APPENDIX IV: PSYCHOLOGICAL IMPACT OF MUTATION TESTING

Beth A. Fine, MS, CGC

Psychological issues raised by the availability of susceptibility testing for BRCA1/BRCA2 mutations arise from the ramifications, both positive and negative, of an individual learning that he or she has an increased risk of developing cancer. Many of these issues have been studied prior to the availability of DNA-based testing in the context of risk perception among relatives of women with breast cancer and adherence to surveillance recommendations in response to these risk perceptions. A central theme of women living "at risk" is the psychological impact of living with uncertainty. In addition, the search for the etiology of breast cancer has held hope for better prevention, treatments and cure.

Those living with cancer or members of "cancer families" are among those who might benefit from genetic susceptibility testing. For example, unaffected individuals with a mutation could participate in more frequent and extensive surveillance with a potentially increased likelihood of early detection, less radical treatment and ultimately, better outcomes. Individuals identified as mutation carriers may opt for preventive measures such as prophylactic mastectomy and oophorectomy. Chemoprevention with medications such as tamoxifen and other preventive agents yet to be identified could be considered and offered to at-risk patients once efficacy has been established. Some individuals may modify their lifestyles, and make employment and/or reproductive decisions based on genetic test results. Also, susceptibility testing may clarify risks for patients who often perceive the risk of developing cancer to be higher than it is, thus reducing psychological distress for the individual and her family.

In the process of deciding whether or not to utilize a cancer susceptibility test, the psychological consequences of testing and not testing must be considered. While the majority of testing for unaffected individuals is conducted after a mutation is identified in an affected individual, the consequences for the affected family member may be different than for the unaffected relative. When an affected individual learns that he or she has a mutation, there may be relief from the burden of living with uncertainty. The empowerment of this knowledge may be profound, i.e., the answer to the question, "Why me?" has been found. This patient can then choose preventive surgical strategies and appropriate surveillance in light of the possibility of recurrence. In addition, she has the responsibility of sharing the test results with family members who are at risk.

Possible psychological responses and related issues to consider when a mutation is detected in an unaffected individual (positive result) include anxiety engendered by confirmation of increased risk and need for increased surveillance; guilt about passing the susceptibility on to future generations; and concerns about privacy of genetic information and the risk of insurance and employment discrimination. The individual may be relieved from the resolution of uncertainty, but also needs to adjust to his/her new risk status, and to be aware of the medical justification for increased surveillance and subsequent reassurance from these measures. There may be opportunities to participate in clinical trials which may lead to the satisfaction associated with contributing to research. In addition, the individual must recognize and explore the impact of this information on relationships. There could be psychological benefits associated with informing family members of their risk status and test availability (such as sharing of anxiety, alleviation of guilt, etc.), leading to deeper and improved relationships. However, concerns about family dynamics with regard to testing, caregiving and support may arise as well. Anticipatory loss surrounding the fear of cancer diagnosis, compromised health and ability, and death must be addressed.

If an individual obtains a negative test result when a specific mutation has been detected in an affected family member, he or she may experience survivor guilt, wondering why he or she was spared the fate of the affected relative. There may be relief of the anxiety and psychological distress associated with perceived and expected high-risk status. This individual can now follow surveillance measures recommended for the general population which may constitute a change in psychological mindset and behavior. Finally, the patient will experience concern about the affected and mutation-positive relatives as well as about his or her potential role as caregiver.

When an unaffected individual tests negative without a known mutation in the family, she or he must face the reality of continued uncertainty and the loss (at least until future research changes the situation) of the possibility of confirming the perception of high-risk status. In this situation, disappointment may occur because the outcome of testing provides no useful information.

Croyle and colleagues (1997) reported that, among women with positive test results in a large breast cancer family, those who had not had cancer or preventive surgery had more psychological distress than those who had had cancer or prophylactic surgery, presumably because they had anticipated the positive result for themselves and were psychologically adjusted to their perceived high-risk. It is important to consider the context when evaluating data from studies conducted within research settings. While many of the psychosocial and coping issues apply to all individuals at risk who might consider testing, individuals seeking genetic counseling and testing for cancer susceptibility in a clinical setting may differ in numerous ways. First, individuals participating in research protocols are motivated in a different way than those seeking information for themselves. Second, demographic variables such as religion, culture, economic status and education level may affect the psychological profile in a way that is not generalizable. Third, individuals in families where cancer is part of their lore and culture are expected to respond differently than individuals at risk whose families have had less experience with the disease.

Pre-Test Education and Counseling

The health care provider must work with the at-risk client using the techniques of "anticipatory guidance" to help the client consider the following issues as part of the decision-making process:

• Do I want to know more about my risk of developing breast/ovarian cancer?

• If so, how will my learning that I have (or do not have) a mutation in my BRCA1 or BRCA2 gene affect me?

• If a mutation is detected, how will I cope with knowing that I have an increased lifetime risk of developing breast/ovarian cancer?

• Will I change my surveillance practices if I learn that I have one of these mutations?

• Will I consider prophylactic surgery, knowing that complete prevention is not possible?

• If I am positive for a mutation, how do I feel about sharing this information with
  family members who may also be at risk?

  LI>If a mutation in BRCA1 or BRCA2 is not identified in me or in my numerous affected relatives, how will I feel about having no more definitive risk information than I had before?

• What will it mean for me to live with this uncertainty?

• What plans will I make in light of a negative/positive test result?

• How will taking this test affect me, my immediate family, and my extended family?

• Do I want to pursue this testing? Now? Perhaps in the future?

Genetic Counseling for Mutation Testing/Informed Consent

A standardized "informed consent" document should be reviewed, point by point, with every client prior to testing. The client's signature on the document, while important from the legal standpoint, should be considered as the culmination of the informed consent process. Many of the points iterated in the pre-test education section in the Guidelines should be reviewed with the client as part of this process. In addition, the health care provider should discuss the following issues with the client:

• If I am unaffected with cancer, I will need to request that an affected family member agree to provide a sample of blood for initial testing. In the event that a mutation is detected, I, and other relatives, will need to know the results of our affected family member's test. Is this possible? What effect will this have on our family relationships? Am I able to approach one or more of my affected relatives?

• Can I comfortably discuss confidentiality with my family members?

• If I am already affected with cancer, a positive result means that I have an increased chance of cancer recurrence. How will I deal with this outcome?

• If I am found to have a mutation, each of my children has a 50% risk of having a mutation as well. How will I deal with this outcome? If my children are under 18 years of age and thus ineligible for testing, can I deal with living with this uncertainty?

• If I am unaffected with cancer, a positive result will clarify my increased risk. I will have to face this risk and will need to work with my doctors to develop an appropriate surveillance and prevention strategy. Will I find this information helpful?

• If I am found to have one of these mutations, I will be asked to notify family members at risk about the availability of genetic counseling and testing. How will I cope with this responsiblity? Can I cope with potential negative reactions?

• Can I comfortably share my results with my physicians and/or my insurance company?

• If I receive negative results and there is a known mutation in my family, my risk is the same as that of the general population. How would I feel about that?

• How will either outcome of this test change the way I think and feel about myself? About my family? About my past and future?

Post-Test Counseling/Results Disclosure and Recommendations

When reviewing recommendations for cancer surveillance after positive or negative results, possible psychological sequelae should be discussed.

• How am I going to deal with the psychological and emotional implications of this information? Do I have an adequate support system in place? Should I seek additional support from professionals, support groups, or other sources?

• Am I prepared for the reactions of family members? I, and my family members, may feel a sense of anticipatory loss since the risk of cancer is so great. Am I able to cope with these feelings that are similar to those faced when a diagnosis of cancer is made?

• Can I seek out preventive/surveillance measures in my community and integrate them into my day-to-day life?

• How do I feel about prophylactic mastectomy/oophorectomy as options? Can I cope with the uncertainty that would remain after such a procedure? How would my husband/significant other feel about such surgery?

• Now that I know about this genetic predisposition, how will my self-image change? How will others' perceptions of me change?

• If I am found not to have the mutation segregating in my family, will I experience and can I cope with the sense of survivor guilt I might feel?

• With whom can I share this information?

• How might I change my lifestyle?

• How will my children feel? Will they want this information and/or testing? When?

References:

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