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A literature review of the psychological impact of genetic testing on breast cancer patients
Patient Education and Counseling 62 (2006) 13–20 www.elsevier.com/locate/pateducou
Review
A literature review of the psychological impact of genetic testing on breast cancer patients Kathryn J. Schlich-Bakker a,*, Herman F.J. ten Kroode a, Margreet G.E.M. Ausems b a
Department of Medical Psychology, University Medical Centre Utrecht, Utrecht, The Netherlands b Department of Medical Genetics, University Medical Centre Utrecht, Utrecht, The Netherlands Received 7 April 2005; received in revised form 23 August 2005; accepted 25 August 2005
Abstract Objective: Easier access and increased awareness results in more referral for genetic testing for hereditary breast cancer in healthy at-risk women and breast cancer patients. To investigate the psychological impact of genetic testing on breast cancer patients, literature pertaining to this group was reviewed. Method: Medline and PsychInfo databases were searched over the period 1995–2004 for studies aimed at breast cancer patients referred for genetic testing. Qualitative and quantitative psychological outcome measures were identified. Results: Eight papers were identified focusing on women affected by breast cancer and undergoing genetic counseling and DNA testing. Conclusion: Genetic testing does not lead to an increase in psychological distress in breast cancer patients. However, a recent breast cancer diagnosis adds to general and cancer-specific distress prior to genetic counseling and after DNA test disclosure. Practice implications: Clinicians need to be aware of possible high psychological distress and additional counseling needs of recently diagnosed breast cancer patients taking part in genetic testing. Further research should focus on patients who decline genetic counseling or receive an inconclusive test result, including age upon and time since diagnosis. # 2005 Elsevier Ireland Ltd. All rights reserved. Keywords: Breast cancer patients; Genetic testing; Psychological impact; Review
Contents 1. 2. 3.
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Introduction . . . . . . . . . . . . . . . . . Methods . . . . . . . . . . . . . . . . . . . . Results . . . . . . . . . . . . . . . . . . . . . 3.1. Design . . . . . . . . . . . . . . . . 3.2. Participants . . . . . . . . . . . . . 3.3. Outcome measures . . . . . . . . 3.4. Main findings. . . . . . . . . . . . 3.4.1. Prospective design . . 3.4.2. Retrospective design . Discussion and conclusions . . . . . . . 4.1. Discussion . . . . . . . . . . . . . . 4.2. Conclusions . . . . . . . . . . . . .
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* Corresponding author at: Department of Medical Psychology, University Medical Center Utrecht, PO Box 85060, 3508 AB Utrecht, The Netherlands. Tel.: +31 30 253 9021. E-mail address: [email protected] (K.J. Schlich-Bakker). 0738-3991/$ – see front matter # 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.pec.2005.08.012
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4.3. Practice implications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1. Introduction An estimated 5–10% of all breast cancers are likely to be inherited with autosomal dominant transmission [1]. With the identification of two breast cancer susceptibility genes, BRCA1 [2] and BRCA2 [3], genetic testing is now available for breast cancer patients. In general, DNA testing is offered to affected patients based on their family history or earlyonset of the disease [4]. Pre-symptomatic DNA testing is available to healthy relatives of breast cancer patients in whom a mutation has been detected since inherited mutations in BRCA1 and BRCA2 are associated with an increased risk for breast and ovarian cancer [5]. Individuals in whom a gene mutation has been identified are offered regular monitoring or preventive measures in order to decrease morbidity [6]. The past 10 years have been characterized by a steadily growing interest in genetic counseling for hereditary breast cancer [7]. Most individuals who apply for genetic counseling do so on their own initiative and comprise a select group of healthy women at high risk for developing breast cancer [8,9]. These women feel vulnerable to breast cancer, are more likely to consider prophylactic surgery, and perceive testing to have fewer limitations [10]. An important reason for interest in testing is a high self-perceived risk of having a BRCA1 gene mutation [11], while in a Dutch group of individuals with a family history of cancer other reasons for genetic testing were to obtain certainty (67%), to be able to take preventive action (61%), and to estimate the risk for children (47%) [12]. Women who apply for genetic testing on their own initiative may be well prepared for the test result and thus represent a less vulnerable group [13]. Increased awareness among the general population, patients and health providers, and the easier access to genetic facilities may further increase referral for genetic testing for hereditary breast cancer. Besides healthy at-risk women, breast cancer patients will apply or be referred, even during a course of treatment [14,15]. However, this group may be more psychologically vulnerable since they may exhibit more cancer-related anxiety due to their recent diagnosis and treatment [16–19]. To investigate the impact of genetic testing on women diagnosed with breast cancer the literature on this topic was reviewed. The investigation included both emotional and cognitive psychological measures.
2. Methods The Medline and PsychInfo databases for the period January 1995 to October 2004 were searched using the
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following keywords in combination: breast cancer, affected, genetic testing or counseling, diagnostic testing and breast cancer clinic. The search strategies were based on the keywords being in a heading or text. Adding terms related to the following psychological outcome measures narrowed the search down: psychological impact, anxiety, distress, motivation, risk perception, knowledge and attitude. In addition, publications of key authors in the field and the reference lists of identified publications, as well as linked articles within the databases were searched. Studies meeting the following criteria were included: (a) the study aim concerned breast cancer patients taking part in genetic counseling and testing, as opposed to studies focusing on healthy women and using breast cancer patients as a subpopulation; (b) psychological outcome measures either emotional or cognitive, assessing the impact of DNAtesting, were used; (c) the study was published in a peerreviewed journal in the English language. Studies on the prevalence of mutations in breast cancer patients or focusing on pre-symptomatic DNA testing, as well as any case reports were excluded. The identified studies were analyzed according to design, participants, outcome measures and main findings. With respect to design, studies were put into two categories: prospective or retrospective and the referral pathway of participants was recorded. Study groups were analyzed by size, percentage of affected patients, mean age of participants, mean time since diagnosis, and country in which the study had taken place. Used outcome measures were categorized by their qualitative or quantitative nature according to the descriptions given and whether emotional or cognitive in nature. Finally, main findings pertaining to breast cancer patients were summarized.
3. Results Eight papers were identified describing seven data sets focusing on women affected by breast cancer and undergoing genetic counseling and DNA testing. The studies were published between 2000 and 2004 (Tables 1 and 2). 3.1. Design Five studies had a prospective design [20–24] (Table 1), four of which included a follow up with additional measures one to 12 months later [20,21,23,24]. Three studies [25–27] had a retrospective design reporting on measures taken during mutation searching [27], 17 months after test disclosure [25], and one to 9 years after blood sampling for DNA testing [26] (Table 2).
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Table 1 Prospective studies on the psychological impact of genetic testing on breast cancer patients Reference
Designa
Participantsa,b
Outcome measures
Main findings
Bish et al. [20]
Questionnaire by mail prior to first appointment; 2 wk, 6 and 12 mo after first appointment; referral not specified
N = 203; 24% affected; 73% unaffected; 89% bc, 2% oc, 9% bc and oc; age: 42.3 yr (18–79 yr); Post: 5 yr (4 mo–32 yr) (UK)
Quantitative; perceived risk for bc; perceived risk for mutation; STAI; GHQ-28; cancer worry scale
Randall et al. [21]
Questionnaire by mail prior to first appointment; 2 wk–2 mo after first appointment, questionnaire by mail; 3–6 mo after first appointment questionnaire by mail and structured telephone interview; referral not specified
N = 60; 100% affected; 100% bc; age: not specified; post: 11% <3 mo, 19% 3–12 mo, 44% 1–5 yr, 26% > 5 yr (AUS)
Quantitative; knowledge genetic testing BRCA1/2; Pros and cons genetic testing; STAI; IES; BDI
Van Roosmalen 1 wk after blood taken and 2 wk et al. [22] after test result; questionnaire by mail; referral not specified
N = 368; 52% affected; 48% unaffected; 90% bc, 8% oc, 2% bc and oc; age: 47.4 yr (affected); 39.4 yr (unaffected); post: 4.7 yr (NETH)
Quantitative; STAI; CES-D; IES; treatment choice; decision making; evaluation treatment options
Schwartz et al. [23]
Quantitative; Perceived N = 279; 67% affected; risk for bc and oc; 33% unaffected; 100% bc and/or oc; age: not specified; IES; HSCL post: not specified (USA)
No changes in any psychological measures except decrease bc worry; affected women more oc worry with no changes over time; decrease in perceived likelihood of carrying mutation with higher perceptions when affected with bc No difference at baseline on psychological adjustment between patients seeking genetic counseling and patients who were not; patients seeking genetic counseling more knowledge about genetic testing at baseline with a higher increase of this knowledge at short-term follow up; knowledge increase was not accompanied by an increase in anxiety or depression; after test disclosure, anxiety applied to treatment rather than waiting for test result Hint towards profound increase in general and cancer-related distress; carriers diagnosed 1 year prior testing higher general en cancerspecific distress at baseline and follow up; more carriers intended to have prophylactic surgery and valued it more highly; at follow-up carriers increased their strength of treatment preference and decreased decision uncertainty No effect of test result on psychological measures or perceived bc or oc risk in affected women
Wood et al. [24]
Structured telephone interview prior to education and counselling; 1 mo and 6 mo after genetic test result structured telephone interview; 100% self-referral Questionnaire by mail prior to initial consultation; 2 wk after first consultation questionnaire; 1 mo after genetic test result questionnaire; referral not specified
N = 35; 100% affected; 92% bc, 3% oc, 5% bc and oc; Age: 46 yr (25–73 yr); Post: 21% <1 yr, 78% >1 yr (USA)
Quantitative; IES; HSCL; Qualitative; Satisfaction counseling and testing; not specified; knowledge genetic testing BRCA1/2; attitude genetic testing BRCA1/2
Decreased anxiety unrelated to DNA test result; testing negative reduced intrusive thoughts; testing positive showed trend towards increase in intrusive thoughts; if diagnosed <1 year before testing, more cancer-specific intrusive thoughts prior counseling and more genetic testing intrusive thoughts prior DNA test disclosure; in 64% genetic counseling extremely helpful in future medical decisionmaking; need for assistance in communicating with family
STAI: state-trait anxiety inventory, GHQ-28: general health questionnaire, HADS: hospital anxiety and depression scale, CED-D: center for epidemiologic studies depression scale, IES: impact of event scale, BDI: beck depression inventory, HSCL: Hopkins symptom checklist-25. a wk: weeks, mo: months, yr: years. b bc: breast cancer, oc: ovarian cancer, cc: colon cancer, age: mean age of study group, post: mean time between last cancer diagnosis and genetic counseling, AUS: Australia, NETH: Netherlands.
Only two studies specified the referral pathway [23,25], in one study all women participating in genetic testing were self-referred [23] and in the other study participants were self-referred, referred by a relative or by their physician [25].
3.2. Participants The study populations varied in size between 30 and 368 participants. Three studies [20,22,23] described a population
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Table 2 Retrospective studies on the psychological impact of genetic testing on breast cancer patients Reference
Design
a
Claes 17 mo after DNA test et al. [25] result semi-structured interview, questionnaire; 44% relative, 37% physician; 19% self referral
Participants
a,b
N = 62; 100% affected; 82% bc, 11% oc, 6% bc and oc; age: 52.7 yr; post: not specified (BEL)
Outcome measures
Main findings
Quantitative; STAI; IES; SCL-90; UCL; perceived seriousness/control; Qualitative; willingness to apply; reason to apply for testing; impact test result
No effect DNA test result on general or cancer-specific distress or perceived seriousness or control of bc; carriers felt less control towards early detection and curability of oc and had concern for negative emotional impact and their children; non-carriers were relieved; patients with inconclusive test result form heterogeneous group: some misinterpreted result as absence of genetic predisposition, some relieved but still aware of increased risk, others continuing uncertainty and felt less in control; genetic testing mainly for relatives Qualitative; reason to apply for testing; Mutation searching or waiting for DNA test Hallowell 1–9 yrs after or during N = 30; 100% affected; reaction to counseling and testing; result was not anxiety provoking; main et al. [26] mutation searching 90% bc, 7% oc, 3% experience waiting for test result reasons for genetic testing: to inform family open in-dept interview; gynae; age: 44–62 members, general altruism, curiosity and referral not specified (carriers), 41–66 obtain information for risk management; (waiting), 39–71 (incon) carriers benefit from end to uncertainty and yr; post: 1.5-31 (carriers), report difficulties in informing family as 0.5–20 (waiting), 1.5–7 well as concern for potential anxiety; (incon) yr (UK) inconclusive test result was followed by a range of emotional reactions and misinterpretation of test result Qualitative; Impact cancer diagnosis/ Responses to genetic testing mediated Hallowell After or during mutation N = 30; 100% affected; treatment; reaction to genetic test by former cancer experiences and reason 90% bc, 7% oc, 3% et al. [27] searching open in-dept result; reason to apply for testing for testing; responses not influenced by gynae; age: 39–71 yr; interview; referral not perceptions of family history prior to post: 6 mo-31 yr (UK) specified cancer diagnosis, time since cancer diagnosis or disclosure or DNA test result STAI: State-Trait Anxiety Inventory, IES: Impact of Event Scale, SCL-90: Symptom-Checklist, UCL: Utrecht Coping List. a wk: weeks, mo: months, yr: years. b bc: breast cancer, oc: ovarian cancer, gynae: gynaecological cancer, carriers: cancer patients with positive DNA test result, waiting: cancer patients waiting for DNA test result, incon: cancer patients with inconclusive DNA test result, Age: mean age of study group, Post: mean time between last cancer diagnosis and genetic counseling, BEL: Belgium.
of over 200 and five studies [21,24–27] included less than 100 participants. Five studies pertained only to women affected by cancer [21,24–27]. Three studies used control groups consisting of healthy individuals from high-risk families [23], healthy individuals divided into different risk groups of carrying a genetic mutation [20] or unaffected mutation carriers [22]. In one study the affected group consisted of only breast cancer patients [23]. In the other studies the affected groups comprised 82–92% breast cancer patients and 8–18% patients with either ovarian cancer, or a combination of breast and ovarian cancer (Tables 1 and 2). The mean age of patients varied between 39.4 and 52.7 years with a range of 18–79 years [20,22,24,25]. One study included breast cancer patients diagnosed before the age of 50 years with no further specification [24]. None of the other studies noted patients’ age upon diagnosis. Two studies [20,22] noted the mean time between cancer diagnosis and genetic counseling of 5 and 4.7 years, respectively, with a range of 4 months to 32 years. Four studies [21,24,26,27]
provided ranges between >3 months and 7 years and 2 studies did not specify the time since the last cancer diagnosis [23,25]. Three studies were performed in the UK [20,26,27], two studies included participants from the USA [23,24], the remaining three studies took place in Australia [21], the Netherlands [22] and Belgium [25]. 3.3. Outcome measures Four studies used only quantitative measures [20–23] and two studies used only qualitative measures [26,27], while two studies used quantitative and qualitative measures [24,25]. Of the 23 identified measures, eight pertained to emotional aspects, 13 to cognitive aspects and two measures consisted of emotional as well as cognitive aspects. Emotional aspects included general anxiety [20–25], cancer-specific distress [21–25], depression [21,22–24], support needs [26,27], emotional reaction to genetic
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counseling and testing [26,27], genetic testing distress [24], cancer worry [20] and experience waiting for test result [26]. Cognitive aspects included risk perception for breast cancer [20,23], reason to apply for testing [25–27], pros and cons for genetic testing [21], knowledge about genetic testing for BRCA1/2 [21,24], attitudes towards genetic testing for BRCA1/2 [24], risk perception for carrying a mutation [20], satisfaction with genetic counseling [24], impact of cancer diagnosis and treatment [27], perceived seriousness and control [25], treatment choice [22], decision making [22], evaluation of treatment options [22] and willingness to apply for genetic testing [25]. The two measures pertaining to emotional as well as cognitive aspects were: coping strategy [25] and the impact of the diagnostic test result [25]. 3.4. Main findings 3.4.1. Prospective design Three prospective studies found no influence of DNA test result on any of the psychological measures [20,21,23]. Bish et al. reported a decrease in breast cancer worry in breast cancer patients [20], while a decrease in anxiety unrelated to the DNA test result was also found [24]. However, Van Roosmalen et al. found an increase in general and cancerrelated distress in affected mutation carriers following the DNA test result [22]. Breast cancer patients diagnosed less than 1 year ago demonstrated more cancer-specific intrusive thoughts prior to counseling. In addition, this group had more genetic testing-specific intrusive thoughts prior to DNA test disclosure [24]. Van Roosmalen et al. described elevated levels of general and cancer-specific distress at baseline and after testing in recently diagnosed mutation carriers compared to carriers diagnosed longer than 1 year ago [22]. Bish et al. [20] and Schwartz et al. [23] found no effect of DNA test result on perceived cancer risk in affected women. The perceived likelihood for carrying a BRCA1/2 mutation decreased after testing. Higher perceptions were found in affected women and unaffected women at high risk [20]. The main reasons for affected women to apply for genetic testing were preventing cancer in the family and understanding their own illness. Sixty-four percent of affected women found the genetic counseling process extremely helpful for future medical decision-making. Fifty-four percent suggested communicating the test result to family as an area in which they needed more help [24]. Randall et al. reported a trend towards greater knowledge about genetic testing for BRCA1/ 2 at baseline in affected women from high-risk families seeking genetic counseling. These patients demonstrated a larger increase in knowledge at short-term follow up with no accompanying increase in anxiety or depression [21]. 3.4.2. Retrospective design The DNA test result had no effect on general or cancerspecific distress [25]. Nor did mutation searching and waiting for a test result provoke anxiety [26]. The test result
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also did not influence affected women’s responses to genetic testing since these were mediated by former experiences with cancer and their reasons for being tested [27]. Claes et al. [25] reported a concern for the health of children as the main reason for testing. In addition, Hallowell et al. [26] described the importance of curiosity and risk management. Two studies reported women’s reactions to the DNA test result. Carriers felt more in control [25] and benefited from having an end to uncertainty [26], but they also experienced a negative emotional impact and were concerned for their children [25]. Hallowell et al. [26] described the difficulty breast cancer patients experienced when having to inform family about the confirmatory DNA test result. Affected women from high-risk families who turned out to be noncarriers were relieved [25]. An inconclusive test result was sometimes misinterpreted as an absence of a genetic predisposition [25,26]. Affected women with an inconclusive test result expressed a range of emotional reactions [26] including relief, although they were still aware of their increased risk, had continuing uncertainty, and felt less in control [25].
4. Discussion and conclusions 4.1. Discussion The reported vulnerability of breast cancer patients diagnosed less than 1 year prior to genetic counseling and testing may be due to the recent breast cancer diagnosis and treatment [16–19]. In addition to negative psychological reactions caused by diagnosis and surgery, those due to radiotherapy [28] and chemotherapy [29,30] may play an important role. Despite this vulnerability, recently diagnosed patients seem as interested in genetic testing as patients diagnosed longer ago [31]. Julian-Reynier et al. [32] found that this understandable higher anxiety at baseline decreased after genetic counseling, even dropping to a level similar to that seen in patients diagnosed more than 1 year ago. This suggests that recently diagnosed patients, in particular, benefit from genetic counseling reducing their anxiety. Taking into account that satisfaction with genetic counseling has a positive influence on level of anxiety [32], this effect may be optimized by providing counseling that fits the specific needs of women recently diagnosed with breast cancer. There may also be specific counseling needs for affected women with a high-perceived risk for developing a second breast cancer or ovarian cancer. In described studies genetic counseling and testing did not affect patients’ perceived risk for breast cancer [20,23], as found by Bleiker et al. [33]. Butow et al. [34] concluded that genetic counseling is successful in improving the accuracy of women’s cancer risk perception in the short term, although many continue to overestimate their risk. As these personal perceptions prove resistant to standard education and counseling, affected
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women with a high perceived risk for cancer need tailored counseling. This is to make sure that an unrealistically highperceived risk is not motivating patients’ decision-making process in genetic testing and subsequent treatment. Findings by Bluman et al. [31] reveal a need to improve breast cancer patients’ basic knowledge on hereditary breast cancer and the consequences of carrying a BRCA1/2 gene mutation. Breast cancer patients from high-risk families undergoing genetic testing had a higher knowledge on genetic testing at baseline. Compared to affected women not taking part in genetic testing, these patients also demonstrated more increase in this knowledge at short-term follow up not accompanied by an increase in anxiety or depression [21]. Breast cancer patients not taking part in genetic testing probably know less about BRCA1/2 therefore we should not expect them to take the initiative in requesting counseling. By leaving the initiative to this group of patients means they will not learn more about this topic. We therefore need ways to reach affected women with a genetic risk who do not take part in genetic counseling. Bluman et al. [31] found that breast cancer patients demonstrated more interest in genetic testing when advised by their physician. For adequate referral, physicians treating breast cancer patients need to be made fully aware of the criteria of a genetic risk [35] and the process of genetic counseling and testing. In adopting an active approach, we must take into account that breast cancer patients who know little about BRCA1/2 will be unprepared for the possibility of a gene mutation and might not be psychologically well equipped to deal with genetic risk information [36]. Loader et al. [37] found index patients most prone to distress due to breast cancer risk assessment and genetic testing. This was supported by the finding that distress in women is greater if they are the first in the family to be tested for a BRCA gene mutation [38]. Accordingly, we should expect women recently diagnosed with breast cancer who are actively approached for genetic testing, and are the first in their family to be tested for a BRCA gene mutation, to be an extremely vulnerable group. There is a need for further research concerning this group. The evaluated studies did not comment on the timing of genetic testing. Patients had been diagnosed with cancer up to 32 years ago and less than 1 year before genetic testing. Weitzel et al. [14] and Schwartz et al. [15] focused on the impact of approaching breast cancer patients for genetic testing who were still in the process of making a decision about surgery. In these studies no reference was made to the possible psychological impact of genetic testing shortly after receiving a breast cancer diagnosis, while these patients may be expected to be even more psychologically vulnerable. After genetic testing, Van Roosmalen et al. [22] found more affected carriers intended to have prophylactic surgery; they valued it more highly and demonstrated a stronger preference for treatment and less uncertainty. Wood et al. [24] reported that 64% of breast cancer patients found genetic counseling and testing extremely helpful in future medical decision-making. Further research is needed to
identify vulnerable newly diagnosed breast cancer patients taking part in genetic counseling and testing in order to determine which patients need tailored counseling and to provide guidelines on how to approach them for genetic counseling and DNA testing. This review was limited to studies focusing on breast cancer patients taking part in genetic counseling and testing. Therefore, studies that report on healthy women taking part in genetic testing for BRCA1/2 with breast cancer patients as part of the study group were not included. In addition, studies focusing on breast cancer patients participating in genetic counseling and in which the process of genetic testing was not specified were excluded form this review. Five of the reviewed studies had a longitudinal design most with a short follow-up with a large variance. Of the eight emotional aspects, six were measured using a standardized tool but none of the thirteen cognitive aspects were measured using a standardized tool. The growing interest in genetic testing means there is a need for standardized tools. Overall the studies described large study groups. Three studies included a control group of unaffected women [20,22,23] and only one study made a comparison between affected women opting for genetic testing and affected women who did not [21]. Only one study provided the mean age at which the affected group was diagnosed with cancer [24]. This may play an important role considering the influence an individual’s life-stage has on the emotional impact of a cancer diagnosis [39]. In addition, there was a large variance among the studies in time between diagnosis and genetic counseling. It is necessary to study a homogenous group to provide accurate information because time since diagnoses appears to play an important role in the level of general and cancer-specific anxiety prior to and after testing. None of the studies focused on patients who declined genetic testing. In research among unaffected individuals, Lerman et al. [40] found those who declined genetic testing vulnerable. Geer et al. [41] reported patients’ concerns for health insurability, cost, emotional impact, no perceived benefit and time commitment as barriers for cancer genetic counseling. Anxiety and the anticipation of negative emotional reactions to the test result have also been identified as important reasons to decline genetic testing [42–44]. Whereas Lodder et al. [45] found that unaffected women who declined pre-symptomatic DNA testing were more likely to have thought about the decision thoroughly than deny the whole issue due to high anxiety. Questions remain on why breast cancer patients decline genetic testing and what the consequences are. Another group needing more research is that of breast cancer patients receiving an inconclusive test result. In affected women the inconclusive test result was followed by a range of emotional reactions and misinterpretation of the test result [25,26]. This is expected to be a vulnerable group since these women request counseling to gain certainty yet
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are left in uncertainty [12,46], as opposed to the carriers who said they benefited from having an end to their uncertainty [26]. Due to differences between countries we may not be able to generalize these findings to all breast cancer patients eligible for genetic counseling. The uptake for testing for hereditary breast cancer varies between countries, possibly reflecting cultural differences in attitudes towards genetic testing and related issues like health insurance and discrimination [33,40,47,48]. 4.2. Conclusions The present investigation describes eight studies focusing on the psychological aspects of genetic testing in women diagnosed with breast cancer. Most studies used a prospective design applied to a large study group. In general, genetic testing did not lead to an increase of psychological distress in breast cancer patients, although two studies reported an increase in general and cancer-specific distress after receiving a positive DNA test result. A recent breast cancer diagnosis added to the level of general and cancer-specific distress prior to genetic counseling and after receiving a DNA test result. In one study breast cancer patients’ responses to their genetic risk of future disease were not influenced by time since diagnosis. An inconclusive test result was sometimes misinterpreted and led to continuing uncertainty and a range of emotional reactions. Mutation carriers reported an end to the uncertainty playing part in their treatment decisionmaking process. Perceived risk for carrying a mutation decreased after testing, but there was no change in perceived breast cancer risk. The main reason for affected women to have a genetic test was to make relatives more alert to their own risk. Affected women found it difficult to inform family members about the DNA test result. 4.3. Practice implications Clinicians need to be aware of the possible high psychological distress in recently diagnosed breast cancer patients taking part in genetic counseling and testing. Additional counseling may be needed for patients diagnosed less than 1 year ago and patients with an unrealistic high perceived risk for a second breast cancer or ovarian cancer to manage high levels of distress and to assist these patients in their decision-making process. Further research on the psychological functioning of breast cancer patients taking part in genetic testing is needed to support more specific recommendations for this group. Important aspects to take into consideration are age upon diagnosis and time between diagnosis and genetic testing. With respect to research design, more longitudinal studies with long-term follow up are needed and a control group of affected women not referred for genetic testing should be used. More specific research recommendations pertain to the vulnerable groups identified.
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First, research must identify possible risk factors for high psychological distress in recently diagnosed breast cancer patients in order to select patients who need tailored counseling and to provide guidelines on when and how best to approach them for genetic testing. In order to optimize satisfaction with tailored counseling and its anxietyreducing effect, we need more studies focusing on the specific needs of these patients, as well as patients who have a high perceived risk for another breast cancer or ovarian cancer. Second, tools should be designed to improve basic knowledge about BRCA1/2 among breast cancer patients. Third, Among the actively approached breast cancer patients, those who decline genetic testing or receive an inconclusive test result are of particular interest for further study.
Acknowledgment We thank Jackie Senior for critically reading the manuscript.
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[31] Bluman LG, Rimer BK, Berry DA, Borstelmann N, Iglehart JD, Regan K, et al. Attitudes, knowledge, and risk perceptions of women with breast and/or ovarian cancer considering testing for BRCA1 and BRCA2. J Clin Oncol 1999;17:1040–6. [32] Julian-Reynier C, Eisinger F, Chabal F, Aurran Y, Bignon Y-J, Nogue`s C, et al. Time elapsing from cancer diagnosis and anxiety in women attending cancer genetic clinics. Oncol Rep 1998;5:885–8. [33] Bleiker EMA, Hahn DEE, Aaronson NK. Psychological issues in cancer genetics. Current status and future directions. Acta Oncol 2003;42:276–86. [34] Butow PN, Lobb EA, Meiser B, Barratt A, Tucker KM. Psychological outcomes and risk perception after genetic testing and counseling in breast cancer: a systematic review. Med J Aust 2003;178:77–81. [35] Wa´rla´m-Rodenhuis CC, Koot VCM, Van der Luijt RB, Vasen HFA. Ausems MGEM. A prospective study on predictive factors linked to the presence of BRCA1 and BRCA2 mutations in breast cancer patients. Eur J Cancer 2005;41:1409–15. [36] Van Zuuren FJ. The standard of neutrality during genetic counseling: an empirical investigation. Patient Educ Couns 1997;32:69–79. [37] Loader S, Shields CG, Rowley PT. Impact of genetic testing for breastovarian cancer susceptibility. Gen Test 2004;8:1–12. [38] Smith KR, West JA, Croyle RT, Botkin JR. Familial context of genetic testing for cancer susceptibility: moderating effect of siblings’ test results on psychological distress one to two weeks after BRCA1 mutation testing. Cancer Epidemiol Biomarkers Prev 1999;8:385–92. [39] Rowland JH. Developmental stage and adaptation: adult model. In: Holland JC, Rowland JH, editors. Handbook of psycho-oncology: psychological care of the medical patient with cancer. New York: Oxford University Press; 1990. p. 25–43. [40] Lerman C, Hughes C, Lemon SJ, Main D, Snyder C, Durham C, et al. What you do not know can hurt you: adverse psychologic effects in members of BRCA1-linked and BRCA2-linked families who decline genetic testing. J Clin Oncol 1998;16:1650–4. [41] Geer KP, Ropka ME, Cohn WF, Jones SM, Miesfeldt S. Factors influencing patients’ decisions to decline cancer genetic counseling services. J Genetic Couns 2001;10:25–40. [42] Codori AM, Petersen GM, Miglioretti DL, Larkin EK, Bushey MT, Young C, et al. Attitudes toward colon cancer gene testing: factors predicting test uptake. Cancer Epidemiol Biomarkers Prev 1999; 8:345–51. [43] Decruyenaere M, Evers-Kiebooms G, Boogaerts A, Cloosterman T, Cassiman JJ, Demyttenaere K, et al. Non-participation in predictive testing for Huntington’s disease: individual decision-making, personality and avoidant behaviour in the family. Eur J Hum Genet 1997; 5:351–63. [44] Steenstraten IM vd, Tibben A, Roos RA, van de Kamp JJ, Niemeijer MF. Predictive testing for Huntington disease: non-participants compared with participants in the Dutch program. Am J Hum Genet 1994;55:618–625. [45] Lodder L, Frets PG, Trijsburg RW, Klijn JGM, Seynaeve C, Tilanus MMA, et al. Attitudes and distress levels in women at risk to carry a BRCA1/BRCA2 gene mutation who decline genetic testing. Am J Med Genet 2003;119A:266–72. [46] Van Zuuren FJ, Van Schie ECM, Van Baaren NK. Uncertainty in the information provided during genetic counseling. Patient Educ Couns 1997;32:129–39. [47] Peterson EA, Milliron KJ, Lewis KE, Goold SD, Merajver SD. Health insurance and discrimination concerns and BRCA1/2 testing in a clinic population. Cancer Epidemiol Biomarkers Prev 2002;11:79–87. [48] Armstrong K, Weber B, FitzGerald G, Hershey JC, Pauly MV, Lemaire J, et al. Life insurance and breast cancer risk assessment. Am J Med Genet 2003;120:359–64.
Review
A literature review of the psychological impact of genetic testing on breast cancer patients Kathryn J. Schlich-Bakker a,*, Herman F.J. ten Kroode a, Margreet G.E.M. Ausems b a
Department of Medical Psychology, University Medical Centre Utrecht, Utrecht, The Netherlands b Department of Medical Genetics, University Medical Centre Utrecht, Utrecht, The Netherlands Received 7 April 2005; received in revised form 23 August 2005; accepted 25 August 2005
Abstract Objective: Easier access and increased awareness results in more referral for genetic testing for hereditary breast cancer in healthy at-risk women and breast cancer patients. To investigate the psychological impact of genetic testing on breast cancer patients, literature pertaining to this group was reviewed. Method: Medline and PsychInfo databases were searched over the period 1995–2004 for studies aimed at breast cancer patients referred for genetic testing. Qualitative and quantitative psychological outcome measures were identified. Results: Eight papers were identified focusing on women affected by breast cancer and undergoing genetic counseling and DNA testing. Conclusion: Genetic testing does not lead to an increase in psychological distress in breast cancer patients. However, a recent breast cancer diagnosis adds to general and cancer-specific distress prior to genetic counseling and after DNA test disclosure. Practice implications: Clinicians need to be aware of possible high psychological distress and additional counseling needs of recently diagnosed breast cancer patients taking part in genetic testing. Further research should focus on patients who decline genetic counseling or receive an inconclusive test result, including age upon and time since diagnosis. # 2005 Elsevier Ireland Ltd. All rights reserved. Keywords: Breast cancer patients; Genetic testing; Psychological impact; Review
Contents 1. 2. 3.
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Introduction . . . . . . . . . . . . . . . . . Methods . . . . . . . . . . . . . . . . . . . . Results . . . . . . . . . . . . . . . . . . . . . 3.1. Design . . . . . . . . . . . . . . . . 3.2. Participants . . . . . . . . . . . . . 3.3. Outcome measures . . . . . . . . 3.4. Main findings. . . . . . . . . . . . 3.4.1. Prospective design . . 3.4.2. Retrospective design . Discussion and conclusions . . . . . . . 4.1. Discussion . . . . . . . . . . . . . . 4.2. Conclusions . . . . . . . . . . . . .
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* Corresponding author at: Department of Medical Psychology, University Medical Center Utrecht, PO Box 85060, 3508 AB Utrecht, The Netherlands. Tel.: +31 30 253 9021. E-mail address: [email protected] (K.J. Schlich-Bakker). 0738-3991/$ – see front matter # 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.pec.2005.08.012
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4.3. Practice implications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1. Introduction An estimated 5–10% of all breast cancers are likely to be inherited with autosomal dominant transmission [1]. With the identification of two breast cancer susceptibility genes, BRCA1 [2] and BRCA2 [3], genetic testing is now available for breast cancer patients. In general, DNA testing is offered to affected patients based on their family history or earlyonset of the disease [4]. Pre-symptomatic DNA testing is available to healthy relatives of breast cancer patients in whom a mutation has been detected since inherited mutations in BRCA1 and BRCA2 are associated with an increased risk for breast and ovarian cancer [5]. Individuals in whom a gene mutation has been identified are offered regular monitoring or preventive measures in order to decrease morbidity [6]. The past 10 years have been characterized by a steadily growing interest in genetic counseling for hereditary breast cancer [7]. Most individuals who apply for genetic counseling do so on their own initiative and comprise a select group of healthy women at high risk for developing breast cancer [8,9]. These women feel vulnerable to breast cancer, are more likely to consider prophylactic surgery, and perceive testing to have fewer limitations [10]. An important reason for interest in testing is a high self-perceived risk of having a BRCA1 gene mutation [11], while in a Dutch group of individuals with a family history of cancer other reasons for genetic testing were to obtain certainty (67%), to be able to take preventive action (61%), and to estimate the risk for children (47%) [12]. Women who apply for genetic testing on their own initiative may be well prepared for the test result and thus represent a less vulnerable group [13]. Increased awareness among the general population, patients and health providers, and the easier access to genetic facilities may further increase referral for genetic testing for hereditary breast cancer. Besides healthy at-risk women, breast cancer patients will apply or be referred, even during a course of treatment [14,15]. However, this group may be more psychologically vulnerable since they may exhibit more cancer-related anxiety due to their recent diagnosis and treatment [16–19]. To investigate the impact of genetic testing on women diagnosed with breast cancer the literature on this topic was reviewed. The investigation included both emotional and cognitive psychological measures.
2. Methods The Medline and PsychInfo databases for the period January 1995 to October 2004 were searched using the
19 19 19
following keywords in combination: breast cancer, affected, genetic testing or counseling, diagnostic testing and breast cancer clinic. The search strategies were based on the keywords being in a heading or text. Adding terms related to the following psychological outcome measures narrowed the search down: psychological impact, anxiety, distress, motivation, risk perception, knowledge and attitude. In addition, publications of key authors in the field and the reference lists of identified publications, as well as linked articles within the databases were searched. Studies meeting the following criteria were included: (a) the study aim concerned breast cancer patients taking part in genetic counseling and testing, as opposed to studies focusing on healthy women and using breast cancer patients as a subpopulation; (b) psychological outcome measures either emotional or cognitive, assessing the impact of DNAtesting, were used; (c) the study was published in a peerreviewed journal in the English language. Studies on the prevalence of mutations in breast cancer patients or focusing on pre-symptomatic DNA testing, as well as any case reports were excluded. The identified studies were analyzed according to design, participants, outcome measures and main findings. With respect to design, studies were put into two categories: prospective or retrospective and the referral pathway of participants was recorded. Study groups were analyzed by size, percentage of affected patients, mean age of participants, mean time since diagnosis, and country in which the study had taken place. Used outcome measures were categorized by their qualitative or quantitative nature according to the descriptions given and whether emotional or cognitive in nature. Finally, main findings pertaining to breast cancer patients were summarized.
3. Results Eight papers were identified describing seven data sets focusing on women affected by breast cancer and undergoing genetic counseling and DNA testing. The studies were published between 2000 and 2004 (Tables 1 and 2). 3.1. Design Five studies had a prospective design [20–24] (Table 1), four of which included a follow up with additional measures one to 12 months later [20,21,23,24]. Three studies [25–27] had a retrospective design reporting on measures taken during mutation searching [27], 17 months after test disclosure [25], and one to 9 years after blood sampling for DNA testing [26] (Table 2).
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Table 1 Prospective studies on the psychological impact of genetic testing on breast cancer patients Reference
Designa
Participantsa,b
Outcome measures
Main findings
Bish et al. [20]
Questionnaire by mail prior to first appointment; 2 wk, 6 and 12 mo after first appointment; referral not specified
N = 203; 24% affected; 73% unaffected; 89% bc, 2% oc, 9% bc and oc; age: 42.3 yr (18–79 yr); Post: 5 yr (4 mo–32 yr) (UK)
Quantitative; perceived risk for bc; perceived risk for mutation; STAI; GHQ-28; cancer worry scale
Randall et al. [21]
Questionnaire by mail prior to first appointment; 2 wk–2 mo after first appointment, questionnaire by mail; 3–6 mo after first appointment questionnaire by mail and structured telephone interview; referral not specified
N = 60; 100% affected; 100% bc; age: not specified; post: 11% <3 mo, 19% 3–12 mo, 44% 1–5 yr, 26% > 5 yr (AUS)
Quantitative; knowledge genetic testing BRCA1/2; Pros and cons genetic testing; STAI; IES; BDI
Van Roosmalen 1 wk after blood taken and 2 wk et al. [22] after test result; questionnaire by mail; referral not specified
N = 368; 52% affected; 48% unaffected; 90% bc, 8% oc, 2% bc and oc; age: 47.4 yr (affected); 39.4 yr (unaffected); post: 4.7 yr (NETH)
Quantitative; STAI; CES-D; IES; treatment choice; decision making; evaluation treatment options
Schwartz et al. [23]
Quantitative; Perceived N = 279; 67% affected; risk for bc and oc; 33% unaffected; 100% bc and/or oc; age: not specified; IES; HSCL post: not specified (USA)
No changes in any psychological measures except decrease bc worry; affected women more oc worry with no changes over time; decrease in perceived likelihood of carrying mutation with higher perceptions when affected with bc No difference at baseline on psychological adjustment between patients seeking genetic counseling and patients who were not; patients seeking genetic counseling more knowledge about genetic testing at baseline with a higher increase of this knowledge at short-term follow up; knowledge increase was not accompanied by an increase in anxiety or depression; after test disclosure, anxiety applied to treatment rather than waiting for test result Hint towards profound increase in general and cancer-related distress; carriers diagnosed 1 year prior testing higher general en cancerspecific distress at baseline and follow up; more carriers intended to have prophylactic surgery and valued it more highly; at follow-up carriers increased their strength of treatment preference and decreased decision uncertainty No effect of test result on psychological measures or perceived bc or oc risk in affected women
Wood et al. [24]
Structured telephone interview prior to education and counselling; 1 mo and 6 mo after genetic test result structured telephone interview; 100% self-referral Questionnaire by mail prior to initial consultation; 2 wk after first consultation questionnaire; 1 mo after genetic test result questionnaire; referral not specified
N = 35; 100% affected; 92% bc, 3% oc, 5% bc and oc; Age: 46 yr (25–73 yr); Post: 21% <1 yr, 78% >1 yr (USA)
Quantitative; IES; HSCL; Qualitative; Satisfaction counseling and testing; not specified; knowledge genetic testing BRCA1/2; attitude genetic testing BRCA1/2
Decreased anxiety unrelated to DNA test result; testing negative reduced intrusive thoughts; testing positive showed trend towards increase in intrusive thoughts; if diagnosed <1 year before testing, more cancer-specific intrusive thoughts prior counseling and more genetic testing intrusive thoughts prior DNA test disclosure; in 64% genetic counseling extremely helpful in future medical decisionmaking; need for assistance in communicating with family
STAI: state-trait anxiety inventory, GHQ-28: general health questionnaire, HADS: hospital anxiety and depression scale, CED-D: center for epidemiologic studies depression scale, IES: impact of event scale, BDI: beck depression inventory, HSCL: Hopkins symptom checklist-25. a wk: weeks, mo: months, yr: years. b bc: breast cancer, oc: ovarian cancer, cc: colon cancer, age: mean age of study group, post: mean time between last cancer diagnosis and genetic counseling, AUS: Australia, NETH: Netherlands.
Only two studies specified the referral pathway [23,25], in one study all women participating in genetic testing were self-referred [23] and in the other study participants were self-referred, referred by a relative or by their physician [25].
3.2. Participants The study populations varied in size between 30 and 368 participants. Three studies [20,22,23] described a population
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Table 2 Retrospective studies on the psychological impact of genetic testing on breast cancer patients Reference
Design
a
Claes 17 mo after DNA test et al. [25] result semi-structured interview, questionnaire; 44% relative, 37% physician; 19% self referral
Participants
a,b
N = 62; 100% affected; 82% bc, 11% oc, 6% bc and oc; age: 52.7 yr; post: not specified (BEL)
Outcome measures
Main findings
Quantitative; STAI; IES; SCL-90; UCL; perceived seriousness/control; Qualitative; willingness to apply; reason to apply for testing; impact test result
No effect DNA test result on general or cancer-specific distress or perceived seriousness or control of bc; carriers felt less control towards early detection and curability of oc and had concern for negative emotional impact and their children; non-carriers were relieved; patients with inconclusive test result form heterogeneous group: some misinterpreted result as absence of genetic predisposition, some relieved but still aware of increased risk, others continuing uncertainty and felt less in control; genetic testing mainly for relatives Qualitative; reason to apply for testing; Mutation searching or waiting for DNA test Hallowell 1–9 yrs after or during N = 30; 100% affected; reaction to counseling and testing; result was not anxiety provoking; main et al. [26] mutation searching 90% bc, 7% oc, 3% experience waiting for test result reasons for genetic testing: to inform family open in-dept interview; gynae; age: 44–62 members, general altruism, curiosity and referral not specified (carriers), 41–66 obtain information for risk management; (waiting), 39–71 (incon) carriers benefit from end to uncertainty and yr; post: 1.5-31 (carriers), report difficulties in informing family as 0.5–20 (waiting), 1.5–7 well as concern for potential anxiety; (incon) yr (UK) inconclusive test result was followed by a range of emotional reactions and misinterpretation of test result Qualitative; Impact cancer diagnosis/ Responses to genetic testing mediated Hallowell After or during mutation N = 30; 100% affected; treatment; reaction to genetic test by former cancer experiences and reason 90% bc, 7% oc, 3% et al. [27] searching open in-dept result; reason to apply for testing for testing; responses not influenced by gynae; age: 39–71 yr; interview; referral not perceptions of family history prior to post: 6 mo-31 yr (UK) specified cancer diagnosis, time since cancer diagnosis or disclosure or DNA test result STAI: State-Trait Anxiety Inventory, IES: Impact of Event Scale, SCL-90: Symptom-Checklist, UCL: Utrecht Coping List. a wk: weeks, mo: months, yr: years. b bc: breast cancer, oc: ovarian cancer, gynae: gynaecological cancer, carriers: cancer patients with positive DNA test result, waiting: cancer patients waiting for DNA test result, incon: cancer patients with inconclusive DNA test result, Age: mean age of study group, Post: mean time between last cancer diagnosis and genetic counseling, BEL: Belgium.
of over 200 and five studies [21,24–27] included less than 100 participants. Five studies pertained only to women affected by cancer [21,24–27]. Three studies used control groups consisting of healthy individuals from high-risk families [23], healthy individuals divided into different risk groups of carrying a genetic mutation [20] or unaffected mutation carriers [22]. In one study the affected group consisted of only breast cancer patients [23]. In the other studies the affected groups comprised 82–92% breast cancer patients and 8–18% patients with either ovarian cancer, or a combination of breast and ovarian cancer (Tables 1 and 2). The mean age of patients varied between 39.4 and 52.7 years with a range of 18–79 years [20,22,24,25]. One study included breast cancer patients diagnosed before the age of 50 years with no further specification [24]. None of the other studies noted patients’ age upon diagnosis. Two studies [20,22] noted the mean time between cancer diagnosis and genetic counseling of 5 and 4.7 years, respectively, with a range of 4 months to 32 years. Four studies [21,24,26,27]
provided ranges between >3 months and 7 years and 2 studies did not specify the time since the last cancer diagnosis [23,25]. Three studies were performed in the UK [20,26,27], two studies included participants from the USA [23,24], the remaining three studies took place in Australia [21], the Netherlands [22] and Belgium [25]. 3.3. Outcome measures Four studies used only quantitative measures [20–23] and two studies used only qualitative measures [26,27], while two studies used quantitative and qualitative measures [24,25]. Of the 23 identified measures, eight pertained to emotional aspects, 13 to cognitive aspects and two measures consisted of emotional as well as cognitive aspects. Emotional aspects included general anxiety [20–25], cancer-specific distress [21–25], depression [21,22–24], support needs [26,27], emotional reaction to genetic
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counseling and testing [26,27], genetic testing distress [24], cancer worry [20] and experience waiting for test result [26]. Cognitive aspects included risk perception for breast cancer [20,23], reason to apply for testing [25–27], pros and cons for genetic testing [21], knowledge about genetic testing for BRCA1/2 [21,24], attitudes towards genetic testing for BRCA1/2 [24], risk perception for carrying a mutation [20], satisfaction with genetic counseling [24], impact of cancer diagnosis and treatment [27], perceived seriousness and control [25], treatment choice [22], decision making [22], evaluation of treatment options [22] and willingness to apply for genetic testing [25]. The two measures pertaining to emotional as well as cognitive aspects were: coping strategy [25] and the impact of the diagnostic test result [25]. 3.4. Main findings 3.4.1. Prospective design Three prospective studies found no influence of DNA test result on any of the psychological measures [20,21,23]. Bish et al. reported a decrease in breast cancer worry in breast cancer patients [20], while a decrease in anxiety unrelated to the DNA test result was also found [24]. However, Van Roosmalen et al. found an increase in general and cancerrelated distress in affected mutation carriers following the DNA test result [22]. Breast cancer patients diagnosed less than 1 year ago demonstrated more cancer-specific intrusive thoughts prior to counseling. In addition, this group had more genetic testing-specific intrusive thoughts prior to DNA test disclosure [24]. Van Roosmalen et al. described elevated levels of general and cancer-specific distress at baseline and after testing in recently diagnosed mutation carriers compared to carriers diagnosed longer than 1 year ago [22]. Bish et al. [20] and Schwartz et al. [23] found no effect of DNA test result on perceived cancer risk in affected women. The perceived likelihood for carrying a BRCA1/2 mutation decreased after testing. Higher perceptions were found in affected women and unaffected women at high risk [20]. The main reasons for affected women to apply for genetic testing were preventing cancer in the family and understanding their own illness. Sixty-four percent of affected women found the genetic counseling process extremely helpful for future medical decision-making. Fifty-four percent suggested communicating the test result to family as an area in which they needed more help [24]. Randall et al. reported a trend towards greater knowledge about genetic testing for BRCA1/ 2 at baseline in affected women from high-risk families seeking genetic counseling. These patients demonstrated a larger increase in knowledge at short-term follow up with no accompanying increase in anxiety or depression [21]. 3.4.2. Retrospective design The DNA test result had no effect on general or cancerspecific distress [25]. Nor did mutation searching and waiting for a test result provoke anxiety [26]. The test result
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also did not influence affected women’s responses to genetic testing since these were mediated by former experiences with cancer and their reasons for being tested [27]. Claes et al. [25] reported a concern for the health of children as the main reason for testing. In addition, Hallowell et al. [26] described the importance of curiosity and risk management. Two studies reported women’s reactions to the DNA test result. Carriers felt more in control [25] and benefited from having an end to uncertainty [26], but they also experienced a negative emotional impact and were concerned for their children [25]. Hallowell et al. [26] described the difficulty breast cancer patients experienced when having to inform family about the confirmatory DNA test result. Affected women from high-risk families who turned out to be noncarriers were relieved [25]. An inconclusive test result was sometimes misinterpreted as an absence of a genetic predisposition [25,26]. Affected women with an inconclusive test result expressed a range of emotional reactions [26] including relief, although they were still aware of their increased risk, had continuing uncertainty, and felt less in control [25].
4. Discussion and conclusions 4.1. Discussion The reported vulnerability of breast cancer patients diagnosed less than 1 year prior to genetic counseling and testing may be due to the recent breast cancer diagnosis and treatment [16–19]. In addition to negative psychological reactions caused by diagnosis and surgery, those due to radiotherapy [28] and chemotherapy [29,30] may play an important role. Despite this vulnerability, recently diagnosed patients seem as interested in genetic testing as patients diagnosed longer ago [31]. Julian-Reynier et al. [32] found that this understandable higher anxiety at baseline decreased after genetic counseling, even dropping to a level similar to that seen in patients diagnosed more than 1 year ago. This suggests that recently diagnosed patients, in particular, benefit from genetic counseling reducing their anxiety. Taking into account that satisfaction with genetic counseling has a positive influence on level of anxiety [32], this effect may be optimized by providing counseling that fits the specific needs of women recently diagnosed with breast cancer. There may also be specific counseling needs for affected women with a high-perceived risk for developing a second breast cancer or ovarian cancer. In described studies genetic counseling and testing did not affect patients’ perceived risk for breast cancer [20,23], as found by Bleiker et al. [33]. Butow et al. [34] concluded that genetic counseling is successful in improving the accuracy of women’s cancer risk perception in the short term, although many continue to overestimate their risk. As these personal perceptions prove resistant to standard education and counseling, affected
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women with a high perceived risk for cancer need tailored counseling. This is to make sure that an unrealistically highperceived risk is not motivating patients’ decision-making process in genetic testing and subsequent treatment. Findings by Bluman et al. [31] reveal a need to improve breast cancer patients’ basic knowledge on hereditary breast cancer and the consequences of carrying a BRCA1/2 gene mutation. Breast cancer patients from high-risk families undergoing genetic testing had a higher knowledge on genetic testing at baseline. Compared to affected women not taking part in genetic testing, these patients also demonstrated more increase in this knowledge at short-term follow up not accompanied by an increase in anxiety or depression [21]. Breast cancer patients not taking part in genetic testing probably know less about BRCA1/2 therefore we should not expect them to take the initiative in requesting counseling. By leaving the initiative to this group of patients means they will not learn more about this topic. We therefore need ways to reach affected women with a genetic risk who do not take part in genetic counseling. Bluman et al. [31] found that breast cancer patients demonstrated more interest in genetic testing when advised by their physician. For adequate referral, physicians treating breast cancer patients need to be made fully aware of the criteria of a genetic risk [35] and the process of genetic counseling and testing. In adopting an active approach, we must take into account that breast cancer patients who know little about BRCA1/2 will be unprepared for the possibility of a gene mutation and might not be psychologically well equipped to deal with genetic risk information [36]. Loader et al. [37] found index patients most prone to distress due to breast cancer risk assessment and genetic testing. This was supported by the finding that distress in women is greater if they are the first in the family to be tested for a BRCA gene mutation [38]. Accordingly, we should expect women recently diagnosed with breast cancer who are actively approached for genetic testing, and are the first in their family to be tested for a BRCA gene mutation, to be an extremely vulnerable group. There is a need for further research concerning this group. The evaluated studies did not comment on the timing of genetic testing. Patients had been diagnosed with cancer up to 32 years ago and less than 1 year before genetic testing. Weitzel et al. [14] and Schwartz et al. [15] focused on the impact of approaching breast cancer patients for genetic testing who were still in the process of making a decision about surgery. In these studies no reference was made to the possible psychological impact of genetic testing shortly after receiving a breast cancer diagnosis, while these patients may be expected to be even more psychologically vulnerable. After genetic testing, Van Roosmalen et al. [22] found more affected carriers intended to have prophylactic surgery; they valued it more highly and demonstrated a stronger preference for treatment and less uncertainty. Wood et al. [24] reported that 64% of breast cancer patients found genetic counseling and testing extremely helpful in future medical decision-making. Further research is needed to
identify vulnerable newly diagnosed breast cancer patients taking part in genetic counseling and testing in order to determine which patients need tailored counseling and to provide guidelines on how to approach them for genetic counseling and DNA testing. This review was limited to studies focusing on breast cancer patients taking part in genetic counseling and testing. Therefore, studies that report on healthy women taking part in genetic testing for BRCA1/2 with breast cancer patients as part of the study group were not included. In addition, studies focusing on breast cancer patients participating in genetic counseling and in which the process of genetic testing was not specified were excluded form this review. Five of the reviewed studies had a longitudinal design most with a short follow-up with a large variance. Of the eight emotional aspects, six were measured using a standardized tool but none of the thirteen cognitive aspects were measured using a standardized tool. The growing interest in genetic testing means there is a need for standardized tools. Overall the studies described large study groups. Three studies included a control group of unaffected women [20,22,23] and only one study made a comparison between affected women opting for genetic testing and affected women who did not [21]. Only one study provided the mean age at which the affected group was diagnosed with cancer [24]. This may play an important role considering the influence an individual’s life-stage has on the emotional impact of a cancer diagnosis [39]. In addition, there was a large variance among the studies in time between diagnosis and genetic counseling. It is necessary to study a homogenous group to provide accurate information because time since diagnoses appears to play an important role in the level of general and cancer-specific anxiety prior to and after testing. None of the studies focused on patients who declined genetic testing. In research among unaffected individuals, Lerman et al. [40] found those who declined genetic testing vulnerable. Geer et al. [41] reported patients’ concerns for health insurability, cost, emotional impact, no perceived benefit and time commitment as barriers for cancer genetic counseling. Anxiety and the anticipation of negative emotional reactions to the test result have also been identified as important reasons to decline genetic testing [42–44]. Whereas Lodder et al. [45] found that unaffected women who declined pre-symptomatic DNA testing were more likely to have thought about the decision thoroughly than deny the whole issue due to high anxiety. Questions remain on why breast cancer patients decline genetic testing and what the consequences are. Another group needing more research is that of breast cancer patients receiving an inconclusive test result. In affected women the inconclusive test result was followed by a range of emotional reactions and misinterpretation of the test result [25,26]. This is expected to be a vulnerable group since these women request counseling to gain certainty yet
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are left in uncertainty [12,46], as opposed to the carriers who said they benefited from having an end to their uncertainty [26]. Due to differences between countries we may not be able to generalize these findings to all breast cancer patients eligible for genetic counseling. The uptake for testing for hereditary breast cancer varies between countries, possibly reflecting cultural differences in attitudes towards genetic testing and related issues like health insurance and discrimination [33,40,47,48]. 4.2. Conclusions The present investigation describes eight studies focusing on the psychological aspects of genetic testing in women diagnosed with breast cancer. Most studies used a prospective design applied to a large study group. In general, genetic testing did not lead to an increase of psychological distress in breast cancer patients, although two studies reported an increase in general and cancer-specific distress after receiving a positive DNA test result. A recent breast cancer diagnosis added to the level of general and cancer-specific distress prior to genetic counseling and after receiving a DNA test result. In one study breast cancer patients’ responses to their genetic risk of future disease were not influenced by time since diagnosis. An inconclusive test result was sometimes misinterpreted and led to continuing uncertainty and a range of emotional reactions. Mutation carriers reported an end to the uncertainty playing part in their treatment decisionmaking process. Perceived risk for carrying a mutation decreased after testing, but there was no change in perceived breast cancer risk. The main reason for affected women to have a genetic test was to make relatives more alert to their own risk. Affected women found it difficult to inform family members about the DNA test result. 4.3. Practice implications Clinicians need to be aware of the possible high psychological distress in recently diagnosed breast cancer patients taking part in genetic counseling and testing. Additional counseling may be needed for patients diagnosed less than 1 year ago and patients with an unrealistic high perceived risk for a second breast cancer or ovarian cancer to manage high levels of distress and to assist these patients in their decision-making process. Further research on the psychological functioning of breast cancer patients taking part in genetic testing is needed to support more specific recommendations for this group. Important aspects to take into consideration are age upon diagnosis and time between diagnosis and genetic testing. With respect to research design, more longitudinal studies with long-term follow up are needed and a control group of affected women not referred for genetic testing should be used. More specific research recommendations pertain to the vulnerable groups identified.
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First, research must identify possible risk factors for high psychological distress in recently diagnosed breast cancer patients in order to select patients who need tailored counseling and to provide guidelines on when and how best to approach them for genetic testing. In order to optimize satisfaction with tailored counseling and its anxietyreducing effect, we need more studies focusing on the specific needs of these patients, as well as patients who have a high perceived risk for another breast cancer or ovarian cancer. Second, tools should be designed to improve basic knowledge about BRCA1/2 among breast cancer patients. Third, Among the actively approached breast cancer patients, those who decline genetic testing or receive an inconclusive test result are of particular interest for further study.
Acknowledgment We thank Jackie Senior for critically reading the manuscript.
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