Should all women undergo BRCA testing? This question has been an item for discussion once it was given the authoritative weight of Mary-Claire King, the widely respected genetics researcher who has made invaluable contributions to the discovery and elucidation of the BRCA genes. The appeal is clear. Under current protocols, many women at increased risk of carrying a pathogenic variant are not undergoing BRCA testing. It breaks my heart each time I meet with a 40 year old mother of young children who was just diagnosed with a preventible serous epithelial ovarian cancer or a triple negative breast cancer. Furthermore, a significant number of pathogenic variant carriers are missed by just about every set of testing guidelines. Not only that, guidelines are so complex, evolving, and variable that no one can keep track of them any more, except maybe the unsung heroes among the support staff at commercial laboratories who are tasked with verifying insurance coverage for genetic testing all day every day. I half-jokingly tell my oncology colleagues at tumor boards that my new criteria for genetic testing are are simple: 1) Does the patient have cancer? 2) Does the patient have genes?
I understand the appeal of population BRCA screening. Risk mitigation strategies and enhanced screening have the potential to reduce morbidity and mortality, or, more simply put, it could reduce suffering and saves lives. This benefit looms particularly large in the face of that sly and nasty devil, fallopian tube/ovarian cancer. But the benefits – and I don’t mean to diminish them – can lead us to subconsciously overstate upsides and downplay downsides. As Guido Calabresi and Philip Bobbitt pointed out more than 40 years ago, allocating medical care is full of tragic choices, i.e., no matter what course of action we choose, some people will suffer and some people will benefit. The hard part is deciding who should benefit and who should suffer. Let me be clear, though, that if BRCA population screening were to be implemented, I hope that my concerns prove to be unfounded or are addressed up front.
So what are my worries? First off, I am not convinced that population BRCA screening is high on the list of public health priorities in the US. It doesn’t make the CDC’s list of pressing public health initiatives. About 100 million Americans are affected with one or more neurological diseases. According to the USDA, in 2018 about 37 million Americans lived in food-insecure households, including 6 million children. Eight hundred thousand Americans will have a stroke this year. Half a million Americans struggle with homelessness. About 380,000 children are born prematurely. Forty thousand people die from a gun shot each year.
In comparison, my back of the napkin calculations suggest that of the approximately 42,000 breast cancer deaths and 14,000 ovarian cancer deaths in the US each year, roughly 5% of breast cancer patients and 15-20% of ovarian cancer patients carry a BRCA mutation (I am not including other high risk breast cancer related genes such as PALB2 and TP53, but their inclusion would not substantively change the calculations). This would amount to theoretically saving about 5000 lives annually. This rough estimate is based on the very unlikely assumptions of full population participation in both genetic testing and follow up cancer screening and risk reducing strategies, and that these strategies save lives. While the evidence is pretty good that risk-reducing saplingo-oophorectomy reduces ovarian cancer mortality in unaffected BRCA mutation carriers, the mortality/morbidity reduction benefit of combined mammography and breast MRI is less well established. Risk-reducing mastectomy significantly reduces breast cancer risk and disease and treatment morbidity but the mortality reduction is not as great as one would hope, especially as a woman gets older. And many healthy BRCA pathogenic variant carriers delay or decline mastectomy. At most, about half of unaffected BRCA pathogenic variant carriers undergo risk-reducing mastectomy.
Would the resources devoted to saving lives through population BRCA screening justify a reduction in allocation of resources to other far more common health problems or disparities within cancer care itself, such as racial and economic differences in access to care, morbidity, and mortality? Of course, numbers are not the only deciding factor for resource allocation, which is ultimately an ethical decision that society arrives at in a somewhat unpredictable and disorganized fashion. On the other hand, those numbers cannot be ignored. Population BRCA screening may prove to be cost-effective but that does not necessarily mean it would be the best use of limited health care dollars and resources. It is not exactly a zero sum game, but no matter how you slice and dice it, all health care problems cannot be covered with even the most generous allocation of resources. Eliminating the hundreds of billions of wasted health care dollars in the US might start to address resource limitations, but, realistically, drastic reductions in unnecessary spending are not likely to happen any time in the near future nor is it guaranteed that the saved dollars would be reapportioned to other areas of health care. Which lives “deserve” to be saved and which diseases “deserve” to be prevented? Tragic choices, indeed.
Then too there is the problem of health insurance, or, more precisely, the lack of it. BRCA testing on a population scale would presumably lower the cost of genetic analysis to affordable levels and labs would likely absorb the costs of those who can’t pay (or at least would figure it into their pricing). However, it is in the follow up of mutation carriers where the annual costs start to pile up. Annual mammography and breast MRI, mastectomy, reconstructive surgery, and salpingo-oophorectomy would not likely be available to the ~14% of the US population who lack health insurance, with even higher rates of non-insurance among young women, the very population who theoretically would benefit the most from BRCA testing. Yes, the cost of treating those women for cancer is much greater than the cost of screening and risk-reducing surgery, but if the women do not have the financial wherewithal to pay for surgery and screening then those interventions just aren’t going to happen. Before we even think too hard about implementing population BRCA screening, the national health insurance crisis must first be addressed. BRCA screening could unintentionally result in further health disparities for low income women.
Even among women identified at high risk of developing breast cancer and who have health insurance, uptake of MRI screening is low even in facilities where MRI screening is available, with some demographic variability in uptake. Thus, innovative efforts are needed to improve outreach, education, and motivation to participate in semi-annual screening that would likely last for decades. In addition, if population BRCA screening becomes a reality, more MRI machines will need to be purchased, more radiologists will need training if they don’t routinely read breast MRI images, and more surgeons will be needed to perform mastectomy and reconstruction. A commitment to BRCA screening requires a lot more resources than just increasing the availability of genetic testing.
I admit that I am a professional worrier, and maybe all of my concerns are just another expression of my character flaws. No doubt many of the Good Readers of The DNA Exchange will have strong differences of opinion with me. I want to save lives and avoid cancer treatments just as much as the next person, and maybe even more so than many others after having spent two plus decades watching women and their families go through the nasty physical and existentially threatening experience of chemotherapy, disfiguring surgery, radiation therapy, and dying all too young. On the other hand, there are many more people suffering from other serious and potentially preventible health problems. Are they less worthy? Tragic choices are so…..tragic.
” And tell me how does God choose,
Whose prayers does he refuse?”
– Tom Waits, “The Day After Tomorrow”
The DNA Exchange 
Whoah, you sure left us hanging between the public health priorities of paragraph three and the appearance of the eight-hundred pound gorilla of denial of any real health care insurance for many in the U.S. in paragraph six. (I nearly fired off an outraged comment of “but, but what about…” before even getting to six, but fortunately I’m not that kind of commenter.) How we can talk about “population” anything with still so many un- and underinsured in the US remains the central issue. To dangle the promise of universal screening of any public health sort with so many still without the means to do anything about it seems particularly cruel. But not any more so than simply ignoring those potentially at risk. (I just had to correct my Freudian typo of spelling that “portentially” at risk.) And probably much less cruel than many other realities of the current U.S. health “system” (and that within memory of most readers, not of advanced age). Like, say, the denial of any treatment or medical care at all to the legions of mentally ill homeless in any U.S. community. Or the need for GoFundMe crusades piled atop all the other devastation brought down by a cancer diagnosis and desperate need for treatment.
Anyway, as usual, thank you for the great piece, Bob, and always raising the issues that need to be raised.
By the way, your piece has been added to GeneLit.com, the hand-curated repository of all current medical literature (and much current relevant press) on Hereditary Breast and Ovarian Cancer, for medical and genetics providers, and any others with an interest or stake.
Hi Bob!
Thanks for this thought-provoking article. I’m glad you’ve opened the door to discussion while welcoming all opinions 🙂
While the CDC calls out a list of pressing health topics as you reference, they also indicate HBOC as a Tier 1 genomic application (https://www.cdc.gov/genomics/implementation/toolkit/tier1.htm), defined as “those having significant potential for positive impact on public health based on available evidence-based guidelines and recommendations.” While we have to balance broader public health initiatives, HBOC (via underlying germline changes in BRCA1/BRCA2) is, in fact, directly called out by the CDC and should warrant broader discussion on how to implement broadly by our community.
Additionally, a student at Northwestern surveyed genetic counselors on this very topic – GC attitudes, perceptions and perspectives on population-based screening for BRCA1/BRCA2 and Lynch syndrome. We’re readying the publication now for submission and it addresses a variety of GC opinions across the factors you mentioned! I’ll link it here if/when it is out in JGC. All that to say, I don’t think you’re the only “professional worrier” and that GCs feel this is a really complex issue. Ultimately, I think we, as genetic counselors, need to choose if we’d like to remain as worriers or move into proactively addressing our concerns in multidisciplinary ways to ready ourselves, care teams, and the health system for broadening test offering/adoption even if population screening is down the line because guidelines are ever expanding like ASBS’ call for ‘all breast’ to be offered testing). If we sit and simply point out what could go wrong without activity to rectify or research, it does not position us as leaders in this space or ensure our clinics are engaging in creating scalable service delivery models.
Thanks again for starting this discussion!
Leslie
Yes, CDC identifies HBOC as a Tier 1 genomic application, but neither CDC or the USPSTF are calling for population screening yet. (by the way, I agree with Colin Pritchard’s recent editorial suggesting we get retire the term HBOC because, well, it just doesn’t quite cover the current world of multigene panels – https://www.nature.com/articles/d41586-019-02015-7)
But yes, better implementation of testing AND appropriate resources for follow-up care are very important. The GC community should be at the core of research studies that address this question of how best to make sure that those who would benefit from genetic testing get access to it and that the testing really has the benefits that we claim. To some extent, I am not too worried about future GC involvement in this process. I take heart from the fact that historically genetic counselors have always, always been at the forefront of integrating genetic medicine into patient care, going back to the early days of prenatal testing in the 1970s (that was even before I was in practice!). Of course, there has always been some push and pull within the GC community as any new test is worked into practice. So I think it is okay to worry (or maybe that’s just some personal bias) as long as the worry isn’t crippling. Sometimes the worriers are right, and sometimes they are wrong. The data should help sort that out.
Great reply, by the way.
Bob
The fact is we already have universal BRCA screening, but only for those with education and resources. I bet a fair number of the readers of this article have gotten themselves tested one way or another without meeting traditional criteria. I certainly did. Opening up access (both education and actual testing/support) to more folks just means less inequity. The days of only folks meeting guidelines getting testing are long behind us.
And yes, there are many other competing needs for healthcare dollars, but maintaining inequitable access to genomic information based on ability to pay (and sufficient education to seek it out) won’t fix the mental health crisis in this country. It isn’t zero sum. it is much more complex than that.
disagree that “opening up access…just means less inequity”.
it is not nearly that simple.
genetic testing/risk assessment is the first step, yes.
but the real burden comes with completing the necessary follow up (surveillance, surgery, etc.).
until we have equitable access to and support for appropriate follow-up, knowledge of one’s BRCA1/2 status is necessary but not sufficient.
I agree, Emily, that inequity extends far beyond HBOC testing, but it is part. And with better access to all of it (counseling’s, education, testing, downstream care, etc) we can begin to confront that. I also don’t think guidelines on testing will improve downstream access. The whole system is fraught and inequitable access to HBOC testing propped up by guidelines doesn’t help. But this is one step toward fewer barriers. There is no panacea but we can’t give up. There is clearly much work for all of us to do in every corner of healthcare provision.
Carrie
Thanks for a thoughtful reply. So let me raise a few counterpoints. First off, if testing is still not available to a sizable chunk of the population who don’t have the resources or savvy (which I prefer to education), I don’t think you can call it universal yet (though of course it may be universal one day). It’s more privilege-based screening than universal. Second, while I whole-heartedly agree that criteria-based testing has it’s problems and may eventually fade into the sunset, it is not yet a thing of the past by any means. For now, health insurers still use guidelines to determine coverage. I am still dealing with insurance guidelines for my patients every day. Sure lots of patients can afford $250 to pay OOP, but lots can’t, either. Unless of course they are getting testing through an employer-sponsored program, which is another form of privilege-based screening (and one that also makes me worry but that’s a topic for another blogpost). Third, as Emily points out, the problem isn’t really access to testing (which certainly needs to be better); the problem is access to care for followup screening/surgery/whatever. It’s not really benefiting a patient if they can get a genetic test at low or no cost if they can’t act on the information. In my view, that’s not genomic equity. Access to genomic information can’t occur in isolation from access to other aspects of health care. So, to some extent, it is still a resource allocation issue. Where does society see the most benefit in allocating financial and other medical resources? Ultimately, society decides, but if GCs think that society does indeed benefit from universal BRCA screening, then we are going to have to make a better case for how we would address the details of downstream costs, uninsured patients, more clear cut morbidity and mortality reduction benefits when applied at a population level (which is very different than at a clinical level), keeping women on a high risk screening protocol for several decades, etc.
I am still working through and processing my own thoughts on this, so I am interested in your thoughts to further help me figure this out. It is a great topic for a nice, juicy, and fruitful discussion.
I totally agree, Bob. My point was exactly that the guidelines are already moot for those with privilege, both in terms of accessing the test as well as any necessary downstream care. So there is universal screening but only for a privileged and “savvy” (I like that term) subset so guidelines, in my opinion, further that privilege gap providing excuse to continue disparity in care. We have all spent way too much time fighting to get patients access to testing or services. The guidelines do not prevent people who shouldn’t have the test from getting it, but do prevent some of those who should get the test (as well as downstream care) from getting it. We just need to be clear about that and recognize the resulting inequality. And I recognize this is a teensy bit of the inequity built into our health system, but that doesn’t mean it (and our role in it) shouldn’t be examined and confronted.
Screening procedures in medicine have their own problems (see: mammography and still ongoing debate around it), but with BRCA we have more important, technical problem. Currently, all tests rely on SNPs, which are popular in particular population with particular ethnicity – mainly white, for instance. However, there are many places in BRCA genes, where mutations can disrupt their function, and we need to look even for those that will be encountered for the first time. That’s where we need sequencing of the whole gene and that’s the technical problem comes onto the stage: cost of sequencing. With current state-of-the-art machines, its still around $500-1000 for those few genes. I don’t think we’ll see any progress until the cost of real BRCA check (not just popular SNPs) will significantly decrease.
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