Information Topics of Greatest Interest for Return of Genome Sequencing Results among Women Diagnosed with Breast Cancer at a Young Age

Abstract

We investigated what information women diagnosed with breast cancer at a young age would want to learn when genome sequencing results are returned. We conducted 60 semi-structured interviews with women diagnosed with breast cancer at age 40 or younger. We examined what specific information participants would want to learn across result types and for each type of result, as well as how much information they would want. Genome sequencing was not offered to participants as part of the study. Two coders independently coded interview transcripts; analysis was conducted using NVivo10. Across result types, participants wanted to learn about health implications, risk and prevalence in quantitative terms, causes of variants, and causes of diseases. Participants wanted to learn actionable information for variants affecting risk of preventable or treatable disease, medication response, and carrier status. The amount of desired information differed for variants affecting risk of unpreventable or untreatable disease, with uncertain significance, and not health-related. Women diagnosed with breast cancer at a young age recognize the value of genome sequencing results in identifying potential causes and effective treatments and expressed interest in using the information to help relatives and to further understand their other health risks. Our findings can inform the development of effective feedback strategies for genome sequencing that meet patients’ information needs and preferences.

Introduction

Medical and technological advances in genetics and genomics may improve patient care by providing individual genomic information for patients (Biesecker and Green 2014; Manolio et al. 2013; Mardis 2008; Pasche and Absher 2011). As the availability of these technologies expands, the clinical use of genome sequencing is increasing (Jamal et al. 2013; Manolio et al. 2013). While genome sequencing may confer benefits, there are several characteristics of the information to consider when returning results to patients. Notable is the vast amount of information that will likely be generated by sequencing, including results that are both related to the patient’s diagnosis or disease risk and unrelated secondary findings (Bredenoord et al. 2011; McGuire and Lupski 2010; Sharp 2011). For instance, genome sequencing may identify information that has unknown significance, is not clinically actionable, or could have implications for the health of a patient’s family members (Bredenoord et al. 2011; Caulfield et al. 2008; Sharp 2011). Therefore, it is critical to consider two communication issues related to returning genome sequencing results to patients: what results to return to patients, as well as what information patients need and want to know about each type of result.

Previous recent work has addressed the former issue. The American College of Medical Genetics and Genomics (ACMG) has recommended what results to return after clinical sequencing (Green et al. 2013). In addition, prior research has shown that patients want to receive individual results from genome sequencing (Kaphingst et al. 2016; Matsui et al. 2008; Murphy et al. 2008; O’Daniel and Haga 2011), although findings regarding what specific types of results patients want returned are mixed (Hitch et al. 2014; Kaphingst et al. 2016; Leventhal et al. 2013; Wright et al. 2014; Yu et al. 2014). However, much less is known about what information patients would like to learn about each genome sequencing result when it is returned (Bredenoord et al. 2011; Dressler 2009a, b). Major trends toward patient-centered care highlight the importance of allowing individual patient preferences, needs, and values to guide clinical decision-making (Institute of Medicine 2001). In order to meet a standard of patient-centered care, patients’ information needs and preferences are therefore critical to understand in order to develop effective strategies for feedback of results from genome sequencing (Schmidlen et al. 2014).

Understanding what information individuals would like to receive about the genome sequencing results that are returned to them is particularly important for young breast cancer patients, a population that may receive substantial benefits from the early application of genome sequencing. Breast cancer patients who carry inherited germline mutations contributing to breast cancer risk, such as BRCA1 or BRCA2, are at increased risk for a second primary breast cancer and other cancers (Mavaddat et al. 2013); patients who are diagnosed at age 40 or younger are more likely to carry such gene mutations (Anders et al. 2008; Bonadona et al. 2005; Golshan et al. 2006). For carriers of BRCA1 or BRCA2, genome sequencing can be beneficial for surveillance and surgical decisions (Heemskerk-Gerritsen et al. 2015; Ingham et al. 2013; Riedl et al. 2014; Sieh et al. 2014; Trujillano et al. 2015). Moreover, even for BRCA1 or BRCA2-negative patients, genome sequencing may be beneficial in identifying other genes, such as PALB2, CHEK2, and ATM, that may confer an increased risk of familial breast cancer (Cybulski et al. 2011; Desmond et al. 2015; Janatova et al. 2013; Renwick et al. 2006). Genome sequencing can be used to identify and choose targeted therapeutic agents for some cancer patients (Ellis et al. 2012; Yauch and Settleman 2012; Zardavas et al. 2013). Continuing research in gene discovery that uses genome sequencing technologies is also critical for this patient population, as young breast cancer patients have lower survival rates (Anders et al. 2008, 2009; Assi et al. 2013; Fredholm et al. 2009) and an increased incidence of stage IV disease at initial diagnosis among women below age 40 diagnosed with breast cancer compared to older women (Johnson et al. 2013). Therefore, for various research or clinical reasons young women diagnosed with breast cancer may receive results generated by genome sequencing, but we have little understanding of what these patients would like to know about each result (Ellis et al. 2012; Yauch and Settleman 2012; Zardavas et al. 2013). We therefore investigated what information women diagnosed with breast cancer at age 40 or younger would want to learn if individual genome sequencing results were returned to them. These findings can guide clinicians, researchers, and genetic counselors in prioritizing key topics when developing feedback strategies for returning genome sequencing results to these patients.

Methods

Recruitment

We recruited a purposive sample of 60 adult women from an existing nationwide cohort of women diagnosed with breast cancer at age 40 or younger, the Young Women’s Breast Cancer Program (YWBCP) (Kaphingst et al. 2016). YWBCP participants in the St. Louis region were contacted by e-mail, letter, and e-newsletter. The recruitment materials stated the purpose of the study (i.e., to learn more about how best to return genetic information to women who have been diagnosed with breast cancer at a young age) and expressed interest in participation from women with differing viewpoints, regardless of prior experience with genetic testing. Recruitment was stratified into four subgroups by family history of breast cancer, having received genetic testing, and BRCA1/2 mutation status, described in detail elsewhere (Kaphingst et al. 2016). Recruitment was stratified so that we could explore differences among the participant subgroups. Family history of breast cancer was scored by an experienced genetic counselor and classified as strong (i.e., one 1st or 2nd-degree relative diagnosed younger than age 50; two relatives diagnosed at any age; or male relative diagnosed); moderate (i.e., one 1st or 2nd⁻ degree relative diagnosed at age 50 or older); or no history (i.e., no 1st or 2nd-degree relatives diagnosed).

Participant Characteristics

All participants in the study were recruited into the YWBCP because they had been diagnosed with breast cancer at age 40 or younger; however, participants’ time since diagnosis at the interview varied widely. Participants’ ages at the time of interview ranged from 33 to 64 years; the mean age at breast cancer diagnosis was 37 years (range: 27–40). The majority of participants were Caucasian (97 %) and had a college degree or higher (75 %). About 73 % of participants had received prior genetic testing for BRCA1/2; of these, 32 % carried a deleterious mutation in at least one of the genes.

Interview Procedures

We conducted qualitative, semi-structured, in-person interviews. We first developed an interview guide based on existing literature, which was refined based on initial interviews. The interviews began with an introduction to the topic of genome sequencing and a few general questions about attitudes toward genome sequencing. Then, open-ended questions assessed participants’ preferences regarding six different possible types of individual results from genome sequencing, variants that: related to risk of a preventable or treatable disease; risk of an unpreventable or untreatable disease; affected treatment response; uncertain significance (VUS); carrier status; and no health meaning (i.e., ancestry, physical traits). Each type of result was described with examples before the questions. In this analysis, we investigated what information topics participants wanted to learn overall if genome sequencing results were returned to them, as well as what topics they would like to learn about each type of result (Table 1). We first asked broad, unprompted questions about what information participants wanted to learn about a particular type of result. We then further probed on whether they would want to learn specific types of information using prompts (e.g., how much the gene variant affects disease risk, how the gene works in the body, how common the gene variation is in the U.S. population). We also asked how much information participants would want about these topics (e.g., how interested she would be in learning information about a gene variation that increases the risk of developing a disease that cannot be prevented or treated). The full interview guide is available as a supplement to Kaphingst et al. (2016) or from the authors. Genome sequencing was not offered to participants as part of the study.

Table 1.

Sample questions in the interview guide

Question type	Sample questions
General questions about genome sequencing	If researchers sequenced your genes and were able to find out what variations you carry in your genes, what would you hope to learn? If your genes had been sequenced at the time of your breast cancer diagnosis, how might you have used the results?
Risk of preventable or treatable disease	If you had a gene variation that increases your risk of developing a disease that may be able to be prevented or treated, what would you want to learn about that variation? -Would you be interested in learning about how much the gene variation affects your disease risk?
Pharmacogenomic	If the gene variation affected how you respond to a treatment commonly used for breast cancer, how would you describe your interest in this information? -How would your interest in this type of information be different if it related to treatment for a disease other than cancer?
Uncertain significance	Would you be interested in learning that a large number of your genes have a variation with an uncertain meaning? Would you like to learn how common the gene variation is in the U.S. population?
Risk of unpreventable or untreatable disease	If you discovered that you carry a gene variation related to your risk of developing a cancer that we currently know little about preventing, such as pancreatic cancer, how would you describe your interest in learning this information?
Carrier status	How interested would you be in learning this type of information about a gene variation that does not affect your health but might affect the health of your relatives? -Would you want your biological family members, like your children or brothers and sisters, to be able to find out about this information?
Non-health meaning	How would you compare what you would want to learn about this variation to what you would want to learn about the other types of information that we have discussed?
Overall thoughts about different types of information	Of the different types of information that we’ve discussed, what type of information would be of greatest interest to you?

Two trained master’s-level research assistants conducted the interviews, which lasted about 90 min. Interviewers could change the order of the questions in order to follow the flow of the participants’ comments and used follow-up questions to elicit more details. All interviews were digitally recorded and transcribed verbatim by a professional transcriptionist. Each participant received a $50 gift card incentive. The university institutional review board reviewed and approved this study.

Data Analysis

We conducted a directed thematic analysis of the interview data (Hsieh and Shannon 2005). Initial thematic domains and a preliminary codebook were developed based on prior literature and the interview guide. The codebook was then revised by the research team to add inductively derived codes and thematic domains through an iterative, ongoing process that began after the first interviews. After the codebook was complete, all data were coded with the final codes. Two trained coders who had not conducted the interviews independently coded all transcripts using NVivo10. Following this, we used a team-based approach in which coders discussed discrepancies amongst themselves and with the research team; analysis was based on consensus codes (Guba and Lincoln 1994). Memos summarizing each code were created and used to identify core themes. Although we investigated whether themes differed across the participant subgroups, we did not identify key differences. We therefore present the results overall below.

Results

Information Topics of Greatest Interest Across Result Types

Three major themes emerged across result types regarding information topics that participants wanted to learn if sequencing results were returned to them (Table 2). Participants most wanted to learn about the health implications of the variant. More specifically, participants were interested in learning about the potential long-term impact and health outcomes for themselves related to the variant: “I’d wanna learn… What does this mean for my health? What does it mean for daily life? I mean it’s one of those things that you have to say, am I gonna lose ability to do something because of this unspecific gene?” [Participant 30] Participants also expressed interest in learning about health implications for relatives: “I would want to learn what effect that would have on [my family members’] health and their future health… the possibilities not just affecting my children’s health or my siblings’ health but what they would pass on to their family.” [Participant 5].

Table 2.

Information topics of greatest interest for return of sequencing results (n = 60)

Major Theme 1: Health implications of the variant
Information topic	Representative quotes
Long-term or health impacts, for self and for family members	“[I would want to learn] anything that would have implications for [my] care, or implications for my family.” [Participant 14] “I’d want to know just what effect those results would have on my life and health.”[Participant 21] “I would want to know useful information that could impact my health… and the health of others around me.” [Participant 16]
Major Theme 2: Risk of the variant and prevalence of the variant
Information topic	Representative quotes
Specific statistics about level of risk, for self and for family members	“I guess the most important things to me would be learning whether there’s any likelihood of either me or my children developing a condition… health related things [are] mostly what I’d be interested in.” [Participant 22] “[I would want to learn] the likelihood that I am going to get this, the percentage.” [Participant 34]
Prevalence of the variant in the general population and among breast cancer patients	“I’d like to know how prevalent is this [variant]? Is this a common variation?” [Participant 51] “I would hope to learn… if it’s a common mutation that’s causing mine that they found in other breast cancers.” [Participant 26]
Major Theme 3: Causes of the variant and if it causes diseases
Information topic	Representative quotes
Reasons for carrying the variant, especially for family members	“I would be interested to know if there was a cause for that variation. If that were… just a natural mutation or if there was an environmental impact that caused the variation.” [Participant 5] “I guess, probably how it started, and was it something I was born with, is it something that my family members could have, and what happened in my life to make it progress.” [Participant 57]
Whether the variant causes diseases, including breast cancer	“If there were any variations or mutations that were significant to the development of cancer.” [Participant 45] “[I would want to learn] if it is the variation that causes disease… how common that variation causes the disease.” [Participant 48]

Participants were also interested in learning about both the risk conferred by the variant and the prevalence of the variant in quantitative terms. In particular, participants wanted to learn specific statistics about their personal level of risk: “Definitely tell me some sort of percentage or scale. You know, don’t [say], you just have this or propensity for this… give me my risk, the chances, of you know, am I actually developing this problem.” [Participant 11] Participants were also interested in learning the prevalence of the variant in the general population: “Well it’d be numbers, statistics, how many other people had that variation…” [Participant 33], as well as the prevalence of the variant specifically among breast cancer patients: “You could kind of see if… there is a lot of people who have had breast cancer with that [mutation]. Might give you just a little bit more comfort in what’s going on.” [Participant 48] In addition, participants also wanted to know how likely it was that family members would carry the variant: “I’d wanna know what the risks are… if you have the gene how likely you are to pass it on… if you’re married and you’re gonna have children, if the other person has to have the gene, you know, just the impact of it.” [Participant 21].

Third, participants wanted to learn both about causes of the variant and whether the variant causes diseases. Participants stated that they would want to know why they carried the variant; for instance, whether the variant was a spontaneous mutation due to chance, passed on from their parents or other family members, congenital, or environmentally or behaviorally caused: “What caused it, was it environmental… was it something I was born with… You know, did something in my world change it… or was it something I was doing.” [Participant 17] For some participants, knowing the cause of the variation was especially important for their children and future generations: “If they figure out what causes variations, it’d be nice to know for your children. It’s like I did this and that caused that variation so don’t do that.” [Participant 26] Additionally, participants wanted to know if the variant causes diseases: “What [the variants] cause, potentially… whether it’s cancer or some other kind of disease.” [Participant 32] Some related it specifically to their breast cancer experience: “I would hope to learn how I got my cancer and if the information could… help someone else.” [Participant 20].

Information Topics of Greatest Interest for Each Type of Variant

We also examined what information topics were of greatest interest to participants when each type of sequencing result was returned (Table 3). For variants that increase risk of a disease that can be prevented or treated, participants most wanted to learn what they could do to reduce their risk, prevent disease onset, or treat the disease. In particular, participants wanted to know what specific action steps they could take for prevention and treatment.

Table 3.

Information topics of greatest interest by variant type (n = 60)

Variant type	Information topics	Representative quotes
Risk of preventable or treatable disease	How to lower risk or prevent disease onset	“I would just want to learn the steps that need to be taken–so that we can try to prevent it, before a disease occurs.” [Participant 1]
Pharmacogenomic	How to use information to determine best treatment for themselves	“Probably more treatment options around that variation… understanding… what that specifically means to me–how it could be customized to me.” [Participant 60] “I would wanna know how well I would respond… to the treatment, if I would be a good candidate for the treatment and then what the potential side effects would be, if I’m at greater risk for side effects.” [Participant 45]
Uncertain significance	Research on the meaning of the variation, both now and in the future	“Where the research stood. What they think it might be tied to, where they are in terms of the research” [Participant 14] “I’d want to learn what the meaning was. And I understand that… that’s a future conversation.” [Participant 16]
Risk of unpreventable or untreatable disease	Likelihood of getting the disease	“How common it is, and the statistical likelihood that having the gene means that you will develop the disorder… I’d wanna know what percentage chance that was.” [Participant 13]
Carrier status	How their relatives would be affected, to share with family members	“I would want to learn what effect that would have on their health and their future health… [and] what they would pass on their family.” [Participant 5] “Enough information to be able to communicate it effectively and understandably to them.” [Participant 28]
Non-health meaning	Meaning for ancestry	“It would be interesting to know where my ancestors originally came from, you know, just to find out more history of my family.” [Participant 17]

For variants that affect response to medication, participants wanted to know how the variant affects their treatment response and how to apply the information to their own situation. In particular, some felt this information would be helpful in discussing treatment options with their doctors and determining the best course of action: “I would want to have that information to give to my doctors so that they would know which medications to use, which [will] have the better response.” [Participant 29].

For VUS, participants most wanted to learn about the state of research related to uncovering the meaning of the variant. Because most participants understood that the meaning of the variant was currently uncertain, they wanted to learn about future research: “Well, it’s uncertain meaning. So I already know… nobody knows [what it means]. I guess, [I would want to know] if there’s anybody doing research on it, the possibility that there’d someday be an answer.” [Participant 48] Some participants mentioned wanting to learn how the variant could possibly affect their health: “I just want to know what it means, and they can’t tell me that… I think mostly what I want to learn about what it means is if it’s positive or negative… to my health… I would want to know if it’s helping me or hurting me.” [Participant 40].

For variants that increase risk of diseases that cannot be prevented or treated, participants were most interested in learning about their likelihood of getting the disease, often in quantitative terms. In addition to their personal risk of disease, participants were also interested in learning whether the disease was hereditary, in order to learn if their family members would also be at risk: “I would want to know… the chances of carrying that gene on to other family members… I guess for your children you’d wanna know what their risk factors are, but then also their children… because that could continue to trickle down through the generations.” [Participant 30].

When asked about variants for which they were carriers, participants wanted to learn how their relatives would be affected, including the chance that the variant would be passed on to other family members and future generations. Participants stated they wanted to know this information in order to communicate effectively with family members. This was often framed around helping them make health-related decisions, navigate the genetic testing process, or offer informational or emotional support: “I would want to learn as much as I could, just like anything else. And help them navigate through the whole process of figuring out what they have to do.” [Participant 37].

Fewer participants were interested in learning specific information about variants not related to health (e.g., ancestry, physical traits), as information about this type of variant was often viewed as interesting, but not necessary: “It would only just be to satisfy curiosity… it would be interesting to learn.” [Participant 13] Of greatest interest to respondents was the meaning of the variant, including how this variant would present: “I’d wanna understand… if that variation means that I have green eyes or I’m tall, or if there’s any meaning to it.” [Participant 21] or what this information could tell them about their ancestry: “If having a certain gene tells you something about your ancestry and there’s something known about particular outcomes for people with that ancestry then that could be helpful information.” [Participant 22].

Amount of Information Wanted

In addressing the amount of information that they wanted, some participants highlighted the importance of providing information in a way that could be easily understood. This included participants who wanted to know everything: “I’d wanna know everything that was in the scientific literature… but in layman’s terms because I can’t always digest everything.” [Participant 60], as well as those who wanted only certain types of information: “just enough to have an understanding… a good, strong, laymen understanding.” [Participant 14].

The amount of information participants wanted to receive also varied by type of result. Many wanted to know everything available about variants that increase risk of a disease that can be prevented or treated, considering the information useful: “It’s about usefulness. Any information they can give me that is useful in maintaining good health.” [Participant 40] Most participants also wanted to know everything about carrier status variants in order to share and discuss this information with relatives: “Everything they could tell me so that when I tell my relatives… of course they’re gonna have all kinds of questions. I’d like to be able to answer those questions for them and say this is what I understood the doctor to say.” [Participant 24] Additionally, some participants wanted to know everything about variants that affect response to medication or treatment: “I would want to know as much as I could… to me everything is so interconnected in your body… I want to know it all.” [Participant 46].

There was more variability in the amount of information that participants wanted to receive for other types of results. For VUS, some participants weren’t sure what they could learn due to the current state of knowledge, so the amount of information wanted varied from nothing: “[I want to learn] nothing… it’s uncertain, so why create anxiety within the self?” [Participant 35] to everything available: “As much as I could as quickly as possible. I want more certain info – I want it to be less uncertain.” [Participant 34] For a few participants, interest in information about this type of result depended on whether it was specifically related to cancer: “I guess if there was something that was related to cancer I would probably be somewhat interested in finding out about that, but otherwise no.” [Participant 45].

For variants that increase risk of a disease that cannot be prevented or treated, we similarly observed that the desired amount of information varied from nothing: “I think if there’s just absolutely no prevention or treatment period, I don’t think I wanna know. There’s enough bad stuff out there.” [Participant 32], to as much as possible: “Again, if I already know [I have the variant], I’d want to know everything I can about it.” [Participant 47] Participants also varied in the amount they wanted to learn about variants not related to health. Some felt there was nothing to learn, while others felt ambivalent: “I don’t know. It’s just novel. It’s interesting to see how the statistics play out.” [Participant 1].

Discussion

This study explored what women diagnosed with breast cancer at a young age would want to learn when genome sequencing results are returned in order to inform the development of results feedback strategies that meet patients’ needs and preferences. Across different types of possible results, participants expressed interest in learning about health implications, risk and prevalence statistics, causes of the variant, and causes of diseases, both for themselves and for family members. The finding of the importance of health implications is consistent with prior literature; learning health information was a primary motivation to pursue genetic testing and genome sequencing in previous studies (Christenhusz et al. 2014; Facio et al. 2011; Hitch et al. 2014; Leventhal et al. 2013; O’Neill et al. 2013; Wright et al. 2014). For instance, focus group participants from a cohort undergoing clinical sequencing expected their results to provide information about their current or future health (Wright et al. 2014). Interest in risk information is also consistent with other findings; Leventhal et al. found that among primary care patients, a motivating reason for receiving genomic test results was to learn about personal and family members’ risk of disease (Leventhal et al. 2013).

However, our study adds to this literature in identifying other important topics. A novel finding in our study was interest in learning the prevalence of a specific variant in quantitative terms, specifically, how common the variant is among both the general population and specific, relevant populations such as breast cancer patients. Other studies have shown patients’ interest in how a variant contributes to the development of disease (Facio et al. 2011; Tabor et al. 2012). Indeed, in a study of healthy adults reviewing information about genetic susceptibility testing, participants were more interested in information about diseases than about the gene variants (Kaphingst et al. 2010). In this study, participants wanted to learn not only whether a variant causes diseases, but also what factors (e.g., inheritance, behavior, environment) cause a variation. We also observed that many of the participants’ responses were explicitly related to their diagnosis with breast cancer and that this experience therefore framed what information they would want about sequencing results. One possible reason is because many young breast cancer patients have had prior genetic testing and may have experience with making decisions about genetic testing and the subsequent results. As such, these patients may be a more informed population compared to healthy patients with no exposure to genetic testing. This experience may influence patients’ interest in certain types of information about sequencing results and how they might use the information they learn, such as for prevention of other diseases. Future research should examine how this patient population uses sequencing results, including with whom they discuss their results and how it informs their decisions. Of note, participants did not prioritize learning genetics basics or how sequencing was done, even when prompted about these topics during the interview. Time spent on these topics during a results disclosure genetic counseling session may therefore not be meeting patients’ information needs.

In addition to these general information topics, we found that specific information topics of interest and the amount of information participants wanted to learn differed across the six types of results examined in this study. Little prior research has investigated differences in desired information across types of sequencing results. We found that participants were most likely to want extensive information for results for variants affecting risk of preventable or treatable disease, affecting medication or treatment response, and carrier status results. For these results, participants most wanted to learn about actionable topics, both for themselves and potentially for their families. This included information on how to lower risk or prevent disease onset, how to determine the best treatment for themselves, and how relatives would be affected. In contrast, we found greater variability in the amount of information that participants wanted about results for variants affecting risk of unpreventable or untreatable diseases, VUS, and variants unrelated to health. For these variants, participants were most interested in information topics related to current and future research on the meaning of variants, likelihood of developing diseases due to the variant, and information on ancestry, respectively. It is possible that the variability in participants’ level of interest for different types of variants may depend on their current stage of the cancer care continuum; for instance, patients who have recently been diagnosed may prioritize receiving information about variants that can be prevented or treated over VUS. Examining what information and the amount of information patients wish to learn at different stages of their cancer diagnosis, particularly for young breast cancer patients, is an area for further study. In addition, since our findings suggest patients may have different informational needs depending on the type of result, an important area for future research is to examine whether results feedback strategies may need to be tailored in content and amount of information by specific result types. Future research should also examine quantitatively whether the amount or content of information desired differs by patient characteristics, such as breast cancer diagnosis, family health history, or sociodemographic traits. Another direction for future research could be to assess the amount of information that patients want to receive using quantitative scales that measure level of interest and amount of preferred information for each type of result.

Prior studies have shown that participants generally hope to use results from sequencing to make lifestyle changes for prevention purposes, alter treatment strategies, inform future planning efforts, or alert family members of potential health risks (Hitch et al. 2014; Wright et al. 2014; Yu et al. 2014). These findings are consistent with our observation that participants are interested in actionable information when some types of sequencing results are returned. Similar to our participants’ interest in learning specific information about the future meaning of VUS, Wright et al. found that participants valued information even from variants that cannot be currently interpreted, understanding that there may be future utility (Wright et al. 2014). A novel finding in our study is interest in learning about the health implications of one’s ancestry. We hypothesize that this may be because of experiences this patient population has with cancers in their family and their interest in learning about how and why this occurs. While one recent study also found an interest in learning about ancestry from genome sequencing results, their findings were in the context of parents seeking information for their adoptive children (Crouch et al. 2015). Given the importance of family history in patients with cancer, we included this variable in our recruitment methods, stratifying by family history of breast cancer; however, differences in themes across these participant subgroups were not observed. It will be important to examine further interest in family history and ancestry information among those with a family history of cancer.

Our findings provide insight into what patients would want included in feedback about genome sequencing results for six variant types. It is imperative for clinicians to be able to comprehend genomic results, interpret them for individual patients, and effectively communicate this information. However, research shows many general practitioners lack sufficient knowledge and confidence about genetics and genomics (Gray et al. 2014; Selkirk et al. 2013). In response to these needs, Laughlin et al. developed an approach to facilitate return of individual results to physicians, using a concise genome report summarizing potential medical significance of incidental findings (McLaughlin et al. 2014). Similar efforts are needed to develop results feedback strategies for patients that meet their information needs and preferences, and importantly, strategies that are presented in a way that can be easily understood for patients. Specifically for VUS, results feedback should incorporate strategies to help patients cope with the uncertainty and minimize worry, beyond only providing information about the results.

Study Limitations

Study limitations should be considered. Participants in our study were predominately Caucasian and highly educated; while representative of the YWBCP cohort and early users of genome sequencing technologies, our sample is limited in racial and ethnic diversity and educational levels. There is also the potential for bias as participants who were more interested in genetic information may have been more likely to agree to an interview. Future research should examine information preferences in other, diverse populations. The information needs of the patients in our study may differ from those of healthy adults or populations examined in other studies (Schmidlen et al. 2014), as many young breast cancer patients have personal experiences with prior genetic testing. Patients with lower education and numeracy skills may also have different informational needs and preferences. We asked participants about their information preferences at varying times after their breast cancer diagnosis, including participants who may have been diagnosed many years ago prior to genetic testing or genome sequencing. These preferences could be different than those expressed at the time of diagnosis or those who have been recently diagnosed. Additionally, our findings report on preferences at a single point in time; however, preferences may change over time, including at different points across the cancer care continuum (Rutten et al. 2005; Taplin et al. 2012). We also were not able to examine patients’ reactions to actual results feedback, an important direction for future research. Furthermore, preferences and information needs regarding genome sequencing results may differ depending on whether patients have previously completed or are currently undergoing genome sequencing. At the time of this study, clinical sequencing was not yet being offered other than to diagnose rare conditions, making it unlikely that participants had undergone sequencing in the past. Therefore, another area for future research is to assess information needs from those undergoing sequencing. The Clinical Sequencing Exploratory Research (CSER) consortium has recruited both healthy patients as well as those with cancer and other medical conditions who have undergone sequencing (Green et al. 2016). As part of their work, the consortium is developing guidelines for consent and disclosure of findings; this work can provide further insight into the conversation of informational needs for different patient populations.

Conclusion

While previous studies have examined what types of sequencing results patients would want returned, our study focused on what information young breast cancer patients would want to learn if different types of sequencing results were returned to them. This latter type of information is critical in order to develop results feedback strategies for genome sequencing. While some information topics identified were consistent with existing literature examining what categories of results that patients would want returned, we identified a number of additional topics. Most notably, participants in our study expressed interest in learning about variant prevalence and ancestry information and emphasized that they wanted risk information in quantitative terms. In addition, participants did not prioritize learning genetic concepts or the basic mechanisms of inheritance, preferring instead to focus on the health implications of a result.

With the expanding clinical use of genome sequencing, our findings provide guidance to genetic counselors and clinicians in developing sequencing results feedback strategies that meet patients’ information needs and preferences. Our findings suggest that patients in this population will be most interested in learning about health implications, risk and prevalence statistics, causes of the variant, and causes of disease when sequencing results are returned to them. This study also identified information topics that could be discussed for different types of results. Women diagnosed with breast cancer at a young age recognize the potential value of genome sequencing results in identifying potential causes and effective treatments. Beyond its relevance to cancer, they also expressed interest in learning information about secondary findings that are unrelated to cancer and using the information to guide decisions to help relatives and to further understand their health risks. Participants also highlighted the importance of clearly conveying this information in lay language. These findings can therefore inform the development and testing of results feedback strategies. It will be important to investigate questions such as whether feedback strategies should be tailored by type of results and whether doing so leads to better counseling outcomes. As genome sequencing technologies continue to grow in importance in research and clinical settings, this communication research provides an essential patient perspective.