Dealing with the unexpected: consumer responses to direct-access BRCA mutation testing

Study population

We identified 204 BRCA1 (185delAG or 5382insC) or BRCA2 6174delT mutation carriers (130 males and 74 females) in the 23andMe database of 114,627 customers who were at least 18 years of age and had consented to participate in research. The male–female ratio reflects the gender distribution in the overall 23andMe customer base. Of the 204 mutation carriers, 136 (67%), 77 men (59%) and 59 women (80%), had viewed their BRCA report and were invited to participate in this study. In comparison, 65% of all customers in the database had viewed their BRCA report (63% of males and 67% of females). We selected a control group of customers who did not have one of the three BRCA mutations, matched to the mutation carriers by age, sex and ancestry. Five mutation-negative participants were unable to recall their BRCA results and therefore did not complete the full interview. Two rounds of recruitment were required to recruit a comparable number of mutation-negative individuals. The demographics of the final set of individuals who completed interviews (32 mutation-positive “cases” and 31 mutation-negative “controls”) are detailed in Table 1. While the control group included a few more females than males, the age range and mean age were very similar.

Awareness of BRCA test and ancestry-based risk

At the time of purchase, only 13/32 (41%) cases were aware that BRCA testing was included in the PGS^®, compared to 20/31 (65%) of controls (Table 1). In contrast, 20/32 (63%) cases were aware that having Ashkenazi Jewish ancestry influences the risk of having one of the three BRCA mutations, compared to 13/31 (42%) of controls.

Personal and family history of cancer

Answers to the questions regarding personal and family history of cancer are summarized in Table 2. As expected, more cases than controls had a personal or family history of breast and ovarian cancer; there was little difference between cases and controls in terms of personal or family history of prostate and other cancers.

Viewing of the BRCA report

To avoid precipitating the discovery of a BRCA mutation in people who did not already know about their mutation status, we only invited customers to participate if they had chosen to view their BRCA report. In the current structure of the 23andMe results-reporting website, BRCA reports are “locked”, which means they require an additional customer approval step to “open” (display) the result. This feature enables customers to view other health reports before separately choosing to view the BRCA report. During the interview, we asked about their recollection of opening the report. Responses show that one case and nine controls did not remember whether the BRCA report required an extra step to open, and one case and five controls did not remember when they opened it. The majority, 24 cases (75%) and 18 controls (58%), however, remembered that they viewed it immediately, as soon as it was available to them (Table 3). Seven cases and eight controls waited for days to months before viewing their BRCA results. Reasons given for this delay included uncertainty about wanting to know, being too busy with other tasks, and not noticing the report until some later time.

Recollection of the BRCA test results

The blinded interviewer asked participants whether they remembered their BRCA results and what they learned from them. Five individuals did not remember their results and were excluded from further participation in the study. All of these were mutation-negative. Eleven women and 14 men stated that they learned for the first time that they had a mutation in either BRCA1 (n = 10) or BRCA2 (n = 15). Seven participants (five females and two males) knew prior to obtaining their results that they carried one of the three BRCA mutations that are tested for as part of the PGS^®. Confirmation of their carrier status by the PGS^® increased their confidence in 23andMe test results and encouraged some to initiate testing of their relatives who they understood might also be carriers. Reasons for prior BRCA testing included a diagnosis of breast and/or ovarian cancer (three women), or having a first-degree relative with breast and/or ovarian cancer – with and without a known BRCA mutation (two men and two women) (Table 3).

All participants in the control group recalled their negative mutation status correctly. None of the mutation-negative individuals had been tested previously, they first learned this information through the PGS^® testing. Mutation status as recalled by each participant was independently confirmed through inspection of the database.

Emotional responses to BRCA test results

Participants were asked about their initial emotional responses to seeing their 23andMe BRCA results. They were asked if they felt surprised by their results, and why or why not (Table 4). Ten mutation-positive individuals (six women and four men) who expressed surprise referenced the lack of a family history of breast or ovarian cancer or presence of only sporadic late-onset breast cancer, “not the genetic type”. Others were surprised because they believed the frequency of these mutations to be low in the general population.

Ten of the mutation-positive women were not surprised, including the five who had been previously tested, one who had close relatives known to be mutation-positive, and four others with a strong family history. The 12 mutation-positive men who were not surprised cited the following as reasons: two already knew about their mutation, one had a mutation-positive aunt, some had a positive family history of breast and/or ovarian cancer and others had realized they were at risk by having Ashkenazi Jewish ancestry.

Participants were read six options (which overlapped the Impact of Events Scale) and asked to choose which emotional response best fit how they felt at the time of receiving their results (Table 4). For the mutation-positive group, remarkably, none of the 32 reported having been “extremely upset”. Three of the four who were “moderately upset” were also “surprised” or “shocked” by discovering that they carried a BRCA mutation. The nine participants who said they had been “somewhat upset” initially, with anxiety subsequently subsiding, include three who were also “surprised”. Remarkably, nine women and eight men who were mutation positive reported feeling “neutral”. Of these 17, four women and two men already knew that they were BRCA mutation carriers. One female carrier was “relieved” to get confirmation of her previously known result. One young woman who was not “surprised” and felt “neutral” said:

“I wasn’t surprised. It didn’t come as a surprise and, like I said, it wasn’t scary to me and it wasn’t bad news. It was just kind of more information to work with I guess. Yeah. I think I’m the only person in my family who’s had this testing so far. And I maybe would have different feelings about my results if, you know, I lost my mother to breast cancer, if it was a more emotionally charged thing, or if I knew somebody else who had it or something like that. I think it would maybe feel differently, but as far as I know I’m the only person whose been tested for it”.

One male who learned about his carrier status for the first time reported feeling “relieved” because his daughter who was tested simultaneously by 23andMe had not inherited his mutation.

In the mutation-negative group, only one woman reported feeling “pleasantly surprised”; she also felt “extremely relieved” because she had a family history of breast, prostate and pancreatic cancer. The remaining 30 did not report feeling surprised, despite the fact that 12 had a family history of breast cancer in a first or second degree relative and one had a family history of ovarian cancer (Table 2). The emotional responses they identified most with were “neutral” or “relieved” (48% in each category), with 66% of the “relieved” responders being female (Table 4).

Effect of BRCA test results on perception of cancer risk

We explored whether knowing one’s BRCA status affected the perception of one’s own breast and ovarian cancer risk (for women) or breast and prostate cancer risk (for men). Most female carriers reported understanding their personal risk as significantly elevated, and several correctly recited the risk figures that they had learned from their 23andMe report for both cancers. Some stated that their perception had not changed much because they had always believed they were at high risk due to breast/ovarian cancer in close family members and Ashkenazi Jewish ancestry, but that knowing they had inherited a BRCA mutation made them more aware of the reality and prompted them to take action. In general, male mutation carriers perceived their personal risk for breast cancer to be low and their risk for prostate cancer to be slightly higher than average.

The majority of BRCA mutation-negative participants stated that they perceived their cancer risk to be unchanged; only one woman thought her risk was reduced. The majority said they felt relieved not to be at high risk but realized that other genetic factors and environmental factors can still cause them to develop breast or ovarian cancer. Several women expressed the understanding that only the three common BRCA mutations were included in this test and that other mutations in these genes may still be present. Some mentioned that they had a slightly higher than average risk based on their separate 23andMe breast cancer report covering seven variants in other genes known to be associated with breast cancer, further conveying their understanding that there are many other risk factors to consider beyond BRCA mutations. Not a single mutation-negative participant interpreted the negative BRCA test result as indicating no or significantly lower than average risk for these cancers.

Sharing of BRCA test results

We asked participants with whom they shared their BRCA results. The majority of mutation-positive participants shared their results with spouses/partners and blood relatives (Table 5). In addition, 50% (8 females, 8 males) shared their test results with friends, ranging from “a few friends” to “everybody”, which included using blogs or social media. Of the 32 mutation-positive participants, only two men had not yet shared it with anyone but said they were planning to share it with present or future spouses and other family members “as appropriate”.

The majority of mutation-negative participants shared their BRCA results with spouses and family members, and some (7/31) shared with friends or medical care providers. The remaining 12/31 (39%) did not share their result with anyone, stating that they didn’t feel it to be relevant (Table 5).

Communications with health care providers

Seven mutation-negative participants said they informed their primary care physician. Thirteen of the 16 mutation-positive women (including two who had previously tested positive) sought medical advice (most did so immediately) from their primary care physician, gynecologist or oncologist. Five consulted with a genetic counselor, usually upon referral from the primary care physician, who then coordinated repeat BRCA testing in a clinical lab (in most but not all cases) and referred them to an oncologist.

Overall, our interviews revealed that sharing of BRCA test results with physicians was more common amongst mutation-positive individuals (19/32 or 60%) than mutation-negative ones (8/31 or 26%), and within the mutation-positive group, it was also more common amongst women (13/16 or 81%) than men (6/16 or 38%). The three women who didn’t contact a physician when they got their result already knew that they were BRCA mutation-positive and had been treated for breast and/or ovarian cancer.

The rate at which mutation-negative participants shared their results with physicians is comparable to those reported in larger surveys of DTC customers: 27% (Bloss, Schork & Topol, 2011) and 20% (Kaufman et al., 2012). The high level of sharing with physicians for the mutation-positive women most likely reflects the actionability of the test results.

Some female mutation-carriers expressed feeling pressured into surgical procedures by physicians, and some stated that the full range of choices presented to them by genetic counselors had caused anxiety.

“It was a real shake up for me for a little while. But not because of my reaction to the BRCA2 results from 23andMe, but to the total fear factor that was put in by all of the traditional medical people; based on my doctor telling me if I didn’t get my breasts and my whole female organs out within 6 weeks, and by the way that date has long since passed.”

“At the beginning I was not anxious. It was very rational, you know, it is what it is. Later I had slight anxiety, because there are so many choices. So if it had been like so okay, this is, you know, one way to do the surgery, that’s fine. But then I went to the genetic counselor, it’s like so many choices, and whenever you have choices you have anxiety, because it’s time to research and make right decisions and so on.”

Although only a few mutation-negative females shared their results with physicians, those that did so felt their physician showed little interest, did not know what to do with the information or doubted the validity.

“I gave a full printout of my results to my primary care physician, just for the heck of it. But it really didn’t come up in conversation. I didn’t really talk about it. I didn’t think I was at risk because it confirmed like, oh, I’m not at risk and that was that.”

“I enabled my surgeon and my internist both to have access to the information that I received from 23andMe. But I think essentially their feeling was that it wasn’t really helpful you know that it was purely a survey. It didn’t provide the type of genetic information that they would find extremely helpful.”

“I shared the results with my physician when I did have the mammogram. She kind of looked at me like physicians don’t know how to handle this information because that’s not part of their routine. So I don’t know if she took it in and goes – okay I don’t know what to do with this, I’m gonna go with what I know [that] is order a mammogram.”

“And I was telling my doctor about this. And I said I had this analysis and it showed different likelihood of this and that. I didn’t mention the breast one because it was never a concern. And he said how much did it cost, and I said I think it was $150 a year or something like that. And he said ‘Well, how can they have good results for only that much?’ And I said they do. They really do a very careful analysis and they’re constantly bringing new results. So he wants to see it sometime, so I’ll have to print it out because he’s open to it”.

Actions taken or planned in response to BRCA report

Mutation-positive participants were asked about the immediate next steps they took after learning their results and what they were planning to do in the future (Table 6). In terms of immediate action, sharing results with family and friends was the most common response. The majority of women also sought medical advice. Prior to being tested by 23andMe, three women had been diagnosed with breast cancer and had undergone mastectomies and one had also undergone a prophylactic oophorectomy. There were 11 mutation-positive women who received this information through 23andMe for the first time. Among these 11 women the following actions were taken or are planned: one prophylactic mastectomy, three planned mastectomies, three oophorectomies, and four planned oophorectomies (after childbearing). Five said they went to have breast exams and breast imaging after getting their results, and the seven who neither had nor were planning to have mastectomies reported that they would continue to have regular breast cancer monitoring (Table 6).

In general, male carriers did not initially consult a physician; several stated that they were familiar with the literature, had done online research and/or were working as professionals in the field and did not feel they needed medical advice. The majority, 13/16 (81%), said they would seek or would continue to have regular breast and prostate cancer screening.

“It’s a little bit interesting as a male approaching this, because I can’t quite put myself in the female perspective. But the combinations of prophylactic type procedures that are available for a female with these results are very, very different than what’s available to me. So, no, I don’t have anything directly planned other than just to be aware.”

“Breast cancer, yeah, fairly low. I know it’s possible, but it’s not particularly common. I mean, I don’t know if the studies have been linked strongly with prostate cancer, but it follows in my family directly. So that’s the one I’ve been thinking about.”

“I might start my prostate cancer screening earlier, maybe at 45 or 40 even. I might tell my physician I have this gene and that it might be a good idea to get tested younger than the recommended age.”

The present study reveals that for those who received a positive BRCA test result from 23andMe, there was a distinctly positive effect of identifying additional family members at risk.

We observed a significant expansion in identification of BRCA carriers through testing of relatives of both female and male mutation carriers.

Male carrier: “My mother saw a genetic counselor as a result of my testing and my little sister saw a genetic counselor as a result of my test.”

At the time of our interviews, 30 secondary (family member) BRCA tests had been carried out as a result of the initial testing, either through physician channels or through 23andMe, with 13 positive and 17 negative results. In one of these mutation-positive secondary cases, early breast cancer (DCIS) was discovered by MRI, a sensitive imaging procedure usually offered as a screening test only to mutation-positive women (Robson & Offit, 2007). Several secondary cases with mutation-positive BRCA tests also underwent prophylactic mastectomy and oophorectomy and others indicated that they were planning to have both risk-reducing procedures in the future.

In retrospect: Perceived benefits outweigh harms

At the end of the interview, we asked participants whether they thought purchasing the PGS^® was worth it, whether they would do it again, and why or why not. 30/32 cases and 30/31 controls said they would do it again. The participants found the PGS^® worthwhile for several reasons; the most significant being that some mutation carriers felt it may have saved their lives or the lives of relatives who tested BRCA positive as a result of the primary participant being tested. In addition, participants received health information unrelated to BRCA that they found useful for personal risk assessments or family planning, or thought the PGS was worthwhile because they discovered or confirmed their ancestry, or just had their curiosity satisfied.

Positive impacts

Female carrier: “While the results were shocking and a little stressful, ultimately I think this could potentially change my life, and it obviously made a difference for my aunt, who was able to catch pre-cancer early. So I think all in all, it’s a positive thing. We would have never known, because there are no [affected] first and second-degree relatives. So until somebody ended up with breast or ovarian cancer I don’t think we would have known. This way we’re taking care of things prophylacticly.”

Female carrier: “Well, I got information that I could do something about. That’s what I’m telling people. You know, if you get information that you can do something about, and I think particularly Ashkenazi Jewish women, it’s certainly worth doing. I mean if someone did say to me ‘I don’t know what I would do with the information if I had that information,’ but I’m a proactive person, so it’s hard to imagine someone not doing something.”

Male carrier: “Even after I talked with genetic counselors, they never would have recommended me to be tested based on my family history that I knew of at the time. I feel like a genetic secret was found in my family. I feel like I may have saved my sister’s life. I mean, nobody knows. That’s a hard thing in our family because nobody had cancer early, but it makes a difference. You accept it. It’s in your system and I’m lucky enough to know that it’s there as opposed to finding out something too late. It increases your odds you’re going to find something and find it earlier.”

Male carrier: “I immediately had my children tested, finding that my daughter was predisposed (sic) to BRCA1 and she’s now being treated because of this. In other words, 23andMe may very well have saved my daughter’s life. My doctor and we have spoken to many, many of our friends to tell them about what we think about 23andMe. It’s all positive. I bet we’ve told 150 people.”

Male carrier: “Well, first off, specifically for this issue of the BRCA thing, it provided me information. We had cancer in the family. We had reason to wonder and it solved it very clearly relating to my daughter. I don’t think that learning that I have a few percentile or lower risk of anything is going to change my life, but some things are interesting, some things are informative and I think it’s important.”

Male carrier: “I think it’s good to know these things, regardless of whether it’s something you can control or do something about. In the case of this particular mutation, there’s only a 50% chance that if we had a daughter she would inherit the same gene. And maybe I would want – knowing now that I am a carrier – I would want, if we have a daughter, I would want her to get genetic screening. I think it’s a good thing.”

Male carrier: “And as healthcare becomes more and more streamlined and more specific, or I don’t know exactly what the word I’m looking for there is, but as it becomes more treatment focused that you need to be aware as possible of what your health situation is and what your risks are, because you can’t expect the healthcare provider to have all that information. You need to have your information, as much information as possible to make good decisions.”

Negative impacts

Only one of the 63 participants reported a negative impact. This participant was a mutation-positive man with a family history of breast cancer. He reported “emotional cost” and said he would prefer not to know his mutation status.

“I would not do it again, because it is really not information I need to know. I don’t think the cost in dollars was important, I think the emotional cost is more. The impact of the results to a greater extent was negative. It’s just basically knowing that I have it, I might pass it on. And that’s the main thing. Sometimes ignorance is better.”

In addition, one other case and one control said they would not purchase the 23andMe PGS^® again. One woman already knew that she was positive for the BRCA mutation and had had a double mastectomy in the past; therefore, she felt that her PGS^® result did not provide her new information. The mutation-negative participant who would not purchase the PGS again had received the kit as a gift and reported prior emotional instability as a reason for her preferring not to know:

“I guess denial is a pretty powerful feeling, and sometimes not knowing something helps you just forage through life without having some details that might cloud the way you perceive things. And so I guess a little bit of rosy-colored glasses would help someone like myself. I guess I don’t want to think negatively. Even if it were the truth, I might choose not to know that.”

Impact on male carriers

Many male carriers expressed strong concern about the risk of passing on a BRCA mutation to their daughters. Despite the fact that female carriers have the same risk of passing on the mutation, they did not mention this as a major concern since they were primarily focused on their own risk for disease and on making decisions about risk-reducing procedures.

Interview quotes from male carriers:

“I was never concerned for myself, even though when I found out, the first thing that came to my mind was: will my daughter carry this. So I was extremely concerned but not for me, if I answer extremely concerned, it wasn’t for me at all, but if you’re asking what my emotion was it was extreme concern, but not over my own situation.”

“I do see that I have a little chance of getting breast cancer even though I’m a male, and it’s probably increased in males with BRCA1 compared to normal males, but that is a very low chance. So I’m not worried about myself. I might be a little worried if I get married and have children, because it has 50% chance of passing on, and if the child is a female then she has a high risk…. initially my thought was I shouldn’t have children.”

“For breast cancer, I guess being a male the statistics are not so dramatic about that, what I read on your site about it. So as far as my health is concerned, and I can also compare to my father and grandfather who must have had the mutation, I’m at some risk to die sometime from something but it’s not really an anxiety factor. I would have been alarmed had I learned that my daughter had it, but I guess luckily she doesn’t.”

Comprehension of report

We scrutinized the interview transcripts for any evidence of misunderstanding of the information provided in the online BRCA report. One female mutation carrier was under the impression that all 23andMe health reports deal solely with disease probabilities, and did not appreciate that BRCA mutation testing provides a definitive answer about carrier status.

“I really read it as what it basically is. It’s not that I necessarily am a carrier. I’m just you know statistically it’s likely that I could be.” This participant was also confused about the mode of inheritance: “I have 5 children and 3 of them are daughters. Well it doesn’t matter because it’s gonna be passed through the boy.”

She had described her initial response as “surprised”, because her mother who had breast cancer was not Jewish, and her emotional reaction as “neutral”. She subsequently consulted with her physician and received post-test genetic counseling which she described as extremely upsetting and which did not alleviate her misunderstanding.

Two mutation-positive participants interpreted the fact that the BRCA report was initially “locked”, requiring an extra click to opt-in to view the report, as indicating a positive result:

“When you put a locked result on and you say this is locked, you don’t have to open it, well, everybody knows what that means. As soon as you say this result is locked and you can click here if you want to open it, you know it’s going to say something not good.”

“As soon as I saw it was locked, I opened it right away ‘cause I knew what it was. I mean there was no reason it was gonna be locked unless it was a mutation.”

There was no evidence among the mutation-negative group that any of them interpreted their data to suggest a significant reduction in breast cancer risk. All but one reported their perception of their own risk for breast and ovarian cancer to be unchanged after learning about their BRCA mutation-negative status.