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Across the Spectrum: Case Studies in Genetic Counseling for Breast and Ovarian Cancer Tiffani A. DeMarco,1,2 Beth N. Peshkin,1 and Barbara M. Brogan1
We present three vignettes based on participants counseled as part of a clinical research program. These include a young unaffected woman at risk for a familial mutation, a newly diagnosed breast cancer patient, and a woman with recurrent ovarian cancer. Through the use of detailed vignettes, multifaceted issues that arise in cancer genetic counseling are highlighted. KEY WORDS: BRCA1/2; breast/ovarian cancer; genetic counseling; decision-making.
INTRODUCTION Since the cloning of the BRCA1 and BRCA2 genes in the mid-1990s, genetic counseling and testing have become widely available for individuals at risk for hereditary breast/ovarian cancer. Although several studies have demonstrated that individuals choose to undergo BRCA1/2 testing to obtain information for medical management (Clark et al., 2000), there are no prospective, long-term outcome data about the most effective means to screen for or reduce the cancer risk in carriers. In the absence of such data, guidelines are based primarily on expert clinical opinion (Burke et al., 1997a). In addition, the potential efficacy of certain prevention options, such as prophylactic mastectomy and oophorectomy, has recently been studied (Eisen et al., 2000). Another common reason that individuals seek genetic testing is to obtain information for relatives (Clark et al., 2000). Yet many women, especially those with breast or ovarian cancer, may be unprepared for the medical and emotional 1 Divison
of Cancer Control, Department of Oncology, Georgetown University – Lombardi Cancer Center, Washington, District of Columbia. 2 Correspondence should be directed to Tiffani DeMarco, Georgetown University – Lombardi Cancer Center, 2233 Wisconsin Avenue, NW Suite 317, Washington, District of Columbia, 20007; e-mail:[email protected]. 379 C 2001 National Society of Genetic Counselors, Inc. 1059-7700/01/1000-0379$19.50/1 °
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implications of test results for themselves and their relatives (Dorval et al., 2000). The process of informing family members about cancer risk can be formidable and, for relatives, the subtleties of “true negative results” versus “positive results” may lead to complex emotional responses. There may be psychological benefits associated with BRCA1/2 testing and, for most patients, there do not appear to be significant adverse effects associated with testing (Croyle et al., 1997; Lerman et al., 1996). However, responses to testing represent only one of the many issues faced by those seeking genetic counseling and testing. Psychological and family issues that individuals may have confronted, perhaps many years prior to or concomitant with genetic counseling, may profoundly affect their genetic testing experience. Many of these experiences can be elicited during client centered genetic counseling. Discussion of these factors can help patients make more informed decisions about testing, and prepare them for the potential implications of their decisions. The purpose of this paper is to provide a qualitative overview of some of the complex issues that may arise in genetic counseling for hereditary breast and ovarian cancer. The three case histories presented are drawn from families counseled as part of a clinical research program, and have been modified to protect confidentiality. These cases include a young unaffected woman at risk for a familial mutation, a woman with newly diagnosed breast cancer, and a woman with recurrent disease. YOUNG UNAFFECTED WOMAN Case History Sarah, a 27-year-old graduate student, was referred for genetic counseling following the identification of a BRCA1 mutation in her mother. Her mother had breast cancer at age 35 and was recently diagnosed with ovarian cancer at age 55. Additional family history information is depicted in Fig. 1. Pretest Counseling Summary Sarah was in her second semester of graduate school and had spent the past year at home caring for her mother. She wanted to pursue testing because she felt strongly about gathering as much knowledge as possible about her screening and prevention options. She indicated that although her time at home had brought her closer to her mother, it had also strengthened her desire to prevent herself from ever developing cancer. The session began with a review of the consent process and discussion of confidentiality and insurance discrimination. Sarah was not particularly concerned
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Fig. 1. Young unaffected proband.
about insurance coverage, as health insurance was provided through her school. However, she understood that when she enters the work force, she will not have complete protection against the use of genetic information for employment decisions and as part of an application for new health, life, and/or disability insurance. While she knew this was a potential risk, it was not a deterrent to her decision to undergo genetic testing. The remainder of the session focused on breast and ovarian cancer risks, and screening and prevention options for mutation carriers. Dominant inheritance and the 50% risk for inheriting the mutation that had previously been identified in her mother was discussed. The counselor emphasized that although carrying a mutation in BRCA1 increases the risk of developing cancer, it is not a cancer diagnosis. Sarah said that if she tested positive she would be concerned about her ability to undergo the recommended screening, as her current health insurance would not cover mammograms or ovarian screening for a woman of her age, nor did she feel that she wanted to have a mammogram annually for the rest of her life. She had not established a relationship with her physicians that would allow her to feel comfortable discussing her test results as justification for increased screening. These were issues that Sarah had not contemplated prior to the genetic counseling session. The counselor stressed that the recommendations for mutation carriers were only guidelines, and given Sarah’s young age, she needed to take into
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account the efficacy of screening and prevention methods and her current financial resources. The counselor discussed with Sarah that given that she was graduating next year, if a mutation were identified, she could consider having annual screening (i.e., clinical breast exams and routine gynecologic care) and then pursuing more rigorous screening when she had adequate health insurance. Sarah was aware of prophylactic surgery, but due to her young age this was not a major focus of discussion. She commented that she might decide to have children sooner rather than later if she tested positive, and would consider prophylactic oophorectomy after childbearing was completed. However, she currently felt that she would not consider prophylactic mastectomy. Sarah said that she was not inclined to take medication at this time, but may consider it in the future if she were to test positive. Also, at age 27, Sarah was not eligible for most chemoprevention studies. The role of the birth control pill as a prevention strategy in mutation carriers was also discussed. Sarah had been using oral contraceptives for 5 years and did not plan to discontinue their use. The counselor reviewed data indicating that use of oral contraceptives for more than 6 years in mutation carriers reduces ovarian cancer risk by as much as 60% (Narod et al., 1998). The possible increased risk for breast cancer in young female mutation carriers who use birth control pills was also explained (Ursin et al., 1997). Sarah mentioned that her mother’s recent ovarian cancer diagnosis had made her concerned about the effectiveness of treatment for this cancer. She said that while there may be an increased risk for breast cancer associated with the use of oral contraceptives, she viewed this risk very differently, because her mother, maternal grandmother, and aunt had survived several years following their breast cancer diagnoses. The counselor reminded Sarah that although the counseling had focused mainly on recommendations for individuals who carry a BRCA1 mutation, there was an equal likelihood that she would test negative for the mutation identified in her mother, and the implications of a true negative result were also reviewed. She said that while she wanted to have an optimistic attitude about the outcome of the testing, since the majority of the women in her mother’s family had developed cancer, she would probably be the “next in line.” Sarah was very concerned about her mother’s reaction if she tested positive, particularly feelings of guilt for having passed this mutation on to her daughter. Posttest Counseling Summary Sarah returned for her disclosure session approximately 1 month later, and was elated to learn that she did not carry the BRCA1 mutation identified in her mother. She now felt she could move on with her life at the pace she wanted, whereas previously she felt rushed to accomplish her goals before she developed cancer. Even at the young age of 27, she had convinced herself that a cancer diagnosis was probably inevitable. Because of this, she needed time to convince herself that
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the “cloud of cancer” was no longer hanging over her head. Sarah said she also no longer felt the urgency to have children as soon as possible. She was very thankful she underwent testing and planned to live her life on an unstructured timeline. Commentary Although this case had a “happy ending,” it illustrates several complex issues involved in counseling young unaffected female members of a family with a known deleterious BRCA1 or BRCA2 mutation. One of these major issues involves insurance discrimination. There are very few well-documented cases in which health insurers are using genetic test results in their underwriting decisions (Hall and Rich, 2000). Individuals with presymptomatic genetic conditions (such as unaffected individuals who carry a BRCA1 or BRCA2 mutation) have not reported difficulty in obtaining health insurance (Hall and Rich, 2000). In 1996, a federal law known as HIPAA (Health Insurance Portability and Accountability Act) prevented group health insurers from labeling presymptomatic genetic test results as “a pre-existing condition.” While this and other pending legislation provide protection for patients seeking genetic testing, fear of genetic discrimination still remains one of the primary deterrents to genetic testing (Clark et al., 2000). Although young unaffected patients may have concerns about possible future genetic discrimination, they may also not, at the time of their genetic counseling visit, be properly insured to receive the recommended screening. As demonstrated by Sarah’s situation, young women may be in a transitional period in their lives (such as between jobs, in school) and may therefore not have insurance or have little or no flexibility in their coverage. According to a 1999 survey, 15.5% of the U.S. population is uninsured, and individuals 18–24 years old were more likely than any other age group to lack coverage (a total of 29%) (U.S. Census Bureau, 1999). Not only may these young adults lack health insurance coverage, but they may also be without a physician with whom they have established a comfortable relationship. This lack of rapport may add to a patient’s discomfort in disclosing genetic test results to her provider to justify increased screening. For young women who test positive, counselors may make referrals to health care providers who are knowledgeable about the issues confronting mutation carriers but who may not be covered by a patient’s insurance plan. It is therefore necessary for the genetic counselor to be aware of a patient’s current health insurance situation and discuss alternatives, such as research studies. Even if a young mutation carrier is properly insured and in a position to pay for increased surveillance, she may become frustrated by the lack of concrete recommendations with regard to the age at which she should begin screening. Burke et al. (1997a) recommend clinical breast exams and mammography starting between ages 25 and 35. However, the efficacy of these surveillance options has not been proven in this young population. There has also been concern about the risk of radiation exposure for young women who begin mammography at such an
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early age (Abbott et al., 1998). This issue, coupled with the reduced sensitivity of mammography in younger women (Beam et al., 1996), may cause some patients to question the benefit of learning their genetic test results if there are no proven interventions. Therefore, counseling should include both a discussion of the benefits and limitations of surveillance guidelines. Patients should also understand that any potential risk of screening is outweighed by likely overall benefits (Burke et al., 1997b). A young woman’s decision to seek genetic testing may also be influenced by her family history of cancer (Lerman et al., 1996). As in other instances, an individual’s decision to undergo testing may be significantly affected by the types of cancer in her family, the number of affected relatives, and the ages at which they were diagnosed with cancer. Although this may be true for young women with cancer as well, it may have a greater impact on unaffected women, as their perception of survival may be based solely on their family history. As in Sarah’s case, it was apparent that her personal experience with her mother’s ovarian cancer had greatly affected her views regarding the efficacy of cancer screening and prevention options. The role of the genetic counselor is to facilitate discussion of the possible benefits, risks, and limitations of undergoing genetic testing at a young age. Counselors need to assess how a patient will react to a test result, positive or negative. The ramifications may be even more complex for a young unaffected woman who, depending on her results, may face an increased risk for breast and ovarian cancer over her lifetime or who may be relieved from the burden of her family’s legacy of cancer. YOUNG WOMAN WITH NEWLY DIAGNOSED BREAST CANCER Case History Julie, a 30-year-old Caucasian female newly diagnosed with breast cancer, was referred by her surgeon for genetic counseling and testing because of her young age at diagnosis and her family history of breast cancer (see Fig. 2). She had already undergone an excisional biopsy of a mass in her right breast; however, because she had positive margins, a wide reexcision or a mastectomy was indicated. Julie was scheduled for genetic counseling immediately after her first surgery, and was informed that if she desired testing, results would be available in approximately 3 weeks. Pretest Counseling Summary At Julie’s first counseling visit, only 8 days after she received the diagnosis of breast cancer, she was anxious. She was overwhelmed with the information about
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Fig. 2. Newly diagnosed proband.
treatment options she had gathered. She asked many questions about chemotherapy, radiation therapy, and surgical options. The counselor explained to Julie that the majority of her questions could not be answered until after additional surgery when her physicians would have information about prognostic factors and treatment options. Because Julie required another surgery to treat her breast cancer, she wanted to have as much information as possible to make an informed decision about what procedure to choose. Julie’s personal and family history was suggestive of hereditary breast cancer. Once she understood this, she became more concerned about developing a new primary breast cancer. However, she said that her surgeon felt confident that breast conserving surgery was an appropriate option to treat her current breast cancer. But, at age 30, Julie worried about feeling anxious if she opted
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for breast conserving surgery and close surveillance. Her current breast cancer was not detected by mammography, nor did her physician detect any masses during her breast exam performed just 2 months before Julie discovered the lump herself. She could not imagine hearing the words “You have breast cancer” a second time, and wanted to do everything possible to reduce her risk. For these reasons, Julie felt certain that she would choose bilateral mastectomies if she tested positive for a BRCA1 or BRCA2 mutation. Another focus of the genetic counseling session was a discussion regarding the difference between a cancer recurrence and the risk of developing a new primary breast cancer in the ipsilateral or contralateral breast. The counselor explained that the risks associated with carrying a BRCA1 or BRCA2 mutation are for a new primary breast cancer. It was further explained that the risk for a recurrence was based on prognostic factors that Julie could discuss in greater detail with her oncologist. It was discussed that her genetic test results would not influence recommendations about adjuvant treatment for her current breast cancer. After discussing the risk for developing another new primary breast cancer, the counselor also talked with Julie about ovarian cancer risks associated with a BRCA1 or BRCA2 mutation (Frank et al., 1998). Because she was still reeling from her new breast cancer diagnosis, she could not thoroughly process information about other cancer risks at the time of her counseling session. Nevertheless, Julie decided to undergo genetic testing because she felt that it would provide her with another piece of information to factor into her current decision-making process. She also felt that finding out that she had an inherited susceptibility to breast cancer would answer her question as to why she and her family members had developed breast cancer at young ages.
Posttest Counseling Summary The counselor met again with Julie 3 weeks later and informed her that she carried a deleterious mutation in BRCA1. Even though she was certain during her pre-counseling session that she would choose bilateral mastectomies if a mutation was identified, she was not as confident after hearing her results. After several conversations with the counselor and her surgeon, Julie decided to undergo breast conserving surgery and 7 weeks of radiation therapy. Julie was satisfied with her decision and would be undergoing close surveillance for breast cancer, consisting of monthly breast self-exam, physician breast exam every 3–6 months, and annual mammograms. Julie planned to consult with a gynecologic oncologist about recommendations for ovarian cancer screening but might consider prophylactic oophorectomy after completing her family. She also informed her sisters about the mutation that had been identified and the options available for genetic counseling and testing.
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Commentary Women with a mutation in BRCA1 or BRCA2 have up to a 65% risk for developing a new primary cancer in their contralateral breast (Ford et al., 1994), and an elevated risk of ipsilateral breast cancer (Turner et al., 1999). Given the increased risks for developing a new primary breast cancer, it is easy to understand why mutation carriers struggle with a surgery decision. In the general population, randomized trials of mastectomy versus breast conserving surgery have demonstrated no difference in long-term survival (Lichter et al., 1992). Therefore, surgical decisions are often made based on surgeon’s recommendations and quality of life issues. Whelan et al. (1999) reported that a “decision board” developed to assist surgeons in presenting information to patients regarding mastectomy and breast conserving surgery facilitated shared decision making between the surgeon and the patient. Similar tools may also be developed to assist mutation carriers with the difficult decisions they encounter at the time of a new breast cancer diagnosis. A decision-aid may be particularly helpful for newly diagnosed mutation carriers because the very high risks for a second breast cancer may influence a patient’s decision about breast conserving surgery. Newly diagnosed patients who are found to have a mutation in BRCA1 or BRCA2 may opt for bilateral mastectomies to reduce their risk of a subsequent breast cancer. They may also be influenced by recent data that indicate that BRCA1/2 mutation carriers who underwent bilateral prophylactic mastectomies reduced their risk for developing breast cancer by 90% (Hartmann et al., 2000). Because of the high risk for contralateral breast cancer in mutation carriers and the efficacy of prophylactic bilateral mastectomies, this surgical choice is a reasonable option for the newly diagnosed patient. However, factors such as the extensive nature of the surgery, recovery time, and possible alternatives for reconstruction also need to be considered. The process of genetic counseling and testing prior to making a surgery decision was still helpful to Julie, even though she did not choose to undergo more extensive breast surgery. BRCA1/2 status may be factored into future surgical decisions. For example, women may choose bilateral mastectomies after having completed cancer treatment. However, drawbacks to delaying bilateral mastectomies include the prior completion of radiation treatments and the need to undergo additional surgical procedures. In general, a nondirective counseling approach facilitates discussion of these issues and assists patients in making a decision about which surgical option is best for them, not the one the counselor might make or believes the patient should make. In addition to addressing surgical options, genetic counseling for newly diagnosed breast cancer patients often involves a complex discussion of the difference between a recurrence of a woman’s current breast cancer and her risk for developing a new primary breast cancer. As illustrated in Julie’s case, her surgeon made it clear that lumpectomy with radiation was a reasonable option for treating her current breast cancer. There are no data at present that indicate that breast conserving
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surgery followed by radiation therapy is contraindicated in BRCA1/2 mutation carriers to treat the cancer they have. For example, Pierce et al. (2000) found that there was no significant difference in local recurrence and/or 5-year survival rate between patients with a BRCA1/2 mutation versus sporadic controls undergoing radiation after breast conservation. While longer follow-up is needed, these data may be helpful when discussing treatment options with newly diagnosed patients. A recent study suggested that use of tamoxifen significantly reduced the risk of contralateral breast cancer in patients with a BRCA1 or BRCA2 alteration (Narod et al., 2000). Although these data are encouraging, use of tamoxifen to treat newly diagnosed breast cancer patients is still a complex issue, particularly for those women whose tumors may be estrogen receptor negative. Overall, it is essential that the newly diagnosed patient comprehends that the results of BRCA1/2 testing are currently not a major factor in determining use of adjuvant treatment and subsequent prognosis. Because newly diagnosed patients are often focused on their impending surgical decision and subsequent treatment, they may not be in a position to assimilate information about future cancer risk, particularly ovarian cancer. The majority of patients affected with breast cancer who seek genetic counseling have already made their surgical decisions and in most cases have completed treatment. Thus, they may be better able to comprehend information about risk for future cancers. Many newly diagnosed patients want only to treat the breast cancer they have and deal with any future cancer risk at a later time. Their primary motivation is to move past the initial shock of a breast cancer diagnosis and get on with their lives. Therefore, it is important for the counselor to strike a balance between addressing the patient’s new breast cancer, their primary concern, and feeling compelled to discuss other cancer risks, which can be addressed after a patient has undergone surgery. While it is apparent that some mutation carriers may struggle with their surgical decision at the time of a new diagnosis, there is no information in the literature about genetic counseling and testing for newly diagnosed breast cancer patients. Therefore, the informational and supportive needs of these patients are not well known or understood. Women newly diagnosed with breast cancer perceive information about the likelihood of cure, the spread of the disease, and treatment options as the most important information needed at the time of diagnosis (Luker et al., 1995). It is important to allow patients the opportunity to express their concerns, so that they can focus on the genetic counseling issues. For this reason, sessions with newly diagnosed breast cancer patients often last 2–3 hours. It is also valuable for the counselor to have some knowledge of clinical oncology and breast cancer treatment options. This helps to build rapport with the patient, assists in identifying pertinent issues, and allows the session to be tailored to meet the needs of the patient. Women newly diagnosed with breast cancer are a challenging group to counsel. Counselors should not assume that all young women with newly diagnosed breast cancer will be interested in having genetic testing in order to make surgery decisions. Patients may opt for genetic testing but proceed with surgery before
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learning the results. Some patients may choose to learn the results prior to making a surgery decision, while others may choose to have genetic testing after they have completed treatment for their breast cancer. RECURRENT/METASTATIC DISEASE Case History Anne, a 51-year-old Caucasian woman with recurrent ovarian cancer, was referred for genetic counseling by her gynecologic/oncologist. In 1996 she had been diagnosed at age 48 with Stage IIIC cystadenocarcinoma for which she underwent debulking surgery followed by chemotherapy. Recently, liver metastases were discovered, for which Anne was participating in a clinical trial of a new chemotherapy regimen. The remainder of her medical history was unremarkable. Family history information is depicted in Fig. 3. Pretest Counseling Summary Anne requested that her genetic counseling appointment occur during one of the weeks when she was not receiving treatment, and that it be limited to an hour due to her fatigue. To accommodate her requests, family and medical history information was obtained through mailed forms and telephone. During the history
Fig. 3. Proband with recurrent ovarian cancer.
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collection, Anne revealed that she had not had a mammogram since her initial diagnosis, and had never had colon screening. During the genetic counseling session Anne appeared haggard and indicated that her main reason for wanting testing was to gain information for her daughters. Anne never directly raised issues about her prognosis, but described her attempts to “tie up things” in her life, which she hoped that the treatment would buy her enough time to accomplish. She requested that her BRCA1/2 results be provided to her over the phone in light of her condition. The pretest genetic counseling session focused on risk assessment and preparing her for the high likelihood that a BRCA1 or BRCA2 mutation would be identified; however, the possibility of a negative result was also explained. Autosomal dominant inheritance was reviewed, and it was emphasized that relatives other than her daughters were at risk, including her son, siblings, and cousins. Previously she had thought that a positive test result would have implications only for her daughters. Cancer risks and management options were discussed primarily as this information would apply to relatives. It was acknowledged that Anne was appropriately concentrating on her current treatment and that medical implications to her would need to be considered in the context of her general health. The recommendations for annual mammograms and colon cancer screening were framed as they might apply to her family members. Anne questioned why her doctors never recommended that she undergo ovarian screening or have her ovaries removed in light of her family history and the information she had just learned about the association of breast and ovarian cancers with BRCA1/2 mutations. The counselor explained that information about hereditary breast/ovarian cancer was still very new and that without documentation of a complete family history, it may be difficult to identify this syndrome, or the possible transmission of risk through the paternal lineage. In addition, screening for ovarian cancer is imperfect (Burke et al., 1997a), and residual cancer risks remain even after prophylactic oophorectomy. Anne’s anger and disappointment at not being advised of her ovarian cancer risk were acknowledged, as was her desire to find a reason why she developed cancer and what she could have done to avoid it. These reactions were somewhat defused by the idea that her family may use information about her test results proactively. Anne discussed how she would communicate information about her test results to her family and how she would cope if any of her children tested positive. She again remarked that her hope was that if she tested positive, the information would be used constructively. She stated that learning such a result would be a “relief” in that she would understand the likely reason why she got cancer, would know that she had some concrete information to share with her relatives, and that there would be no medical implications to her in light of her current condition. She felt the news could not affect her as adversely as having learned that she had metastatic ovarian cancer. In addition, she stated that her family was close knit and very supportive.
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Posttest Counseling Summary Four weeks after the initial genetic counseling session, the genetic counselor called Anne with her results, which revealed that she had a deleterious mutation in BRCA1. Anne had recently returned from a 5-day stay in the hospital after a bout with pneumonia and was still quite weak. Thus, the telephone discussion lasted less than 15 min. Most of the time was spent responding to Anne’s concerns about how her relatives could get information about obtaining genetic counseling. A short summary letter was sent to Anne, primarily reviewing implications to her relatives and logistics of obtaining genetic counseling/testing in their locales. Commentary The optimal approach to genetic counseling about hereditary breast cancer often involves two in-person visits for genetic counseling. Because of the severity of the patient’s illness, the initial session was streamlined by obtaining medical and family history information by phone prior to the visit. This allowed the counselor to focus on family and psychosocial issues during the in-person visit. The chance of finding a BRCA1 or BRCA2 mutation in this family was estimated to be about 90% (Frank et al., 1998). Therefore, it was appropriate to structure much of the discussion around the strong possibility that the patient would test positive, and what the familial implications would be. Although it was not stated by the patient herself, it was clear that her prognosis was poor and that she may not live more than a few months. Thus, to maintain rapport with this patient it would have been inappropriate to discuss in detail the medical implications of a positive test result to the patient herself. For example, Anne was made aware that prophylactic mastectomy is an option for at-risk relatives, but not necessarily for her. In addition, her doctors had recommended that she obtain a mammogram after her initial treatment was completed, but she never followed up. Given her health, neither her doctors nor she was concerned with her breast cancer risk, and no doctor had broached the subject of other screening, such as colon cancer screening. The counselor provided support for her during the session, acknowledged how difficult this time was for her, and assisted Anne in sorting through the impact her testing decision would have on her family. Finally, telephone disclosure of test results was an acceptable alternative in this case as Anne was well prepared for the information and had a good support system in place. Women with ovarian cancer, particularly those with declining health, may experience significant psychological distress (Kornblith et al., 1995). Women in the terminal stages of cancer may also be dealing with their spirituality, family concerns, and physical pain (Greisinger et al., 1997). Clinicians providing genetic counseling must understand the relative significance of the genetic testing experience. Tailoring the genetic counseling sessions, including streamlining the information and considering exceptions to standard protocol procedures, may be
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acceptable and desirable for some patients. However, providers are still obliged to engage in the informed consent process and ensure that patients understand the implications of the information imparted to them. A recent study showed that cancer patients may underestimate their emotional reactions to a positive result (Dorval et al., 2000), thus underscoring the need to provide anticipatory guidance to all individuals, especially cancer patients, at the time of their initial genetic counseling session. Although counseling can never fully prepare people for how they may ultimately react to genetic test results, it will allow them to contemplate the complex issues that are likely to arise. DISCUSSION This paper examined genetic counseling for breast and ovarian cancer susceptibility across a spectrum of patient issues: a healthy unaffected woman at risk for a familial mutation, a newly diagnosed breast cancer patient, and finally a terminally ill patient. Although genetic counseling for these three patients involves addressing the specific needs of these individuals, there are also several common themes. These themes include the uncertainty that patients must face regarding risk assessment, possible cancer risks and the lack of proven screening and prevention options. This complexity underscores the importance of collecting and validating data about probabilities of being a BRCA1/2 carrier, cancer risks associated with mutations in these genes, and the efficacy of screening modalities and prevention options. Obtaining this information will contribute to more informed patient decision making. It is hoped that the cancer risks associated with BRCA1/2 mutations may eventually be individually tailored based on a patient’s ethnic background and the specific mutation identified, along with other genetic and environmental risk modifiers. In addition, long-term outcome data about the efficacy of surveillance, prophylactic surgery, and chemoprevention options in mutation carriers will be beneficial to patients as they strive to make informed decisions about medical management. A second theme involves the disclosure of test results to relatives. A cancer diagnosis, whether a new breast cancer or recurrent ovarian cancer, creates emotional challenges for the patient as well as for family members (Hilton, 1993; Kornblith et al., 1995). As a result, women may not wish to burden their relatives with the complex issues surrounding their genetic test results. However, for some women, information for relatives may be the primary motivator for their seeking testing. Genetic testing is likely to have an impact on all family members, and therefore helping patients develop an appropriate plan to inform their relatives is a vital component of genetic counseling. Finally, it is expected that the sequencing of the human genome will eventually give rise to clinically translatable information through the identification of new genes predisposing to adult onset conditions such as heart disease, diabetes,
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and many forms of cancer (Collins, 1999). Therefore, over the next several years there will be heightened interest in genetic testing for cancer predisposition. The lessons learned from genetic counseling for hereditary breast cancer underscore the importance of comprehensive pre- and posttest counseling and the need to educate and involve a multidisciplinary group of providers to impart such services (McKinnon et al., 1997). It is hoped that as genetic testing becomes more widely available, broader legislation on the state and federal levels will decrease the perceived threat of genetic discrimination, a concern that may be a significant barrier in patient decision making and genetic testing utilization. The counseling issues (see Table I) and themes discussed in this paper are applicable to other genetic conditions. The experience with counseling women at high risk for hereditary breast and ovarian cancer will help refine genetic counseling and follow-up, thus maximizing the potential benefits while minimizing the possible adverse effects of genetic testing. Table I. Medical and Psychosocial Issues Faced by Three Genetic Counseling Patient Populations
Medical issues
Young unaffected female
Young, with newly diagnosed breast cancer
Recurrent cancer/ poor prognosis
Integration of cumulative cancer risk estimates
Surgical and adjuvant treatment decisions
Tailoring medical info and shifting emphasis to patient’s agenda Recognizing prognosis and the implications of testing
Vague screening recommendations
Distinguishing between new primary and recurrence Difficulty assessing Addressing risk of 2nd the positives and cancers—including negatives of hormonal ovarian cancer options Potential problems Time pressure related accessing health care to surgical decision making Short-/long-term decision making Psychosocial issues
Possibility of genetic discrimination Body image Family planning
Distress associated with new diagnosis Sexuality and body image Survival concerns
Impact of family history Family communication of cancer re: diagnosis and genetic test results Assimilation of test result
Family communication Addressing “why” cancer occurred Understanding of how testing fits into patient’s need to “tie-up” issues
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ACKNOWLEDGMENTS The authors thank all of the men and women who participated in our research studies. In addition, we are grateful to Michael Begleiter, MS, Holly Ishmael, MS, Anne O’Connor, RN, MSN, AOCN, and Kenneth Tercyak, PhD, for their review of the manuscript and insightful comments. Also, special thanks to Annalisa DialinoFelix, BS, for preparing the pedigrees, and to Claudine Isaacs, MDCM, Medical Director of our research program. This research was supported by Department of Defense Grant DAMB 1796-C-6069, Grant RO1 HG01846 from the National Human Genome Research Institute, and Grant RO1 CA74861-03 from the National Cancer Institute/National Institutes of Health. (Principal Investigators: Caryn Lerman, PhD, Chanita Hughes, PhD, and Marc Schwartz, PhD). Additional support was provided by institutional funds from the Lombardi Cancer Center. REFERENCES Abbott DW, Freeman ML, Holt JT (1998) Double-strand break repair deficiency and radiation sensitivity in BRCA2 mutant cancer cells. J Natl Cancer Inst 90:978–985. Beam CA, Layde PM, Sullivan DC (1996) Variability in the interpretation of screening mammograms by US radiologists: Findings from a national sample. Arch Intern Med 156:209–213. Burke W, Daly M, Garber J, Botkin J, Kahn MJ, Lynch P, McTiernan A, Offit K, Perlman J, Petersen G, Thomson E, Varricchio C (1997a) Recommendations for follow-up care of individuals with an inherited predisposition to cancer: II. BRCA1 and BRCA2. JAMA 277:997–1003. Burke W, Daly M, Garber J, Botkin J, Kahn MJ, Lynch P, McTiernan A, Offit K, Perlman J, Petersen G, Thomson E, Varricchio C (1997b) Benefits and risks of screening mammography in women with BRCA1 and BRCA2 mutations. JAMA 278:290–291. Clark S, Bluman L, Borstelmann N, Regan K, Winer E, Rimer BK, Skinner CS (2000) Patient motivation, satisfaction, and coping in genetic counseling and testing for BRCA1 and BRCA2. J Genet Counsel 9:219–235. Collins FS (1999) Shattuck lecture—Medical and societal consequences of the Human Genome Project. N Engl J Med 341:28–37. Croyle RT, Smith KR, Botkin JR, Baty B, Nash J (1997) Psychological responses to BRCA1 mutation testing: Preliminary findings. Health Psychol 16:63–72. Dorval M, Patenaude AF, Schneider KA, Kieffer SA, DiGianni L, Kalkbrenner KJ, Bromberg JI, Basili LA, Calzone K, Stopfer J, Weber BL, Garber JE (2000) Anticipated versus actual emotional reactions to disclosure of results of genetic tests for cancer susceptibility: Findings from p53 and BRCA1 testing programs. J Clin Oncol 18:2135–2142. Eisen A, Rebbeck TR, Wood WC, Weber BL (2000) Prophylactic surgery in women with a hereditary predisposition to breast and ovarian cancer. J Clin Oncol 18:1980–1995. Ford D, Easton DF, Bishop DT, Narod SA, Goldgar DE, and the Breast Cancer Linkage Consortium (1994) Risks of cancer in BRCA1-mutation carriers. Lancet 343:692–95. Frank TS, Manley SA, Olopade OI, Cummings S, Garber JE, Bernhardt B, Antman K, Russo D, Wood ME, Mullineau L, Isaacs C, Peshkin B, Buys S, Venne V, Rowley PT, Loader S, Offit K, Robson M, Hampel H, Brener D, Winer EP, Clark S, Weber B, Strong LC, Rieger P, McClure M, Ward BE, Shattuck-Eidens D, Oliphant A, Skolnick MH, Thomas A (1998) Sequence analysis of BRCA1 and BRCA2: Correlation of mutations with family history and ovarian cancer risk. J Clin Oncol 16:2417–2425. Greisinger AJ, Lorimor RJ, Aday LA, Winn RJ, Baile WF (1997) Terminally ill cancer patients: Their most important concerns. Cancer Pract 5:147–154.
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Hall MA, Rich SS (2000) Laws restricting health insurers’ use of genetic information: Impact on genetic discrimination. Am J Hum Genet 66:293–307. Hartmann LC, Schaid D, Sellers T, McDonnell S, Woods J, Sitta D, Frost M, Couch F, Jenkins R (2000) Bilateral prophylactic mastectomy (PM) in BRCA1/2 mutation carriers. Proc Am Assoc Cancer Res 41:222–223. Hilton BA (1993) Issues, problems, and challenges for families coping with breast cancer. Semin Oncol Nurs 9:88–100. Kornblith AB, Thaler HT, Wong G, Vlamis V, Lepore JM, Loseth DB, Hakes T, Hoskins WJ, Portenoy RK (1995) Quality of life of women with ovarian cancer. Gynecol Oncol 59:231–242. Lerman C, Narod S, Schulman K, Hughes C, Gomez-Caminero A, Bonney G, Gold K, Trock B, Main D, Lynch J, Fulmore C, Snyder C, Lemon SJ, Conway T, Tonin P, Lenoir G, Lynch H (1996) BRCA1 testing in families with hereditary breast-ovarian cancer: A prospective study of patient decision making and outcomes. JAMA 275:1885–1892. Lichter AS, Lippman ME, Danforth DN Jr, d’Angelo T, Steinberg SM, deMoss E, MacDonald HD, Reichert CM, Merino M, Swain SM, Cowan K, Gerber LH, Bader JL, Findlay PA, Schain W, Gorrel CR, Straus K, Rosenberg SA, Glatstein E (1992) Mastectomy versus breast-conserving therapy in the treatment of stage I and II carcinoma of the breast: A randomized trial at the National Cancer Institute. J Clin Oncol 10:976–983. Luker KA, Beaver K, Leinster SJ, Owens RG, Degner LF, Sloan JA (1995) The information needs of women newly diagnosed with breast cancer. J Adv Nurs 22:134–141. McKinnon WC, Baty BJ, Bennett RL, Magee M, Neufeld-Kaiser WA, Peters KF, Sawyer JC, Schneider KA (1997) Predisposition genetic testing for late-onset disorders in adults: A position paper of the National Society of Genetic Counselors. JAMA 278:1217–1220. Narod SA, Brunet JS, Ghadirian P, Robson M, Heimdal K, Neuhausen SL, Stoppa-Lyonnet D, Lerman C, Pasini B, de los Rios P, Weber B, Lynch H (2000) Tamoxifen and risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers: A case-control study. The Lancet 356:1876– 1881. Narod SA, Risch H, Moslehi R, Dorum A, Neuhausen S, Olsson H, Provencher D, Radice P, Evans G, Bishop S, Brunet JS, Ponder BA (1998) Oral contraceptives and the risk of hereditary ovarian cancer. N Engl J Med 339:424–428. Pierce LJ, Strawderman M, Narod SA, Eisen A, Dawson L, Gaffney D, Solin LJ, Nixon A, Garber J, Berg C, Isaacs C, Heimann R, Olopade OI, Haffy B, Weber BL (2000) Effect of radiotherapy after breast-conserving treatment in women with breast cancer and germline BRCA1/2 mutations. J Clin Oncol 18:3360–3369. Turner BC, Harrold E, Matloff E, Smith T, Gumbs AA, Beinfield M, Ward B, Skolnick M, Glazer PM, Thomas A, Haffty BG (1999) BRCA1/ BRCA2 germline mutations in locally recurrent breast cancer patients after lumpectomy and radiation therapy: Implications for breast-conserving management in patients with BRCA1/ BRCA2 mutations. J Clin Oncol 17:3017–3024. Ursin G, Henderson BE, Haile BW, Pike MC, Zhou N, Diep A, Bernstein L (1997) Does oral contraceptive use increase the risk of breast cancer in women with BRCA1/ BRCA2 mutations more than in other women? Cancer Res 57:3678–3681. U.S. Census Bureau (1999) Health Insurance Coverage: 1999. Available at http://www.census. gov/prod/2000pubs/p60-211.pdf Whelan T, Levine M, Gafni A, Sanders K, Willan A, Mirsky D, Schnider D, McCready D, Reid S, Kobylecky A, Reed K (1999) Mastectomy or lumpectomy? Helping women make informed choices. J Clin Oncol 17:1727–1735.
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Across the Spectrum: Case Studies in Genetic Counseling for Breast and Ovarian Cancer Tiffani A. DeMarco,1,2 Beth N. Peshkin,1 and Barbara M. Brogan1
We present three vignettes based on participants counseled as part of a clinical research program. These include a young unaffected woman at risk for a familial mutation, a newly diagnosed breast cancer patient, and a woman with recurrent ovarian cancer. Through the use of detailed vignettes, multifaceted issues that arise in cancer genetic counseling are highlighted. KEY WORDS: BRCA1/2; breast/ovarian cancer; genetic counseling; decision-making.
INTRODUCTION Since the cloning of the BRCA1 and BRCA2 genes in the mid-1990s, genetic counseling and testing have become widely available for individuals at risk for hereditary breast/ovarian cancer. Although several studies have demonstrated that individuals choose to undergo BRCA1/2 testing to obtain information for medical management (Clark et al., 2000), there are no prospective, long-term outcome data about the most effective means to screen for or reduce the cancer risk in carriers. In the absence of such data, guidelines are based primarily on expert clinical opinion (Burke et al., 1997a). In addition, the potential efficacy of certain prevention options, such as prophylactic mastectomy and oophorectomy, has recently been studied (Eisen et al., 2000). Another common reason that individuals seek genetic testing is to obtain information for relatives (Clark et al., 2000). Yet many women, especially those with breast or ovarian cancer, may be unprepared for the medical and emotional 1 Divison
of Cancer Control, Department of Oncology, Georgetown University – Lombardi Cancer Center, Washington, District of Columbia. 2 Correspondence should be directed to Tiffani DeMarco, Georgetown University – Lombardi Cancer Center, 2233 Wisconsin Avenue, NW Suite 317, Washington, District of Columbia, 20007; e-mail:[email protected]. 379 C 2001 National Society of Genetic Counselors, Inc. 1059-7700/01/1000-0379$19.50/1 °
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implications of test results for themselves and their relatives (Dorval et al., 2000). The process of informing family members about cancer risk can be formidable and, for relatives, the subtleties of “true negative results” versus “positive results” may lead to complex emotional responses. There may be psychological benefits associated with BRCA1/2 testing and, for most patients, there do not appear to be significant adverse effects associated with testing (Croyle et al., 1997; Lerman et al., 1996). However, responses to testing represent only one of the many issues faced by those seeking genetic counseling and testing. Psychological and family issues that individuals may have confronted, perhaps many years prior to or concomitant with genetic counseling, may profoundly affect their genetic testing experience. Many of these experiences can be elicited during client centered genetic counseling. Discussion of these factors can help patients make more informed decisions about testing, and prepare them for the potential implications of their decisions. The purpose of this paper is to provide a qualitative overview of some of the complex issues that may arise in genetic counseling for hereditary breast and ovarian cancer. The three case histories presented are drawn from families counseled as part of a clinical research program, and have been modified to protect confidentiality. These cases include a young unaffected woman at risk for a familial mutation, a woman with newly diagnosed breast cancer, and a woman with recurrent disease. YOUNG UNAFFECTED WOMAN Case History Sarah, a 27-year-old graduate student, was referred for genetic counseling following the identification of a BRCA1 mutation in her mother. Her mother had breast cancer at age 35 and was recently diagnosed with ovarian cancer at age 55. Additional family history information is depicted in Fig. 1. Pretest Counseling Summary Sarah was in her second semester of graduate school and had spent the past year at home caring for her mother. She wanted to pursue testing because she felt strongly about gathering as much knowledge as possible about her screening and prevention options. She indicated that although her time at home had brought her closer to her mother, it had also strengthened her desire to prevent herself from ever developing cancer. The session began with a review of the consent process and discussion of confidentiality and insurance discrimination. Sarah was not particularly concerned
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Fig. 1. Young unaffected proband.
about insurance coverage, as health insurance was provided through her school. However, she understood that when she enters the work force, she will not have complete protection against the use of genetic information for employment decisions and as part of an application for new health, life, and/or disability insurance. While she knew this was a potential risk, it was not a deterrent to her decision to undergo genetic testing. The remainder of the session focused on breast and ovarian cancer risks, and screening and prevention options for mutation carriers. Dominant inheritance and the 50% risk for inheriting the mutation that had previously been identified in her mother was discussed. The counselor emphasized that although carrying a mutation in BRCA1 increases the risk of developing cancer, it is not a cancer diagnosis. Sarah said that if she tested positive she would be concerned about her ability to undergo the recommended screening, as her current health insurance would not cover mammograms or ovarian screening for a woman of her age, nor did she feel that she wanted to have a mammogram annually for the rest of her life. She had not established a relationship with her physicians that would allow her to feel comfortable discussing her test results as justification for increased screening. These were issues that Sarah had not contemplated prior to the genetic counseling session. The counselor stressed that the recommendations for mutation carriers were only guidelines, and given Sarah’s young age, she needed to take into
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account the efficacy of screening and prevention methods and her current financial resources. The counselor discussed with Sarah that given that she was graduating next year, if a mutation were identified, she could consider having annual screening (i.e., clinical breast exams and routine gynecologic care) and then pursuing more rigorous screening when she had adequate health insurance. Sarah was aware of prophylactic surgery, but due to her young age this was not a major focus of discussion. She commented that she might decide to have children sooner rather than later if she tested positive, and would consider prophylactic oophorectomy after childbearing was completed. However, she currently felt that she would not consider prophylactic mastectomy. Sarah said that she was not inclined to take medication at this time, but may consider it in the future if she were to test positive. Also, at age 27, Sarah was not eligible for most chemoprevention studies. The role of the birth control pill as a prevention strategy in mutation carriers was also discussed. Sarah had been using oral contraceptives for 5 years and did not plan to discontinue their use. The counselor reviewed data indicating that use of oral contraceptives for more than 6 years in mutation carriers reduces ovarian cancer risk by as much as 60% (Narod et al., 1998). The possible increased risk for breast cancer in young female mutation carriers who use birth control pills was also explained (Ursin et al., 1997). Sarah mentioned that her mother’s recent ovarian cancer diagnosis had made her concerned about the effectiveness of treatment for this cancer. She said that while there may be an increased risk for breast cancer associated with the use of oral contraceptives, she viewed this risk very differently, because her mother, maternal grandmother, and aunt had survived several years following their breast cancer diagnoses. The counselor reminded Sarah that although the counseling had focused mainly on recommendations for individuals who carry a BRCA1 mutation, there was an equal likelihood that she would test negative for the mutation identified in her mother, and the implications of a true negative result were also reviewed. She said that while she wanted to have an optimistic attitude about the outcome of the testing, since the majority of the women in her mother’s family had developed cancer, she would probably be the “next in line.” Sarah was very concerned about her mother’s reaction if she tested positive, particularly feelings of guilt for having passed this mutation on to her daughter. Posttest Counseling Summary Sarah returned for her disclosure session approximately 1 month later, and was elated to learn that she did not carry the BRCA1 mutation identified in her mother. She now felt she could move on with her life at the pace she wanted, whereas previously she felt rushed to accomplish her goals before she developed cancer. Even at the young age of 27, she had convinced herself that a cancer diagnosis was probably inevitable. Because of this, she needed time to convince herself that
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the “cloud of cancer” was no longer hanging over her head. Sarah said she also no longer felt the urgency to have children as soon as possible. She was very thankful she underwent testing and planned to live her life on an unstructured timeline. Commentary Although this case had a “happy ending,” it illustrates several complex issues involved in counseling young unaffected female members of a family with a known deleterious BRCA1 or BRCA2 mutation. One of these major issues involves insurance discrimination. There are very few well-documented cases in which health insurers are using genetic test results in their underwriting decisions (Hall and Rich, 2000). Individuals with presymptomatic genetic conditions (such as unaffected individuals who carry a BRCA1 or BRCA2 mutation) have not reported difficulty in obtaining health insurance (Hall and Rich, 2000). In 1996, a federal law known as HIPAA (Health Insurance Portability and Accountability Act) prevented group health insurers from labeling presymptomatic genetic test results as “a pre-existing condition.” While this and other pending legislation provide protection for patients seeking genetic testing, fear of genetic discrimination still remains one of the primary deterrents to genetic testing (Clark et al., 2000). Although young unaffected patients may have concerns about possible future genetic discrimination, they may also not, at the time of their genetic counseling visit, be properly insured to receive the recommended screening. As demonstrated by Sarah’s situation, young women may be in a transitional period in their lives (such as between jobs, in school) and may therefore not have insurance or have little or no flexibility in their coverage. According to a 1999 survey, 15.5% of the U.S. population is uninsured, and individuals 18–24 years old were more likely than any other age group to lack coverage (a total of 29%) (U.S. Census Bureau, 1999). Not only may these young adults lack health insurance coverage, but they may also be without a physician with whom they have established a comfortable relationship. This lack of rapport may add to a patient’s discomfort in disclosing genetic test results to her provider to justify increased screening. For young women who test positive, counselors may make referrals to health care providers who are knowledgeable about the issues confronting mutation carriers but who may not be covered by a patient’s insurance plan. It is therefore necessary for the genetic counselor to be aware of a patient’s current health insurance situation and discuss alternatives, such as research studies. Even if a young mutation carrier is properly insured and in a position to pay for increased surveillance, she may become frustrated by the lack of concrete recommendations with regard to the age at which she should begin screening. Burke et al. (1997a) recommend clinical breast exams and mammography starting between ages 25 and 35. However, the efficacy of these surveillance options has not been proven in this young population. There has also been concern about the risk of radiation exposure for young women who begin mammography at such an
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early age (Abbott et al., 1998). This issue, coupled with the reduced sensitivity of mammography in younger women (Beam et al., 1996), may cause some patients to question the benefit of learning their genetic test results if there are no proven interventions. Therefore, counseling should include both a discussion of the benefits and limitations of surveillance guidelines. Patients should also understand that any potential risk of screening is outweighed by likely overall benefits (Burke et al., 1997b). A young woman’s decision to seek genetic testing may also be influenced by her family history of cancer (Lerman et al., 1996). As in other instances, an individual’s decision to undergo testing may be significantly affected by the types of cancer in her family, the number of affected relatives, and the ages at which they were diagnosed with cancer. Although this may be true for young women with cancer as well, it may have a greater impact on unaffected women, as their perception of survival may be based solely on their family history. As in Sarah’s case, it was apparent that her personal experience with her mother’s ovarian cancer had greatly affected her views regarding the efficacy of cancer screening and prevention options. The role of the genetic counselor is to facilitate discussion of the possible benefits, risks, and limitations of undergoing genetic testing at a young age. Counselors need to assess how a patient will react to a test result, positive or negative. The ramifications may be even more complex for a young unaffected woman who, depending on her results, may face an increased risk for breast and ovarian cancer over her lifetime or who may be relieved from the burden of her family’s legacy of cancer. YOUNG WOMAN WITH NEWLY DIAGNOSED BREAST CANCER Case History Julie, a 30-year-old Caucasian female newly diagnosed with breast cancer, was referred by her surgeon for genetic counseling and testing because of her young age at diagnosis and her family history of breast cancer (see Fig. 2). She had already undergone an excisional biopsy of a mass in her right breast; however, because she had positive margins, a wide reexcision or a mastectomy was indicated. Julie was scheduled for genetic counseling immediately after her first surgery, and was informed that if she desired testing, results would be available in approximately 3 weeks. Pretest Counseling Summary At Julie’s first counseling visit, only 8 days after she received the diagnosis of breast cancer, she was anxious. She was overwhelmed with the information about
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Fig. 2. Newly diagnosed proband.
treatment options she had gathered. She asked many questions about chemotherapy, radiation therapy, and surgical options. The counselor explained to Julie that the majority of her questions could not be answered until after additional surgery when her physicians would have information about prognostic factors and treatment options. Because Julie required another surgery to treat her breast cancer, she wanted to have as much information as possible to make an informed decision about what procedure to choose. Julie’s personal and family history was suggestive of hereditary breast cancer. Once she understood this, she became more concerned about developing a new primary breast cancer. However, she said that her surgeon felt confident that breast conserving surgery was an appropriate option to treat her current breast cancer. But, at age 30, Julie worried about feeling anxious if she opted
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for breast conserving surgery and close surveillance. Her current breast cancer was not detected by mammography, nor did her physician detect any masses during her breast exam performed just 2 months before Julie discovered the lump herself. She could not imagine hearing the words “You have breast cancer” a second time, and wanted to do everything possible to reduce her risk. For these reasons, Julie felt certain that she would choose bilateral mastectomies if she tested positive for a BRCA1 or BRCA2 mutation. Another focus of the genetic counseling session was a discussion regarding the difference between a cancer recurrence and the risk of developing a new primary breast cancer in the ipsilateral or contralateral breast. The counselor explained that the risks associated with carrying a BRCA1 or BRCA2 mutation are for a new primary breast cancer. It was further explained that the risk for a recurrence was based on prognostic factors that Julie could discuss in greater detail with her oncologist. It was discussed that her genetic test results would not influence recommendations about adjuvant treatment for her current breast cancer. After discussing the risk for developing another new primary breast cancer, the counselor also talked with Julie about ovarian cancer risks associated with a BRCA1 or BRCA2 mutation (Frank et al., 1998). Because she was still reeling from her new breast cancer diagnosis, she could not thoroughly process information about other cancer risks at the time of her counseling session. Nevertheless, Julie decided to undergo genetic testing because she felt that it would provide her with another piece of information to factor into her current decision-making process. She also felt that finding out that she had an inherited susceptibility to breast cancer would answer her question as to why she and her family members had developed breast cancer at young ages.
Posttest Counseling Summary The counselor met again with Julie 3 weeks later and informed her that she carried a deleterious mutation in BRCA1. Even though she was certain during her pre-counseling session that she would choose bilateral mastectomies if a mutation was identified, she was not as confident after hearing her results. After several conversations with the counselor and her surgeon, Julie decided to undergo breast conserving surgery and 7 weeks of radiation therapy. Julie was satisfied with her decision and would be undergoing close surveillance for breast cancer, consisting of monthly breast self-exam, physician breast exam every 3–6 months, and annual mammograms. Julie planned to consult with a gynecologic oncologist about recommendations for ovarian cancer screening but might consider prophylactic oophorectomy after completing her family. She also informed her sisters about the mutation that had been identified and the options available for genetic counseling and testing.
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Commentary Women with a mutation in BRCA1 or BRCA2 have up to a 65% risk for developing a new primary cancer in their contralateral breast (Ford et al., 1994), and an elevated risk of ipsilateral breast cancer (Turner et al., 1999). Given the increased risks for developing a new primary breast cancer, it is easy to understand why mutation carriers struggle with a surgery decision. In the general population, randomized trials of mastectomy versus breast conserving surgery have demonstrated no difference in long-term survival (Lichter et al., 1992). Therefore, surgical decisions are often made based on surgeon’s recommendations and quality of life issues. Whelan et al. (1999) reported that a “decision board” developed to assist surgeons in presenting information to patients regarding mastectomy and breast conserving surgery facilitated shared decision making between the surgeon and the patient. Similar tools may also be developed to assist mutation carriers with the difficult decisions they encounter at the time of a new breast cancer diagnosis. A decision-aid may be particularly helpful for newly diagnosed mutation carriers because the very high risks for a second breast cancer may influence a patient’s decision about breast conserving surgery. Newly diagnosed patients who are found to have a mutation in BRCA1 or BRCA2 may opt for bilateral mastectomies to reduce their risk of a subsequent breast cancer. They may also be influenced by recent data that indicate that BRCA1/2 mutation carriers who underwent bilateral prophylactic mastectomies reduced their risk for developing breast cancer by 90% (Hartmann et al., 2000). Because of the high risk for contralateral breast cancer in mutation carriers and the efficacy of prophylactic bilateral mastectomies, this surgical choice is a reasonable option for the newly diagnosed patient. However, factors such as the extensive nature of the surgery, recovery time, and possible alternatives for reconstruction also need to be considered. The process of genetic counseling and testing prior to making a surgery decision was still helpful to Julie, even though she did not choose to undergo more extensive breast surgery. BRCA1/2 status may be factored into future surgical decisions. For example, women may choose bilateral mastectomies after having completed cancer treatment. However, drawbacks to delaying bilateral mastectomies include the prior completion of radiation treatments and the need to undergo additional surgical procedures. In general, a nondirective counseling approach facilitates discussion of these issues and assists patients in making a decision about which surgical option is best for them, not the one the counselor might make or believes the patient should make. In addition to addressing surgical options, genetic counseling for newly diagnosed breast cancer patients often involves a complex discussion of the difference between a recurrence of a woman’s current breast cancer and her risk for developing a new primary breast cancer. As illustrated in Julie’s case, her surgeon made it clear that lumpectomy with radiation was a reasonable option for treating her current breast cancer. There are no data at present that indicate that breast conserving
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surgery followed by radiation therapy is contraindicated in BRCA1/2 mutation carriers to treat the cancer they have. For example, Pierce et al. (2000) found that there was no significant difference in local recurrence and/or 5-year survival rate between patients with a BRCA1/2 mutation versus sporadic controls undergoing radiation after breast conservation. While longer follow-up is needed, these data may be helpful when discussing treatment options with newly diagnosed patients. A recent study suggested that use of tamoxifen significantly reduced the risk of contralateral breast cancer in patients with a BRCA1 or BRCA2 alteration (Narod et al., 2000). Although these data are encouraging, use of tamoxifen to treat newly diagnosed breast cancer patients is still a complex issue, particularly for those women whose tumors may be estrogen receptor negative. Overall, it is essential that the newly diagnosed patient comprehends that the results of BRCA1/2 testing are currently not a major factor in determining use of adjuvant treatment and subsequent prognosis. Because newly diagnosed patients are often focused on their impending surgical decision and subsequent treatment, they may not be in a position to assimilate information about future cancer risk, particularly ovarian cancer. The majority of patients affected with breast cancer who seek genetic counseling have already made their surgical decisions and in most cases have completed treatment. Thus, they may be better able to comprehend information about risk for future cancers. Many newly diagnosed patients want only to treat the breast cancer they have and deal with any future cancer risk at a later time. Their primary motivation is to move past the initial shock of a breast cancer diagnosis and get on with their lives. Therefore, it is important for the counselor to strike a balance between addressing the patient’s new breast cancer, their primary concern, and feeling compelled to discuss other cancer risks, which can be addressed after a patient has undergone surgery. While it is apparent that some mutation carriers may struggle with their surgical decision at the time of a new diagnosis, there is no information in the literature about genetic counseling and testing for newly diagnosed breast cancer patients. Therefore, the informational and supportive needs of these patients are not well known or understood. Women newly diagnosed with breast cancer perceive information about the likelihood of cure, the spread of the disease, and treatment options as the most important information needed at the time of diagnosis (Luker et al., 1995). It is important to allow patients the opportunity to express their concerns, so that they can focus on the genetic counseling issues. For this reason, sessions with newly diagnosed breast cancer patients often last 2–3 hours. It is also valuable for the counselor to have some knowledge of clinical oncology and breast cancer treatment options. This helps to build rapport with the patient, assists in identifying pertinent issues, and allows the session to be tailored to meet the needs of the patient. Women newly diagnosed with breast cancer are a challenging group to counsel. Counselors should not assume that all young women with newly diagnosed breast cancer will be interested in having genetic testing in order to make surgery decisions. Patients may opt for genetic testing but proceed with surgery before
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learning the results. Some patients may choose to learn the results prior to making a surgery decision, while others may choose to have genetic testing after they have completed treatment for their breast cancer. RECURRENT/METASTATIC DISEASE Case History Anne, a 51-year-old Caucasian woman with recurrent ovarian cancer, was referred for genetic counseling by her gynecologic/oncologist. In 1996 she had been diagnosed at age 48 with Stage IIIC cystadenocarcinoma for which she underwent debulking surgery followed by chemotherapy. Recently, liver metastases were discovered, for which Anne was participating in a clinical trial of a new chemotherapy regimen. The remainder of her medical history was unremarkable. Family history information is depicted in Fig. 3. Pretest Counseling Summary Anne requested that her genetic counseling appointment occur during one of the weeks when she was not receiving treatment, and that it be limited to an hour due to her fatigue. To accommodate her requests, family and medical history information was obtained through mailed forms and telephone. During the history
Fig. 3. Proband with recurrent ovarian cancer.
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collection, Anne revealed that she had not had a mammogram since her initial diagnosis, and had never had colon screening. During the genetic counseling session Anne appeared haggard and indicated that her main reason for wanting testing was to gain information for her daughters. Anne never directly raised issues about her prognosis, but described her attempts to “tie up things” in her life, which she hoped that the treatment would buy her enough time to accomplish. She requested that her BRCA1/2 results be provided to her over the phone in light of her condition. The pretest genetic counseling session focused on risk assessment and preparing her for the high likelihood that a BRCA1 or BRCA2 mutation would be identified; however, the possibility of a negative result was also explained. Autosomal dominant inheritance was reviewed, and it was emphasized that relatives other than her daughters were at risk, including her son, siblings, and cousins. Previously she had thought that a positive test result would have implications only for her daughters. Cancer risks and management options were discussed primarily as this information would apply to relatives. It was acknowledged that Anne was appropriately concentrating on her current treatment and that medical implications to her would need to be considered in the context of her general health. The recommendations for annual mammograms and colon cancer screening were framed as they might apply to her family members. Anne questioned why her doctors never recommended that she undergo ovarian screening or have her ovaries removed in light of her family history and the information she had just learned about the association of breast and ovarian cancers with BRCA1/2 mutations. The counselor explained that information about hereditary breast/ovarian cancer was still very new and that without documentation of a complete family history, it may be difficult to identify this syndrome, or the possible transmission of risk through the paternal lineage. In addition, screening for ovarian cancer is imperfect (Burke et al., 1997a), and residual cancer risks remain even after prophylactic oophorectomy. Anne’s anger and disappointment at not being advised of her ovarian cancer risk were acknowledged, as was her desire to find a reason why she developed cancer and what she could have done to avoid it. These reactions were somewhat defused by the idea that her family may use information about her test results proactively. Anne discussed how she would communicate information about her test results to her family and how she would cope if any of her children tested positive. She again remarked that her hope was that if she tested positive, the information would be used constructively. She stated that learning such a result would be a “relief” in that she would understand the likely reason why she got cancer, would know that she had some concrete information to share with her relatives, and that there would be no medical implications to her in light of her current condition. She felt the news could not affect her as adversely as having learned that she had metastatic ovarian cancer. In addition, she stated that her family was close knit and very supportive.
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Posttest Counseling Summary Four weeks after the initial genetic counseling session, the genetic counselor called Anne with her results, which revealed that she had a deleterious mutation in BRCA1. Anne had recently returned from a 5-day stay in the hospital after a bout with pneumonia and was still quite weak. Thus, the telephone discussion lasted less than 15 min. Most of the time was spent responding to Anne’s concerns about how her relatives could get information about obtaining genetic counseling. A short summary letter was sent to Anne, primarily reviewing implications to her relatives and logistics of obtaining genetic counseling/testing in their locales. Commentary The optimal approach to genetic counseling about hereditary breast cancer often involves two in-person visits for genetic counseling. Because of the severity of the patient’s illness, the initial session was streamlined by obtaining medical and family history information by phone prior to the visit. This allowed the counselor to focus on family and psychosocial issues during the in-person visit. The chance of finding a BRCA1 or BRCA2 mutation in this family was estimated to be about 90% (Frank et al., 1998). Therefore, it was appropriate to structure much of the discussion around the strong possibility that the patient would test positive, and what the familial implications would be. Although it was not stated by the patient herself, it was clear that her prognosis was poor and that she may not live more than a few months. Thus, to maintain rapport with this patient it would have been inappropriate to discuss in detail the medical implications of a positive test result to the patient herself. For example, Anne was made aware that prophylactic mastectomy is an option for at-risk relatives, but not necessarily for her. In addition, her doctors had recommended that she obtain a mammogram after her initial treatment was completed, but she never followed up. Given her health, neither her doctors nor she was concerned with her breast cancer risk, and no doctor had broached the subject of other screening, such as colon cancer screening. The counselor provided support for her during the session, acknowledged how difficult this time was for her, and assisted Anne in sorting through the impact her testing decision would have on her family. Finally, telephone disclosure of test results was an acceptable alternative in this case as Anne was well prepared for the information and had a good support system in place. Women with ovarian cancer, particularly those with declining health, may experience significant psychological distress (Kornblith et al., 1995). Women in the terminal stages of cancer may also be dealing with their spirituality, family concerns, and physical pain (Greisinger et al., 1997). Clinicians providing genetic counseling must understand the relative significance of the genetic testing experience. Tailoring the genetic counseling sessions, including streamlining the information and considering exceptions to standard protocol procedures, may be
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acceptable and desirable for some patients. However, providers are still obliged to engage in the informed consent process and ensure that patients understand the implications of the information imparted to them. A recent study showed that cancer patients may underestimate their emotional reactions to a positive result (Dorval et al., 2000), thus underscoring the need to provide anticipatory guidance to all individuals, especially cancer patients, at the time of their initial genetic counseling session. Although counseling can never fully prepare people for how they may ultimately react to genetic test results, it will allow them to contemplate the complex issues that are likely to arise. DISCUSSION This paper examined genetic counseling for breast and ovarian cancer susceptibility across a spectrum of patient issues: a healthy unaffected woman at risk for a familial mutation, a newly diagnosed breast cancer patient, and finally a terminally ill patient. Although genetic counseling for these three patients involves addressing the specific needs of these individuals, there are also several common themes. These themes include the uncertainty that patients must face regarding risk assessment, possible cancer risks and the lack of proven screening and prevention options. This complexity underscores the importance of collecting and validating data about probabilities of being a BRCA1/2 carrier, cancer risks associated with mutations in these genes, and the efficacy of screening modalities and prevention options. Obtaining this information will contribute to more informed patient decision making. It is hoped that the cancer risks associated with BRCA1/2 mutations may eventually be individually tailored based on a patient’s ethnic background and the specific mutation identified, along with other genetic and environmental risk modifiers. In addition, long-term outcome data about the efficacy of surveillance, prophylactic surgery, and chemoprevention options in mutation carriers will be beneficial to patients as they strive to make informed decisions about medical management. A second theme involves the disclosure of test results to relatives. A cancer diagnosis, whether a new breast cancer or recurrent ovarian cancer, creates emotional challenges for the patient as well as for family members (Hilton, 1993; Kornblith et al., 1995). As a result, women may not wish to burden their relatives with the complex issues surrounding their genetic test results. However, for some women, information for relatives may be the primary motivator for their seeking testing. Genetic testing is likely to have an impact on all family members, and therefore helping patients develop an appropriate plan to inform their relatives is a vital component of genetic counseling. Finally, it is expected that the sequencing of the human genome will eventually give rise to clinically translatable information through the identification of new genes predisposing to adult onset conditions such as heart disease, diabetes,
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and many forms of cancer (Collins, 1999). Therefore, over the next several years there will be heightened interest in genetic testing for cancer predisposition. The lessons learned from genetic counseling for hereditary breast cancer underscore the importance of comprehensive pre- and posttest counseling and the need to educate and involve a multidisciplinary group of providers to impart such services (McKinnon et al., 1997). It is hoped that as genetic testing becomes more widely available, broader legislation on the state and federal levels will decrease the perceived threat of genetic discrimination, a concern that may be a significant barrier in patient decision making and genetic testing utilization. The counseling issues (see Table I) and themes discussed in this paper are applicable to other genetic conditions. The experience with counseling women at high risk for hereditary breast and ovarian cancer will help refine genetic counseling and follow-up, thus maximizing the potential benefits while minimizing the possible adverse effects of genetic testing. Table I. Medical and Psychosocial Issues Faced by Three Genetic Counseling Patient Populations
Medical issues
Young unaffected female
Young, with newly diagnosed breast cancer
Recurrent cancer/ poor prognosis
Integration of cumulative cancer risk estimates
Surgical and adjuvant treatment decisions
Tailoring medical info and shifting emphasis to patient’s agenda Recognizing prognosis and the implications of testing
Vague screening recommendations
Distinguishing between new primary and recurrence Difficulty assessing Addressing risk of 2nd the positives and cancers—including negatives of hormonal ovarian cancer options Potential problems Time pressure related accessing health care to surgical decision making Short-/long-term decision making Psychosocial issues
Possibility of genetic discrimination Body image Family planning
Distress associated with new diagnosis Sexuality and body image Survival concerns
Impact of family history Family communication of cancer re: diagnosis and genetic test results Assimilation of test result
Family communication Addressing “why” cancer occurred Understanding of how testing fits into patient’s need to “tie-up” issues
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ACKNOWLEDGMENTS The authors thank all of the men and women who participated in our research studies. In addition, we are grateful to Michael Begleiter, MS, Holly Ishmael, MS, Anne O’Connor, RN, MSN, AOCN, and Kenneth Tercyak, PhD, for their review of the manuscript and insightful comments. Also, special thanks to Annalisa DialinoFelix, BS, for preparing the pedigrees, and to Claudine Isaacs, MDCM, Medical Director of our research program. This research was supported by Department of Defense Grant DAMB 1796-C-6069, Grant RO1 HG01846 from the National Human Genome Research Institute, and Grant RO1 CA74861-03 from the National Cancer Institute/National Institutes of Health. (Principal Investigators: Caryn Lerman, PhD, Chanita Hughes, PhD, and Marc Schwartz, PhD). Additional support was provided by institutional funds from the Lombardi Cancer Center. REFERENCES Abbott DW, Freeman ML, Holt JT (1998) Double-strand break repair deficiency and radiation sensitivity in BRCA2 mutant cancer cells. J Natl Cancer Inst 90:978–985. Beam CA, Layde PM, Sullivan DC (1996) Variability in the interpretation of screening mammograms by US radiologists: Findings from a national sample. Arch Intern Med 156:209–213. Burke W, Daly M, Garber J, Botkin J, Kahn MJ, Lynch P, McTiernan A, Offit K, Perlman J, Petersen G, Thomson E, Varricchio C (1997a) Recommendations for follow-up care of individuals with an inherited predisposition to cancer: II. BRCA1 and BRCA2. JAMA 277:997–1003. Burke W, Daly M, Garber J, Botkin J, Kahn MJ, Lynch P, McTiernan A, Offit K, Perlman J, Petersen G, Thomson E, Varricchio C (1997b) Benefits and risks of screening mammography in women with BRCA1 and BRCA2 mutations. JAMA 278:290–291. Clark S, Bluman L, Borstelmann N, Regan K, Winer E, Rimer BK, Skinner CS (2000) Patient motivation, satisfaction, and coping in genetic counseling and testing for BRCA1 and BRCA2. J Genet Counsel 9:219–235. Collins FS (1999) Shattuck lecture—Medical and societal consequences of the Human Genome Project. N Engl J Med 341:28–37. Croyle RT, Smith KR, Botkin JR, Baty B, Nash J (1997) Psychological responses to BRCA1 mutation testing: Preliminary findings. Health Psychol 16:63–72. Dorval M, Patenaude AF, Schneider KA, Kieffer SA, DiGianni L, Kalkbrenner KJ, Bromberg JI, Basili LA, Calzone K, Stopfer J, Weber BL, Garber JE (2000) Anticipated versus actual emotional reactions to disclosure of results of genetic tests for cancer susceptibility: Findings from p53 and BRCA1 testing programs. J Clin Oncol 18:2135–2142. Eisen A, Rebbeck TR, Wood WC, Weber BL (2000) Prophylactic surgery in women with a hereditary predisposition to breast and ovarian cancer. J Clin Oncol 18:1980–1995. Ford D, Easton DF, Bishop DT, Narod SA, Goldgar DE, and the Breast Cancer Linkage Consortium (1994) Risks of cancer in BRCA1-mutation carriers. Lancet 343:692–95. Frank TS, Manley SA, Olopade OI, Cummings S, Garber JE, Bernhardt B, Antman K, Russo D, Wood ME, Mullineau L, Isaacs C, Peshkin B, Buys S, Venne V, Rowley PT, Loader S, Offit K, Robson M, Hampel H, Brener D, Winer EP, Clark S, Weber B, Strong LC, Rieger P, McClure M, Ward BE, Shattuck-Eidens D, Oliphant A, Skolnick MH, Thomas A (1998) Sequence analysis of BRCA1 and BRCA2: Correlation of mutations with family history and ovarian cancer risk. J Clin Oncol 16:2417–2425. Greisinger AJ, Lorimor RJ, Aday LA, Winn RJ, Baile WF (1997) Terminally ill cancer patients: Their most important concerns. Cancer Pract 5:147–154.
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