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”