to bear in mind that because these genes are heritable, family dynamics can play a role in the care of high-risk individuals. Decisions about testing and prevention may be influenced by the decisions of others within the family unit.7 Many women have complex relationships with family members who have or have not chosen to be tested themselves. The skilled genetic counselor, psychotherapist, and group leader will be mindful of these relationships, as well as relationships to family members who have been previously affected by cancer.

In addition to screening for anxiety and depression, clinicians should consider screening high-risk individuals for posttraumatic stress disorder (PTSD). Those who have had cancer or who have witnessed cancer in a close relative meet the criteria for witnessing a life-threatening event and may experience symptoms of PTSD. One study of 84 women at risk for hereditary cancer who previously had cancer or witnessed cancer progression in a relative found that 17% had PTSD.8 One fourth of this group also met criteria for generalized anxiety disorder, dysthymia, or major depressive disorder, indicating some comorbidity.8 The same study found low rates of PTSD related to undergoing genetic testing. However, BRCA carriers were disproportionately represented in the group of women who had PTSD due to personal cancer history or cancer in a relative.8 Therefore, it is particularly important to screen for PTSD symptoms in BRCA carriers who have a personal history of cancer or who have witnessed cancer in a close relative.

One population for whom this is especially relevant is the Ashkenazi Jews. BRCA mutations are more common among Ashkenazi Jews (1 in 40 versus 1 in 500 for the general U.S. population), and an online support group called Sharsheret exists for these individuals. Many face similar culturally specific norms regarding marriage, fertility, and spiritual approaches to cancer and turn to this online community for support. There are also groups of “pre-vivors,” consisting of individuals who carry the deleterious mutation, who meet and discuss their experiences together. One study followed 70 carrier women who participated in a 6-month, 12-session expressive-supportive group therapy intervention. It was found that cancer-related worry, anxiety, and depression decreased significantly in these women. For many participants, it was helpful to discuss the difficult decisions one must face as a mutation carrier, as well as life with the high likelihood of cancer. These women also reported decreased anxiety about screenings. Grief reactions in women who tested positive less than 1 year before the intervention noted that their grief improved; however, this was not the case for women who were more than 1 year out from their positive test. This finding may be due to the initial feeling of loss experienced by individuals after a positive test result and underscores the particular importance of referring newly diagnosed carriers to a support group. Also, a significant number of women made decisions about prophylactic surgery during and after the intervention. Knowledge and surveillance levels were unaffected by the intervention, possibly due to high knowledge levels and surveillance behavior at baseline.9


Deleterious BRCA1 and BRCA2 mutations are associated with a significant increase in breast and ovarian cancer among women and a noteworthy increase in prostate and breast cancer among men. Both genders may also have a slightly increased risk of pancreatic and bowel cancer. Currently, genetic testing is available to screen for these mutations and would be important for members of families with breast and ovarian cancer burden. Studies have indicated that genetic testing relieves psychological distress among those who are found to be negative for the deleterious mutations. Additionally, positive test results do not appear to significantly increase long-term psychological distress among carriers, although an increase may occur in the short-term. In fact, high-risk individuals who refuse testing appear to be at greater risk for depression. For those who do test positive for the mutation, it is important for them to be screened for PTSD related to personal history of cancer or to witnessing cancer in a relative. Women who test positive face complicated decisions about prevention, which may include screening, chemoprevention, and prophylactic surgery. Those who do undergo surgery may be at risk for developing body image issues and sexual dysfunction, and may benefit from group or individual therapy to address their concerns. Support groups may be beneficial in reducing anxiety for carriers and in facilitating the decision-making process about prevention strategies.


  1. Watson M, Foster C, Eeles R, et al. Psychosocial impact of breast/ovarian (BRCA1/2) cancer-predictive genetic testing in a UK multi-centre clinical cohort. Br J Cancer. 2004;91(10):1787–1794. doi:10.1038/sj.bjc.6602207 [CrossRef]
  2. Lodder L, Frets PG, Trijsburg RW, et al. Psychological impact of receiving a BRCA1/BRCA2 test result. Am J Med Genet. 2001;98(1):15–24. doi:10.1002/1096-8628(20010101)98:1<15::AID-AJMG1014>3.0.CO;2-0 [CrossRef]
  3. Lerman C, Hughes C, Lemon SJ, et al. What you don’t know can hurt you: adverse psychologic effects in members of BRCA1-linked and BRCA2-linked families who decline genetic testing. J Clin Oncol. 1998;16(5):1650–1654.
  4. van Roosmalen MS, Stalmeier PF, Verhoef LC, et al. Impact of BRCA1/2 testing and disclosure of a positive test result on women affected and unaffected with breast or ovarian cancer. Am J Med Genet A. 2004;124A(4):346–355. doi:10.1002/ajmg.a.20374 [CrossRef]
  5. van Oostrom I, Meijers-Heijboer H, Lodder LN, et al. Long-term psychological impact of carrying a BRCA1/2 mutation and prophylactic surgery: a 5-year follow-up study. J Clin Oncol. 2003;21(20):3867–3874. doi:10.1200/JCO.2003.10.100 [CrossRef]
  6. Julian-Reynier C, Bouhnik AD, Mouret-Fourme E, et al. Time to prophylactic surgery in BRCA1/2 carriers depends on psychological and other characteristics. Genet Med. 2010;12(12):801–807. doi:10.1097/GIM.0b013e3181f48d1c [CrossRef]
  7. DudokdeWit AC, Tibben A, Frets PG, et al. BRCA1 in the family: a case description of the psychological implications. Am J Med Genet. 1997;71(1):63–71. doi:10.1002/(SICI)1096-8628(19970711)71:1<63::AID-AJMG12>3.0.CO;2-T [CrossRef]
  8. Hamann HA, Somers TJ, Smith AW, Inslicht SS, Baum A. Posttraumatic stress associated with cancer history and BRCA1/2 genetic testing. Psychosom Med. 2005;67(5):766–772. doi:10.1097/01.psy.0000181273.74398.d7 [CrossRef]
  9. Esplen MJ, Hunter J, Leszcz M, et al. A multicenter study of supportive-expressive group therapy for women with BRCA1/BRCA2 mutations. Cancer. 2004;101(10):2327–2340. doi:10.1002/cncr.20661 [CrossRef]

Veronica Slootsky, MD, is Resident Physician, The George Washington University, Department of Psychiatry and Behavioral Sciences.

Address correspondence to Lorenzo Norris, MD, Department of Psychiatry and Behavioral Sciences, 2120 L Street, NW, Suite 600, Washington, DC 20037; email:

Disclosure: Dr. Slootsky has no relevant financial relationships to disclose.


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