Tag Archives: population BRCA screening

All For BRCA, BRCA For All?

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 prematurelyForty 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”


Filed under Robert Resta

Great Expectorations – A NextGenetic Counseling Model?

One of the few things we can all agree on is that there are few things we can all agree on. – Quote attributed to Yours Truly.

Genetic counselors have an uncanny knack for being in the right historical time and place. We have combined this historical luck with an almost naive courage in taking professional risks and parlayed them into a phenomenal growth rate for the profession. As soon as any new genetic testing technology was barely in the womb – amniocentesis, CVS, maternal serum screening, hereditary cancer testing, cardiac genetics, whole exome/genome sequencing – genetic counselors were there to gestate it and deliver it into medical practice.  We have frequently re-invented ourselves to meet the needs created by new technologies – cardiac counselors, neurogenetic counselors, oncogenetic counselors, whole exome counselors, lab counselors. But one area where we may have stumbled a bit is direct to consumer (DTC) genetic testing. How do genetic counselors fit into a service that wants to bypass genetic counseling and that so far has been of dubious clinical value?

In our e-tail world where you can purchase just about anything online, some version of genetic testing/counseling that bypasses the traditional clinician-in-the-clinic model seems inevitable. Indeed, Color Genomics, a biotech start-up backed by players in the genetics and tech communities, is now offering what is essentially a hybrid of the traditional genetic counseling paradigm with DTC testing for hereditary breast cancer risk assessment. Tests are ordered and interpreted by a physician “either your own or one designated by Color.” Patients request a test kit directly from the lab, provide a saliva sample and then mail the kit back to the lab. The 19 gene panel includes BRCA1/2 along with the usual list of genetic suspects – PALB2, CHEK2, etc. The same tests that we offer to patients in our clinics for thousands of dollars along with the hassles of dealing with insurers and the complexities of scheduling and paying for a genetic counseling appointment can now be had with a spit sample provided from the convenience of your home. No muss, no fuss, never needs ironing – and at the shockingly low cost of $249.

For many patients, the hardest part of genetic testing is actually making it into our offices. It takes a big emotional investment to make an appointment that might involve psychologically sensitive and scary information, several rounds of phone tag with the scheduler, figuring out an appointment time that fits into in busy family/work schedules, determining insurance coverage, and then having to deal with multiple appointments at institutions that require additional visits for a blood draw and for results disclosure. Not uncommonly, my patients’ medical records often indicate that the referring provider had recommended genetic counseling many times over several years. Nobody comes to see us until they are absolutely ready to do make the commitment to do so. The Color Genomics model, by comparison, makes the traditional approach look positively byzantine.

Sure, we want assurances from Color Genomics on technical details of the test such as depth of coverage, ability to detect the widest possible range of mutations,  follow-up on variants, etc. And we might question the success potential  of a business model that offers a test at one tenth or less  than what most competitors are charging. But this is a medically and financially savvy group, and I am willing to bet that they thoroughly addressed these issues before they launched this product. We can probably expect to see similar genetic testing start-ups in other areas of genetic testing.

With an estimated turn-around time of 6-12 weeks, this test is not for cancer patients looking to make a surgical decision in a few weeks. And, interestingly, $249 is more than many of my patients typically pay for BRCA or multigene panels. Because most of my patients – especially those who are being treated for cancer – have already met their deductibles, their out-of-pocket costs for genetic testing are minimal, assuming they meet their insurers’ criteria for coverage for genetic testing. For now, at least, Color Genomics might appeal to patients who have large out-of-pocket expenses, or those who do not want to go through the “hassle” of face-to-face genetic counseling, or lack insurance coverage for genetic testing/counseling, or who do not meet their insurers’ criteria for coverage for genetic testing, or patients whose insurers don’t cover multigene panels. More to the business point, Color Genomics’ mission is Democratizing access to high-quality genetic information, consistent with the recommendations of Dr. Mary-Claire King, one of the company’s advisors, for all women to undergo genetic testing for hereditary cancer risk assessment (me, I am not a big fan of universal screening for anything, but that’s probably just one more area where I am in the decided minority, and I wince at the use of the word “democratizing”). Of course, if insurers get wind of this inexpensive pricing and require samples be sent to low cost labs, then there will be even less of an incentive for patients to go through the traditional genetic counseling/testing model (currently Color Genomics does not bill insurers).

I can hear the protests about the problems that will arise when genetic counselors are not involved face-to-face in pre-test genetic counseling. The wrong relative will be tested, inaccurate interpretations by patients and care providers, increased patient anxiety, inappropriate under- or over-utilization of high risk screening and surgery. But we largely have only ourselves to blame. With a few exceptions and some small case series, the genetic counseling community has done little research to prove that meeting with a genetic counselor prior to genetic testing makes for comparatively better health or psychosocial outcomes. And, at least for now, the early studies on DTC testing have so far concluded that most of our concerns about patient anxiety, inaccurate test interpretation, etc. are mostly unfounded (yes, I know we all have a story to tell that suggests otherwise but for now they are only stories).

But whether we like it or not, one form or another of this new genetic counseling/testing model is probably here to stay. In fact, I will venture the prediction that most genetic testing for cancer and other common conditions will eventually go around rather than through clinic-based genetic counselors. It is convenient for patients, saves money (until we can prove otherwise), and may be every bit as good as we are in educating patients. Private labs, unlike most clinics and hospitals, have the great good sense to invest the resources in developing highly readable websites that include explanations, information, and graphics to help patients better understand their results (personally, I think that lab-provided education can subtly bias the information to make disease risks seem higher and interventions more beneficial, but that is a topic for another day).

So maybe it is time for genetic counselors to again re-invent ourselves. Perhaps the classic model of pre-test counseling is mired in twentieth century ethical and technological paradigms. New employment opportunities and roles for genetic counselors in labs will develop and labs may eventually become the primary employers of genetic counselors. We will have to reconsider how genetic testing is arranged and managed in our clinics. And most critically, we will need to develop an ethical framework for delivering these services. Opportunities for conscious and unconscious conflicts of interest abound in all areas of genetic counseling, but perhaps most conspicuously in laboratory employment. Will we be swallowed by the business community and its emphasis on profits à la Milton Friedman, the influential economist? Will we become consciously or unconsciously less critical of the downsides and limits of genetic testing when profits and salaries depend on testing volumes? What are ethical and unethical behaviors for genetic counselors in these settings? Will psychosocial issues fall by the wayside? Frankly addressing these questions will make us uncomfortable, but no one ever said that genetic counseling would be an easy profession.


Filed under Robert Resta