Carriers of the BRCA1/2 mutation face a 50% chance that their cancer predisposition will be transmitted to their children, and individuals undergoing cancer genetic testing frequently express concern about passing on a BRCA1/2 mutation.1-3 Many patients seeking testing are of reproductive age, and are either actively engaged in family planning or will be in the near future. Preimplantation genetic diagnosis (PGD) involves the genetic analysis of embryos obtained through in vitro fertilization (IVF) and the transfer of mutation-free embryos to the mother for implantation and gestation. Recent surveys have demonstrated that there is interest by BRCA1/2 carriers in learning about PGD as a means to avoid transmitting BRCA1/2 mutations while still being able to have genetically related children.4, 5 However, the process can be arduous and expensive, at times requiring multiple cycles of fertility medications and implantation attempts to achieve a successful pregnancy. Furthermore, consideration of PGD for patients who carry BRCA1/2 mutations introduces the possibility of medically invasive procedures to those who otherwise might be able to conceive normally, in a population that is already being asked to weigh multiple risk management options (eg, surgery or intensive surveillance).6
Currently, professional guidelines regarding the discussion of PGD with patients carrying the BRCA mutation during cancer genetic counseling call for providing “…as much information as possible while acting in an ethical context that minimizes harm to clients and their families.”7 The challenge for health care providers is how to incorporate information regarding PGD, which is highly technical, into sessions that are already pressed for time due to the complex, probabilistic, and emotionally charged nature of genetic risk information and risk management.8, 9 Furthermore, several studies have shown that PGD can trigger a host of psychosocial and ethical issues, and opinions concerning the acceptability of PGD for adult-onset cancer syndromes with incomplete penetrance vary widely among both patients and providers.4, 5, 10, 11 With such variability, guidance is needed to avoid inadvertently harming patients in the process of informing them of their options.
We elicited patient preferences regarding when and how they would want to learn about PGD as part of a larger qualitative study of attitudes concerning PGD and prenatal diagnosis (PND) among BRCA1/2 mutation carriers of reproductive age who had previously undergone genetic counseling and testing for breast/ovarian cancer risk. For this report, patients were asked to reflect on their counseling experience and how they would have wanted to integrate PGD information into the counseling process.
MATERIALS AND METHODS
For this Institutional Review Board-approved study, 98 BRCA1/2 mutation carriers of reproductive age (aged <43 years for women and age <50 years for men) and capacity (no history of hysterectomy or bilateral oophorectomy in females) who completed genetic counseling and testing at Memorial Sloan-Kettering Cancer Center (MSKCC) were invited by letter for a 2-hour, in-person interview regarding attitudes about PGD and PND for patients with breast/ovarian cancer risk. Approximately 34% of the carriers invited accepted, 45% did not respond, and 21% declined. The majority of those declining cited being too busy and/or scheduling conflicts; a few (5 individuals) expressed that cancer risk and/or PGD were too emotionally difficult for them to discuss. One woman consented and began study participation, but her interview was not transcribed or included in this analysis after signs of psychiatric impairment emerged during her interview.
Participants were mostly female (88%), white (91%), married/partnered (73%), highly educated (42% with >16 years of education), and of high socioeconomic status (42% earning >$200,000 per year). Female participants were younger (mean age, 33.24 years [range, 21 years-41 years]) than the males (mean age, 37.5 years [range, 26 years-48 years]). Approximately one-half of the participants (51.5%) had children, and approximately one-quarter (24.2%) reported their childbearing was complete.
Interviews were completed by doctoral-level, licensed mental health professionals experienced with patients with hereditary cancer risk. Upon providing informed consent, patients completed a demographic questionnaire and an assessment of prior knowledge regarding PGD and PND. Patients varied with regard to time since initial genetic counseling and whether PGD had been discussed during genetic counseling. Therefore, interviewers presented a standardized tutorial reviewing risk and inheritance patterns associated with BRCA1/2 mutations, defining PGD and PND, and describing the procedures and associated considerations (eg, cost, availability) of each so that all participants were exposed to basic concepts relevant to PGD and PND before the interview. To minimize possible order effects, participants randomly viewed either PGD information first or PND. The tutorial was developed in collaboration with a doctoral-level genetic counselor and reproductive endocrinologist and reviewed by MSKCC genetic counselors and physicians. After the tutorial, interviewers confirmed that participants understood the information via a brief assessment. Interview questions covered personal and family histories of cancer, risk management decisions, perceived benefits and drawbacks of PGD and PND, ethical and emotional considerations related to PGD and PND, and opinions regarding incorporating information about PGD and PND into cancer genetic counseling. Thus, opinions elicited from participants concerning incorporating PGD into cancer genetic counseling occurred as part of a wide-ranging discussion of attitudes, and within the context of the participant's experience of the impact of her or his mutation carrier status.
Thematic analysis was used to code and analyze data regarding patient preferences because this question represented an a priori goal of the current study.12 Thematic analysis is “a method for identifying, analyzing, and reporting patterns (themes) within data.”12 The research team reviewed an initial subset of transcripts to generate a preliminary code book of themes articulated by participants. Two independent raters then coded each transcript, with coding discrepancies resolved through discussion by the coding team. Atlas.ti qualitative data analysis software was used to organize and sort the data (ATLAS.ti Scientific Software Development GmbH, Berlin, Germany). The current study focused on a subset of the themes identified, specifically those that were relevant to a participant's views concerning how information regarding PGD should be incorporated into genetic counseling. In addition, counseling-related themes are presented only for PGD and not for PND, because the acceptability and practice of PND for adult-onset cancer syndromes are less well-established.8
Main Theme: The Value and Burden of PGD Information
Participants nearly universally agreed that PGD should be addressed during cancer genetic counseling, regardless of whether they would avail themselves of it.
“I think I'd want to know that I had that option, even if I wouldn't want to use it.”(052)
The core dilemma revealed in the interviews was that participants wanted as much information as possible regarding BRCA-related options, including PGD, but at the same time many believed that they received too much. For example, one participant stated:
“I'm somebody who likes to have information. I'm not scared by information. I find information useful and comforting, no matter what the information is.” (026)
Later, however, the same woman declared:
“I got way too much information at the first session!!” (026; participant's emphasis)
Participants also recognized that not everyone would be equally receptive to information regarding PGD:
“…I think for some people it (PGD) is going to be a big relief. For others, it would actually pile more on… (034)
Thus, although participants were near unanimity in favor of equal access to information, it was clear that a one-sized approach would not fit all. To navigate this dilemma, we identified 4 themes that reflected patient preferences regarding the presentation of PGD information.
Theme 1: Preferred Level of Detail
The majority of participants did not favor a detailed presentation on PGD during genetic counseling. Rather, they suggested that providers touch upon PGD as an option that could be discussed if the person was interested and/or at a future visit.
“…put it out there and just say, ‘I don't know if this is right for you, but know that it's an option.’” (002)
“Maybe just mention it quickly but not to really go into depth unless a person wants to know more…” (092)
Patients expressed concern about “overload” if too much detailed information concerning PGD was added to their genetic counseling sessions. For some, the feeling of being overloaded reflected the volume of information covered during the sessions:
“That appointment is a couple hours long, and it is information overload, even just with what they give you.”(006)
For others, “overload” suggested a psychological state in which they were negatively affected by receiving too much information. Negative impacts included distress, conflicting priorities, and an inability to absorb new information. Several participants used metaphors referring to the head or mind to signify a process of figuring what risk information meant for them personally, and expressed that feeling emotionally overwhelmed interfered with that process:
“I think it would have been too much information, because it's hard enough to wrap your head around how that [risk information] impacts you, let alone thinking how's that going to impact my possibly unconceived child?” (072; emphasis added)
“Initially…all I cared about was what it [mutation] was and the percent chance I could pass it on and then the percent chance it increased my breast cancer coming back…once I figured that out and was able to process everything and do everything else I was doing at that time…then your mind can be open for more information.” (006; emphasis added)
“The genetic counselors need to consider what's the right amount of information to give at that visit so that the real issues of being positive and what that means for your life are–because it's already so confusing and it's so emotional, it's hard to get your head around it. Then to get a barrage of other details about PGD could be overwhelming.” (065; emphasis added)
They acknowledged tuning out information when they felt overwhelmed. At times, patients described seemingly voluntary strategies:
“It wasn't the most effective time to hear it [information about PGD]…I let it go in one ear and out the other.” (041)
Other times, tuning out appeared to be an involuntary response:
“…when they [patients] go [to genetic counseling] and they're in the initial stages, they go into a fog after 5 minutes…”(051)
Some participants were concerned that having information about PGD created pressure to make a decision and act on it, perhaps before they were ready. That pressure, coupled with any emotional distress they were already experiencing about learning their risk status, led some to express fears that patients still in the early phases of coping with their risk status would make impulsive decisions about PGD:
“…you also have to worry about people's mental states at that point, too, because a lot of the time, they are just diagnosed, or the sister of someone just diagnosed, or something, so I believe like people are a lot more emotional and maybe not as logical in their decision-making.” (006)
“If you want to make sales on IVF, tell them then [in counseling session before testing] because they're scared and they're going to go do it, and they're going to make impulsive decisions.” (010)
Ultimately, most participants were in favor of providing at least a minimal amount of information concerning PGD during patient sessions because, even with drawbacks, not to be aware of PGD as an option would be worse:
“I would have been so upset if I'd found about it after I'd already made my planning decisions.” (034)
Theme 2. Preferred Mode of Transmission
Many participants suggested that they be given a pamphlet about PGD that they could review on their own time.
“Since this [PGD information] may all float over their heads that might be a good thing to give them in a handout to take home with them and peruse later.” (052)
“If you want to pick it up you can, if you don't you don't. It's more like if the headline interests you, you're going to pick it up …” (080)
Having the information written down would make it easier for patients who wanted to do their own research on the Internet but were unfamiliar with the terminology:
“There was no information handed to me…Because I still think I don't even know who I'd Google, I don't even know any of the terms…” (082)
However, a pamphlet would need to stand out from other written materials that are handed out at genetic counseling sessions, such as risk management summaries and referral information:
“I [was overwhelmed]…by this packet of information I got in the beginning with these dozens of doctors-most of whom have nothing to do with what I needed.” (026)
“…printouts of basic information and some pamphlet[s]… but if you gave me too much I probably wouldn't have read it anyway.” (080)
Others suggested that a follow-up session focused on PGD be available for those who were interested. Perceived benefits of this approach were to allow assessment of how the patient was handling his or her results, and to allow time to digest the information.
“Definitely the better thing to do [than to discuss PGD at the results session] would have been to have a follow-up appointment in 2 weeks to make sure that I was functioning, and then to find out if I…was ready to discuss at that point.” (034)
However, other participants doubted that patients would attend additional sessions:
“You have to give it [information] all at once…nobody's coming back for more.” (051)
Theme 3. Preferred Provider of Information
Participants expressed a variety of opinions about from whom they would prefer to hear about PGD. They expected that genetic counselors would be able to provide information if they wanted to discuss it:
“…the genetic counselors definitely should be well-versed with this information…” (074)
However, the fact that consideration of PGD opens up sensitive questions in several realms, from ethics to personal and family goals, led some to emphasize that they would want to talk with a physician whom they already knew:
“A lot of this does touch on a lot of personal and very ethical issues, maybe it would be easier coming from someone that you believe like you have a relationship with.” (041)
“At least my oncologist has a longer-standing relationship with me. The genetic counselor I had only met for about half an hour the day they took the blood.” (013)
Some preferred their obstetrician, with whom they had already discussed other important medical decisions, and who were perceived as experts in childbearing issues:
“I mean, they are the ones, you know, the trusted doctors that are delivering your babies, and they could be a great support of it.” (025; participant's emphasis)
“I think [information about PGD] coming from a genetic counselor of course, but I see my OB/GYN annually, so I believe like if I were to talk about having a child that I would probably go to her first.” (021)
However, others preferred their primary care provider to initiate the discussion earlier in the family planning process:
“I think it should start with your [primary] medical physician, because once you're pregnant it's too late.” (074)
One recurrent suggestion was that the genetic counselor provide introductory information, but that a more extended discussion take place with the physician.
“So genetic counseling, number one, to give you the idea, so then you can go and talk to your physician about it.” (025)
Patients recognized that not all physicians were equally versed in the details of PGD, and that a pamphlet could supplement physician knowledge:
“If the doctors are not comfortable talking about it, or they don't have enough information about it that they can speak on it professionally, the pamphlets are there.” (074)
Theme 4: Preferred Timing for the Receipt of Information
Participants expressed a variety of opinions about when PGD should be discussed. Some participants believed that learning about PGD before knowing their test result would not be meaningful:
“…Let's face it, it's not an issue if they're not positive.” (056)
Furthermore, learning that the future might hold additional medical procedures (beyond those a person had already undergone for cancer treatment and/or were considering for risk management) was also viewed as stressful for some:
“I didn't want to know until after I had my results, because what would be the point of getting all nervous about all these procedures before I knew for sure that I needed it?” (007)
However, others saw a benefit in mentioning PGD at the time of the initial pretest visit:
“I think it's important to say it then [at the initial session] because then you believe like there's hope for the future, as opposed to just stagnating on your own genetics.” (051)
Some participants, particularly younger ones, expressed that they wanted to put off learning about PGD because they wanted to focus on their immediate risk management needs, rather than on reproductive issues that might not arise for several years:
“There was a lot to sort out all at once for us; who was I going to see for surveillance…and then having this other thing to deal with that was a little more future oriented…” (065)
“I was just more concerned about me at that point developing cancer than my children, at 19.” (087)
Last, some believed that the information should be discussed only with those who were actively trying to conceive, when it would be mostly timely:
“I think it's a good idea to be offering that to people as certainly part and parcel if you're already having the IVF and you're already screening the embryos for one thing or another…” (028)
Others saw a benefit in letting everyone know about the availability of information about PGD, regardless of their childbearing status:
“But someone in their 60s getting a BRCA diagnosis you may spend a little less time or just give her the information for her daughter.” (091)
In this qualitative study, a majority of BRCA1/2 mutation carriers reflecting on their genetic counseling experience expressed that although they wanted to be briefly informed of the availability of PGD information, they wanted the option of deferring a more detailed presentation if they were already feeling overwhelmed or perceived that PGD was not immediately relevant to their medical and/or childbearing plans. PGD information was generally viewed as valuable, but also potentially taxing of patients' psychological resources because it requires a mastery of medical technicalities and introduces a set of ethically and emotionally charged decisions to be made on top of those patients were already making regarding testing and risk management.6, 13 Participants offered a diversity of opinions regarding with whom they would prefer to discuss PGD and the timing of such a discussion, namely whether it should occur before genetic testing for cancer risk or after receipt of a positive test result. Although prior studies have addressed patient attitudes regarding PGD for hereditary cancer risk, to our knowledge the current study is the first to specifically address patient preferences about receiving PGD information for BRCA1/2 mutations.
Some participants described feelings of “information overload” consistent with prior reports in BRCA1/2 carriers,14, 15 and in cancer patients more broadly.16, 17 Furthermore, some participants appeared to limit their exposure to new information through cognitive avoidance, either purposefully (“in one ear and out the other”) or in an involuntary “fog-like” state, as a way to cope with emotional stress during genetic counseling. Indeed, some patients declined study participation, citing their high levels of distress. Research concerning stress and coping in a wide variety of domains has shown that avoidance increases under stress.18 Studies of cancer genetic counseling patients also have demonstrated that mean levels of distress tend to be highest immediately before testing and after the receipt of genetic test results,19 which may be when patients are most likely to believe they are overwhelmed. Paradoxically, these are also the times when it is most convenient for clinicians to deliver information about PGD and, for at least some patients, when information about PGD might be relevant to their testing and risk management decisions. Some participants reported that they were better able to process BRCA-related information after having had time for reflection, which dovetails with studies indicating that for most people, distress levels after testing decrease over time.19, 20 Therefore, for at least some patients, preferences concerning the timing and volume of PGD information appear to implicitly reflect their current level of coping with the genetic testing process.
Cognitive avoidance may be effective in the short run for coping with feeling distressed and overwhelmed.21 However, although tuning out overwhelming information may help the patient in the moment, it is not an effective use of a provider's time, and may undermine patient satisfaction with the encounter. Furthermore, according to social-cognitive processing theory, avoidance can inhibit an individuals' ability to integrate information with core beliefs about self, values, and goals,22 a process that would appear to be important when making a decision with the ethical and emotional complexity of PGD. The question then becomes how to efficiently facilitate cognitive processing when decisions will yield the most clinical benefit. A recent study in genetic counseling communication found that counselors who engaged in the facilitation of emotional expression not only increased their clients' expression of distress, but also of words indicating cognitive processing.23 Future qualitative research can query patients specifically about the experience of information overload, generating a phenomenology of voluntary and involuntary coping that can be linked to outcomes such as distress, decision quality, and decision satisfaction. Such findings could be synthesized with provider-patient communication research focusing on verbal and nonverbal cues signaling information overload to generate solutions that resolve the patient-provider impasse that such overloading can produce.24 In the interim, the suggested approach by the current study participants to briefly touch on the availability of PGD information might be viewed as an invitation for providers to openly address information overload and negotiate the timing of PGD discussions via an information plan.
It is interesting to note that in this highly educated and presumably computer-savvy group, there were numerous spontaneous mentions of wanting a pamphlet concerning PGD, but none of referring patients to the Internet for more information. Although no participant specifically commented on this, it may be that receiving a brief, tangible, written resource from the provider, rather than being sent to dive back into the flood of online information, would be perceived as being more responsive to the patient's implicit need to control their rate of exposure to PGD information. A pamphlet could also function as a neutral source of information for discussion, so that patients would not be overly dependent on the attitude or knowledge level of any given provider regarding PGD.
Although the interview focused on the integration of PGD information into genetic counseling, some participants expressed interest in discussing PGD with physicians with whom they have had an ongoing, trusting relationship, such as a primary care provider, oncologist, or obstetrician/gynecologist. It appeared that participants looked to genetic counselors to inform them of the availability of PGD information, discuss it in more detail if desired (eg, how it would affect the patient's testing decision), and provide a pamphlet. The finding that some patients would want to discuss PGD with physicians underscores the need for continuing medical education about the technical aspects and risks of PGD, as well as the breadth of psychological issues. Surveys have indicated that physicians are challenged to keep up with the rapid pace of genetic discovery and its clinical implications,25, 26 but can improve patient knowledge with educational interventions.26
The results of the current study may not generalize to all cancer genetic patients because in this study, all participants had received cancer risk counseling from a genetic counselor, with an attending physician joining the session toward the end. Many participants remarked on the level of technical detail in their counseling sessions, and this may have influenced their reaction to the introduction of another large chunk of medical information. Patients who have not received the full measure of genetic counseling that is currently recommended by several professional organizations (eg, the American Society of Clinical Oncology, National Society of Genetic Counselors, American Society of Human Genetics, and American Congress of Obstetricians and Gynecologists,)7, 27-31 may have different preferences regarding the presentation of information regarding PGD. In addition, we presented standardized information concerning PGD as part of the research design so that we could focus the discussion on the study questions. However, in practice, patients who have no prior knowledge of PGD and who do not receive a standardized presentation may have alternate preferences for PGD discussions. Similarly, we included women who had already completed childbearing to explore their reflections on the genetic counseling process. One participant discussed the potential benefit of older women learning about PGD for their daughters; patients in this situation may have information preferences that we did not fully explore. The group of respondents in the current study (34% of those to whom invitations were sent) may not fully represent the experience and preferences of all patients undergoing BRCA1/2 genetic counseling, particularly those who declined to participate because the topic was distressing to them.
Males are underrepresented in the current study sample. Male carriers of the BRCA1/2 mutation do not face the number or degree of personal risks that female carriers face, and therefore may be less susceptible to information overload. However, they have other emotional challenges such as helplessness and guilt about possibly passing a mutation onto their children.32 Furthermore, their attitudes toward PGD may be shaped by the fact that they would not undergo the IVF procedure.33 Therefore, they may have different needs regarding the timing and content of PGD-related discussions that merit further study. In addition, noncarrier partners were not interviewed for this study, but patients indirectly reported that a partner's attitude was influential. Future work should explore the informational needs of partners as well, particularly with regard to the management of disagreements about pursuing PGD.
Participants in the current study preferred options that would help them control the flow of information about PGD to avoid feeling overwhelmed. This dynamic presents a challenge to providers to balance their mandate to provide information about BRCA-related options with sensitivity to individual differences in a patient's ability to process information. Based on suggestions by our participants, providers can briefly describe the potential benefits of learning about PGD, watching for cues indicating that a patient is having difficulty absorbing information, such as inattention or requests to repeat information. They can then create an “information plan” with patients regarding when and how they will learn more about PGD if desired. Further research focusing on information overload occurring during cancer risk consultations can inform efforts to enhance a provider's ability to identify and respond to those patients who are feeling overwhelmed.
Based on the results of the current study, it appears that the challenge of incorporating information regarding assisted reproductive options into cancer genetic counseling is not merely one of adding a large chunk of information to the details that already comprise the standard of preventive medical care. Rather, the health care provider is faced with the challenge of actively assisting patients as they process information regarding reproductive choices on both a cognitive and emotional level. An emerging goal of preventive oncologic practice will be to help families affected by cancer to balance individual goals and coping abilities to facilitate optimal decision-making about PGD and other means of assisted reproduction as part of the management of their hereditary cancer risk.
We thank Mark Robson, MD; Emily Glogowski, MS; Beth Siegel, MS; Sherry Boyar, MS; Angela Arnold, MS; and Megan Harlan, MS, for their valuable feedback on the educational tutorial. We also thank Maya Doyle, MA, for data coding; Jessica Joseph, BA, for article preparation; and Christopher S. Webster and David Gregory for administrative assistance. Professional transcription was provided in compliance with Health Insurance Portability and Accountability Act (HIPAA) regulations by Richard Fisher (RA Fisher Ink LLC).
Note Added in Proof
Supported in part by funding from the National Institutes of Health, including the National Human Genome Research Institute (R03 HG0004528; PI: L. Rubin), the National Cancer Institute (K07 CA109236 [PI: K. Hurley] and T32 CA009461-22 [PI: J. Ostroff]), the Kate and Robert Niehaus Clinical Cancer Genetics Initiative, the Sharon Levine Corzine Fund for Cancer Research, and the Charles Krasne Research Fund.
CONFLICT OF INTEREST DISCLOSURES
The authors made no disclosures.