Cancer Medicine Politics Popular culture Surgery

No, redefining cancer doesn’t mean death panels

Blogging is a rather immediate endeavor. Over the last nine years (nearly), I’ve lost track of how many times I saw something that I wanted to blog about but but by the time I got around to it was no longer topical. Usually what happens is that my Dug the Dog tendencies take over, as I’m distracted by yet another squirrel, although sometimes there are just too many targets topics and too little time. Fortunately, however, sometimes the issue is resurrected, sometimes in a really dumb way, such that I have an excuse to correct my previous oversight. This is just such a time, and the manner in which the topic has been resurrected is dumb. Thermonuclear stupid. Napalm-grade burning stupid. It’s a black hole of stupid that sucks any semblance of science, reason, or nuance out of any debate unfortunate enough to pass its event horizon. So let’s dig in. We’ll start with the idiocy and then use that as a “teachable moment” about cancer biology. Funny how I manage to do that sort of thing so often.

Abuse of cancer science for political purposes

As you might realize, I really hate seeing the willful misunderstanding of science misused for political ends. Specifically, I’m referring to the misuse of a legitimate scientific debate about cancer screening and diagnosis for purely political ends. First, however, for those not living in the US or my fellow citizens who might be blissfully unaware (in this case) of recent events, during the first half of October, our nation underwent what can only be described as a self-inflicted crisis that could have caused worldwide economic turmoil if it hadn’t been (sort of) resolved at the last minute. The reason for the crisis boiled down to the extreme resistance of some of our more radically conservative Representatives—to put it kindly—to the Patient Protection and Affordable Care Act, usually referred to as just the Affordable Care Act (ACA) or, colloquially, Obamacare. Normally, when I’ve written about Obamacare, it’s to complain about how advocates of unscientific medicine and outright quackery have tried to piggyback their advocacy on the ACA in order to have health insurance plans sold through government exchanges cover modalities like naturopathy, chiropractic, and other so-called “complementary and alternative medicine” (CAM) or “integrative medicine.” In related posts, I’ve examined the evidence with respect to the relationship between health insurance and mortality and whether attacks on Medicaid as not improving the health of patients insured by it have any validity. (Let’s just say they are oversimplifications and distortions.)

The claims I’m about to address come from a place every bit as brain dead any quack and seem to have originated from a article on Forbes by someone named Paul Hsieh, who claims to “cover health care and economics from a free-market perspective.” Imagine my relief, because he sure seems utterly unable to cover them from anything resembling a science-based prospective. Behold his op-ed, Why The Federal Government Wants To Redefine The Word ‘Cancer’. The insinuation (although Hsieh is quick to disingenuously deny that that’s what he’s really saying) is that the government wants to redefine cancer so that fewer patients will be diagnosed with cancer and qualify for treatment under Obamacare:

With respect to the definition of “cancer,” downgrading some conditions as no longer being “cancer” can and will used to justify reducing “unnecessary” screening tests (e.g., mammograms for women between ages 40-49). Mammograms can now detect the condition known as “ductal carcinoma in situ” (DCIS), which would no longer be called a cancer under the new proposal.

And, later, he writes:

I don’t believe the individual scientists arguing for a redefinition of cancer are driven by inappropriate political motives. But government will soon account for 66% of health spending and is aggressively seeking to limit health expenditures. Hence, the government may have a vested interest in definitions that err towards undertreatment, rather than overtreatment. We must remain vigilant against any attempts by the government to use language as a tool of covert rationing.

Imagine my relief that Hsieh doesn’t think those of us who are interested in reducing overtreatment are twirling our moustaches and rubbing our hands with glee as we plot on “death panels” how to deny mom and grandma her mammograms to save money, all in the service of Obamacare. I must admit, I tried to form a death panel, but I didn’t quite know how. Insurance companies are so much better at it, anyway. Either way, no, President Obama isn’t fixin’ death panels for your mama.

What Hsieh is referring to is an article published online in JAMA in July and in the dead tree edition by Laura J. Esserman, Ian M. Thompson, Jr., and Brian Reed entitled Overdiagnosis and Overtreatment in Cancer: An Opportunity for Improvement, a viewpoint report that was reported fairly widely in the media in Medscape, the New York Times, and NPR. The article, as I will discuss shortly, should not have been a surprise to anyone who regularly reads this blog or my writings at my not-so-super-secret other blog about overdiagnosis and overtreatment of cancer and the complexities of screening asymptomatic populations for cancers. As I’ve said time and time again, the relationship between early diagnosis and improvements in survival is complex and not nearly as clear-cut as most people, even most physicians, think. What Esserman et al discussed as part of their summary of recommendations of a working group at the National Cancer Institute was simply the next logical step, recommending possible strategies to reign in overdiagnosis without compromising treatment of potentially life-threatening cancers. Their recommendations are reasonable and science-based, although likely to be at least somewhat controversial. Near the end of his piece, Hsieh quotes Dr. Milton Wolf, who says something so that is so wrong on so many levels that one wishes it were possible to strip doctors of their medical licenses for spreading medical misinformation. Unfortunately, he’s just another right-wing hack doctor who really should know better but lets his dislike of Obamacare make him forget his medical knowledge:

Health care rationing takes many insidious forms but perhaps the most immoral is for the government to wage a public relations campaign designed specifically to dissuade patients and doctors from seeking available cures for cancer. They scheme to rename cancer, not to cure it, but to deny it exists. These government rationers have calculated that rather than actually treat patients with cancer, it’s cheaper to simply keep them as calm as Hindu cows right up to the very end.

I’ve noticed that radiologists (for example, Dr. Daniel Kopans) seem to be the ones most opposed to any recommendation that involves decreasing screening intensity or frequency. One notes that he is also a conservative Republican running for the Senate in Kansas who is in favor of defunding or repealing Obamacare. Ironically, he is also Barack Obama’s second cousin, who proudly proclaims, “I may not be the first doctor to oppose ObamaCare, but I am the first doctor from Barack Obama’s own family to oppose ObamaCare” and has even written an e-book entitled First, Do No Harm: The President’s Cousin Explains Why His Hippocratic Oath Requires Him to Oppose ObamaCare (Voices of the Tea Party). He’s also written articles with titles like The FDA’s one-man death panel and Tyranny in our time, criticizing his cousin and Obamacare. You get the idea.

Well, maybe you don’t. Hsieh and Dr. Wolf are downright reasonable in comparison to how the right wing blogosphere ran with this story. Here’s a sampling:

  • “It is plain and simply rationing of health care. And, at some point, rationing becomes a death sentence. So, in the opinion of your humble observer of the asylum we all have to live in, the House Republicans should go back to their original proposal to defund ObamaCare and each time the Senate sends the bill back to the House, they should just change the date and return it to the Senate. Keeping the government in partial shut-down may be a godsend.” – Asylum Watch.
  • “And why would the Obama administration want to re-define cancer? Because starting tomorrow, Obamacare will begin subsidizing millions of Americans’ health insurance, and cancer tests and treatments are expensive. This is nothing more than a back-door, roundabout form of rationing. It has nothing to do with improving health care or saving lives and everything to do with bureaucrats picking and choosing who gets what tests and treatments.” – Poor Richard’s News.
  • “Aren’t we glad that crazy Sarah Palin lady with her death panel rants didn’t get elected. And instead we live with a wise and sane government that fights new wars while renaming them as interventions and cures cancer by renaming it and denying coverage? Hope. Change. Death.” – Daniel Greenfield, Frontpage Mag.
  • “Cancer tests and treatment are expensive, and the government doesn’t want to foot the chemotherapy bill for lesions that don’t have a ‘reasonable likelihood of killing the patient.’ This redefining of the word cancer has absolutely nothing to do with improving healthcare, with saving lives, or with saving patients unnecessary anxiety; it is no more than an underhanded and surreptitious attempt at rationing. It is a cloak-and-dagger attempt to restrict who can benefit from healthcare system overpromised to us by Obama himself.’ – Crissy Brown, Thoughts on Liberty.
  • “One of the great problems in allowing the government– especially one proven to be untrustworthy by a number of recent high-profile scandals– to run health care and judiciously dole treatments with an idea toward cost-saving, is that the truth becomes completely lost. Any sort of trust that is supposed to exist between patient and doctor is lost as doctors are required to redefine, to the point of untruth, diagnoses, treatment options, and future prognosis due to the federal legal requirements. It’s Orwellian and wrong. And it’s guaranteed by ObamaCare.” – Yukio Ngaby at the very much misnamed Critical Narrative.
  • “The government wants to redefine the word “cancer” in order to have fewer conditions that can be classified as actual cancer. I’m going to go out on a limb here and ask… they really believe changing a couple of definitions is really going to help lessen the lives taken by cancer? I mean, if you paint a coconut pink it is still a coconut isn’t it?” – The Black Sheep Conservative.

I’m going to go out on a limb here (actually, no I’m not) and say bluntly that all of these criticisms represent such a level of burning stupid about cancer that one wishes it could be used to “cut, poison, and burn,” as the quacks refer to conventional cancer treatment. The argon beam coagulator burns less than these nonsensical ravings burn my neurons. At their black heart, they all boil down to a conspiracy-minded belief that the government (via the NCI) wants to redefine cancer in order not to have to treat people with cancer, allowing the, to thereby save money, no matter how many lives this costs. Of course, it never occurred to them that, given that by definition overdiagnosis and overtreatment mean diagnosing cancer that will never threaten the life of the patient and treating such cancers unnecessarily, reducing overdiagnosis and overtreatment is a desirable goal, both from the standpoint of improving patient care (overtreatment is all risk and no benefit, after all) and decreasing costs. This is the problem with science-based guidelines rooted in new understandings of cancer biology. Reasonable recommendations about how to decrease the rate of overdiagnosis and overtreatment are immediately seized upon by activists. Unfortunately, as can be seen from Dr. Wolf’s likening of such recommendations to slaughtering cattle, a lot of physicians share in this ignorance. (One also notes that Dr. Wolf really needs to read up on the Hindu religion.) With that in mind, let’s look at what Esserman et al actually wrote and recommended.

Redefining cancer: What it really means

I’ve discussed ductal carcinoma in situ (DCIS) before on multiple occasions. To recap, DCIS is a condition in which malignant-appearing ductal cells are observed in the milk ducts of the breast but have not yet invaded through the membrane surrounding the duct to get into the tissue outside of the duct. To put it simply, that’s basically what “in situ” means, that the cancerous cells have not yet invaded the basement membrane. There are quite a few epithelial cancers that have an carcinoma in situ stage: breast, colon, bladder, prostate, and others. In breast, DCIS is generally considered “stage 0” cancer, and treatment has a very high success rate. The reason for this success is likely because a lot of DCIS, possibly even most DCIS, never progresses to invasive cancer or progresses so slowly that the women who have it die of something else (such as old age) before it ever causes a problem. Indeed, it is estimated that low grade DCIS, if it progresses, does so within a time frame of 5 to 40 years and possibly in only 20% of DCIS cases, while high grade DCIS is more likely to progress. The same sort of behavior occurs with a lot of early stage prostate cancer in men. Since I’m a breast cancer surgeon, most of my examples will come from breast cancer. In other words, premalignant lesions are not one disease, and many of them will never cause harm within the remaining lifetime of the person harboring them.

The fact is that before the advent of widespread mammographic screening, DCIS was a relatively uncommon diagnosis. Now, thirty years or so after mass mammographic screening programs became widespread, DCIS is common. Indeed, approximately 40% of breast cancer diagnoses are in fact DCIS. Indeed, a recent study found that DCIS incidence rose from 1.87 per 100,000 in the mid-1970s to 32.5 in 2004. That’s a more than 16-fold increase over 30 years, and it’s pretty much all due to the introduction of mammographic screening of asymptomatic women. One potential reason is that by the time DCIS progresses to the point of being detectable by means other than mammography (such as feeling a breast mass), it has usually progressed to invasive ductal cancer. Another potential reason is that much of the DCIS we detect by mammography doesn’t progress to become symptomatic and threaten the life of the woman. Probably both mechanisms are in play. Either way, we don’t know for sure what percentage of DCIS lesions progress to cancer, and, in fact, we don’t know for sure whether the progression from normal ductal cells to cancer necessarily goes through DCIS. (Yes, I am a co-author on this paper and helped with much of the clinical discussion.) Indeed, there are currently three main models, all of which might contribute in different specific cases of DCIS, for how infiltrating ductal cancer (IDC) arises:


Supporting the hypothesis that something more than just a straight linear model of breast cancer progression is most in line with how breast cancer develops is the observation that, although the diagnosis of breast cancer has very much slanted much more towards DCIS and early stage (stage I and II) cancers over the last 30 years, detecting and treating these cancers aggressively has not resulted in a proportionate decrease in metastatic and locally advanced cancers. This was reported in the New England Journal of Medicine last December and is in line with other studies that I’ve mentioned finding that one in three breast cancers diagnosed by mammographic screening could be overdiagnosed and that one in five might spontaneously regress without treatment. Indeed, it’s becoming increasingly apparent that even a subset of frankly invasive cancers either don’t progress, progress so slowly that they won’t cause harm, or even regress. Treating these lesions provides no benefit to women, but does produce risk. In other words, these lesions (in this case, DCIS) that we refer to as “cancer” might better be considered something else, as many of them might not behave like cancer at all, at least not as defined as inevitably progressing, if left untreated, into a cancer that will threaten a woman’s life within her natural lifespan. Some are likely to be very indolent; some might even regress.

Who wouldn’t want to reduce the number of patients who are overtreated, and who wouldn’t want to name these premalignant, possibly malignant, conditions more accurately? Although part of this debate does have something to do with decreasing costs, contrary to what the fractally wrong quotes above more than insinuate, the primary reason is to decrease the number of patients subjected to potentially toxic therapies like radiation, surgery, and even chemotherapy for lesions that would cause no harm in their lifetime. The problem, as I’ve pointed out time and time again, is that we don’t yet know how to distinguish the in situ and early invasive cancers that are harmless from the ones that will progress. Until we can do that, we as physicians feel obligated to treat all of them aggressively.

With this background in mind, the recommendations by Esserman et al seem downright reasonable, mainly because they are downright reasonable, beginning with the introduction:

Over the past 30 years, awareness and screening have led to an emphasis on early diagnosis of cancer. Although the goals of these efforts were to reduce the rate of late-stage disease and decrease cancer mortality, secular trends and clinical trials suggest that these goals have not been met; national data demonstrate significant increases in early-stage disease, without a proportional decline in later-stage disease. What has emerged has been an appreciation of the complexity of the pathologic condition called cancer.The word “cancer” often invokes the specter of an inexorably lethal process; however, cancers are heterogeneous and can follow multiple paths, not all of which progress to metastases and death, and include indolent disease that causes no harm during the patient’s lifetime. Better biology alone can explain better outcomes. Although this complexity complicates the goal of early diagnosis, its recognition provides an opportunity to adapt cancer screening with a focus on identifying and treating those conditions most likely associated with morbidity and mortality.

Changes in cancer incidence and mortality reveal three patterns that emerged after inception of screening (Table). Screening for breast cancer and prostate cancer appears to detect more cancers that are potentially clinically insignificant. Lung cancer may follow this pattern if high-risk screening is adopted. Barrett esophagus and ductal carcinoma of the breast are examples for which the detection and removal of lesions considered precancerous have not led to lower incidence of invasive cancer. In contrast, colon and cervical cancer are examples of effective screening programs in which early detection and removal of precancerous lesions have reduced incidence as well as late-stage disease. Thyroid cancers and melanoma are examples for which screening has expanded and, along with it, the detection of indolent disease.

All of which is basically what I’ve been saying, with the addition of the examples of cervical and colorectal cancer, which do appear to behave in a manner consistent with a more linear progression model, which means that removing early stage disease does effectively prevent the appearance of late stage disease. Based on these observations, here is what the NCI recommends, with my comment afterward

  • Physicians, patients,andthe general public must recognize that overdiagnosis is common and occurs more frequently with cancer screening. [Note: This is nothing that I haven’t been saying for at least four years now, ever since I started to appreciate the complexities of screening for cancer.]
  • Change cancer terminology based on companion diagnostics. Use of the term “cancer” should be reserved for describing lesions with a reasonable likelihood of lethal progression if left untreated. There are two opportunities for change. First, premalignant conditions (eg, ductal carcinoma in situ or high-grade prostatic intraepithelial neoplasia) should not be labeled as cancers or neoplasia, nor should the word “cancer” be in the name. Second, molecular diagnostic tools that identify indolent or low-risk lesions need to be adopted and validated. Another step is to reclassify such cancers as IDLE (indolent lesions of epithelial origin) conditions. [Note: Again, if you understand the more recent data with respect to screening certain cancers, none of this is an attempt by the evil government to withhold vital care from cancer patients. It is actually an attempt to improve the care of cancer patients by decreasing overdiagnosis and more carefully “personalizing”—if you’ll excuse the use of this overused term—care to the patient’s tumor.]
  • Create observational registries for low malignant potential lesions. Providing patients and clinicians with pathologic diagnosis and information related to disease prognosis is crucial to informed decision making, including comfort with alternate treatment strategies such as active surveillance. [Note: Again, if we are truly going to “personalize” the treatment of lesions of low malignant potential, we need better information about what percentage of them progress into life-threatening malignancy and over what time frame they do so in order to facilitate shared decision-making between physician and patient. Again, this is not withholding treatment; this is empowering patients based on scientific findings to make decisions regarding their care with which they are comfortable.]
  • Mitigate overdiagnosis. Strategies to reduce detection of indolent disease include reducing low-yield diagnostic evaluations appropriately, reducing frequency of screening examinations, focusing screening on high-risk populations, raising thresholds for recall and biopsy, and testing the safety and efficacy of risk-based screening approaches to improve selection of patients for cancer screening. [Note: Again, this is nothing that I haven’t discussed in depth many times, beginning with the USPSTF recommendations for mammography. Unfortunately, any attempt to decrease screening inevitably runs into criticism that we’ll be “killing patients,” because the idea that premalignant diseases inevitably progress to life-threatening cancer is deeply embedded not only in the popular concept of cancer, but in the medical profession itself. Indeed, physicians even go so far as to erroneously blame the New York Times for killing patients by publicizing the problems with screening tests for cancer, like PSA testing.]
  • Expand the concept of how to approach cancer progression. Future research should include controlling the environment in which precancerous and cancerous conditions arise, as an alternative to surgical excision. [Note: I must admit that this one left me scratching my head a bit. What, specifically, does this mean in practice? I must admit that I don’t know.]

Esserman et al conclude by pointing out that much of this is an issue of communication as much as it is of science. After all, for the last 30-40 years, the medical profession and public health officials have been drumming it into our heads that we have to catch cancer early and that screening tests are the best way to do it, without also pointing out that every medical tests have risks and benefits. Yes, catching cancer early tends to be better in many ways. Treatment is more likely to be successful (or at least appear so) and, in the case of many cancers, can be achieved without much less aggressive and disfiguring surgeries. In my field, the example of doing a lumpectomy compared to being forced to do a mastectomy comes to mind. However, much more difficult is explaining how much of that improved survival is due to lead time bias and how much is due to treatment and early detection (as I’ve discussed many times before). It’s also hard to include in such discussions the concept of length bias, in which most cancer screening tests are biased towards detecting slower-growing, more indolent disease. As I’ve discussed before as well, to avert one death from breast cancer with mammographic screening for women between the ages of 50-70, 838 women need to be screened over 6 years for a total of 5,866 screening visits, to detect 18 invasive cancers and 6 instances of DCIS. The additional price of this was estimated to be 90 biopsies and 535 recalls for additional imaging, as well as many cancers treated as if they were life threatening when they are not. To prevent one death from prostate cancer, 1,410 men need to be screened over 9 years, for a total of 2,397 screening visits and 48 cancers detected. In other words, screening takes a lot of effort for, on an absolute basis, not as many lives saved as most people, even doctors, believe.

When taken in this context, all Esserman et al are saying is that we need to screen smarter, not more, and that we need to adjust our terminology and treatments to be more in line with our more recent understanding of biology. As Dr. Otis Brawley, chief medical officer of the American Cancer Society, put it so aptly, “We need a 21st-century definition of cancer instead of a 19th-century definition of cancer, which is what we’ve been using.” He’s right. Most of our definitions of carcinoma, carcinoma in situ, and premalignant conditions date back over 100 years and were based largely on what could be observed about tumors under the microscope. In 2013, we now have the tools to probe the molecular pathways that define and drive the progression of cancer.


There is actually one point that the cranks attacking the recommendations of the NCI panel make that has some validity, just not in the way that they think it does. That point is that words have power, and the word “cancer” has particular power. Of course, the cranks think that the reason the NCI is suggesting ceasing to use the word “cancer” to describe conditions that appear cancerous using old criteria but are not likely to harm patients who have them is to deceive patients and doctors into accepting less care in order to save money. In reality, it is a plea to bring language more into line with new science, based on concern among doctors that “hundreds of thousands of men and women are undergoing needless and sometimes disfiguring and harmful treatments for premalignant and cancerous lesions that are so slow growing they are unlikely to ever cause harm.” At the same time, we do not want to go too far in the opposite direction and err on the side of overtreatment.

Frequently referenced in discussions of the NCI recommendations is another study that I had meant to blog about when it first came out but got distracted by my Dug the Dog tendencies. (It came out about the same time as the NCI recommendations saw print.) This study by Omer et al examined the effect of how DCIS is described on the treatment choices of women. In the study, 394 women without a history of breast cancer were presented with three scenarios that described ductal carcinoma in situ (DCIS) as noninvasive breast cancer, breast lesion, or abnormal cells. They were then asked to choose among three treatment options: surgery, medication, or active surveillance. When DCIS was described as noninvasive cancer, 53% favored nonsurgical options. However, 63% chose nonsurgical options when the term used was breast lesion, a number that rose to 69% when the term used was abnormal cells. The authors concluded:

We conclude that the terminology used to describe DCIS has a significant and important impact on patients’ perceptions of treatment alternatives. Health care providers who use ‘cancer’ to describe DCIS must be particularly assiduous in ensuring that patients understand the important distinctions between DCIS and invasive cancer.

Or, as Ian Thompson put it:

“That is the real world of this when you include the word ‘cancer,’” Dr. Thompson said. “Because the word ‘cancer’ has a connotation that is profoundly bad.” The word “precancerous” has that same connotation. “That means the shoe is going to drop sometime down the road and that you are irresponsible if you don’t do anything about it,” he continued.

The consequences of the use of the word “cancer” to describe conditions that are only somewhat likely to progress can be seen all around us. For instance, the NPR article on the NCI recommendations tells the story of a 42-year-old woman who was diagnosed with DCIS and decided that she wanted a double mastectomy. In fact, I was shocked to learn that 6% of women with DCIS opt to undergo double mastectomy, which is massive overkill for such lesions that will not decrease the risk of dying of breast cancer. The consequences are found in women with DCIS being pressured by well-meaning doctors to have surgery right away, as if DCIS will turn into cancer overnight if they don’t act. It won’t.

In the end, dealing with premalignant lesions comes down to three things. First, we desperately need more accurate methods of risk assessment that allow us to accurately predict the likelihood that a given lesion will progress into cancer. Second, we have to get rid of the mindset that all precancerous lesions will inevitably “turn into” cancer. They won’t, and which ones are dangerous depends on the cancer type, observable characteristics such as nuclear grade, and molecular characteristics that we haven’t dissected yet. Finally, it’s a matter of communication. Telling people that finding cancer early is always better, that precancerous lesions found by screening will inevitably kill them if they don’t act, is based on an understanding of cancer progression that is decades old and no longer appropriate based on knowledge accumulated over the last two decades. It might be a cliche, but we need to screen smarter, not more, and we need to be able to explain that not all premalignant lesions require aggressive treatment.

It’s not going to be easy to change this culture and mindset, though, not the least of which because of cynical pundits like Paul Hsieh and Mark Wolf trying to convince people for their own political purposes that any effort to decrease screening or more accurately describe premalignant lesions that are unlikely to cause harm as somehow wanting to let cancer patients die in order to save money. The next time you see one of them doing that, please send a bit of Insolence their way.

By Orac

Orac is the nom de blog of a humble surgeon/scientist who has an ego just big enough to delude himself that someone, somewhere might actually give a rodent's posterior about his copious verbal meanderings, but just barely small enough to admit to himself that few probably will. That surgeon is otherwise known as David Gorski.

That this particular surgeon has chosen his nom de blog based on a rather cranky and arrogant computer shaped like a clear box of blinking lights that he originally encountered when he became a fan of a 35 year old British SF television show whose special effects were renowned for their BBC/Doctor Who-style low budget look, but whose stories nonetheless resulted in some of the best, most innovative science fiction ever televised, should tell you nearly all that you need to know about Orac. (That, and the length of the preceding sentence.)

DISCLAIMER:: The various written meanderings here are the opinions of Orac and Orac alone, written on his own time. They should never be construed as representing the opinions of any other person or entity, especially Orac's cancer center, department of surgery, medical school, or university. Also note that Orac is nonpartisan; he is more than willing to criticize the statements of anyone, regardless of of political leanings, if that anyone advocates pseudoscience or quackery. Finally, medical commentary is not to be construed in any way as medical advice.

To contact Orac: [email protected]

50 replies on “No, redefining cancer doesn’t mean death panels”

I should point out here that money is a huge part of the problem. Notice that urologists are the ones most opposed to limiting screening prostate cancer, which, if widely adopted, would drive many urology practices into bankruptcy because, at least in my area, they have moved most of the treatment, diagnostic, and staging modalities into their offices, a major capital expense. It should be no mystery why many radiologists oppose limiting breast cancer screening.

I have no solution, unfortunately.

Of course, as has been pointed out, until the researchers come up with a way for us to identify those lesions that are unlikely to progress during the expected lifetime of the patient, there will not be major changes.

I still don’t understand why Obamacare means death panels and paying for your own health-costs not. Well, no death panels perhaps, but if one can’t pay the costs for an expensive treatment, the result will be the same.
But well, I’m perhaps stupid, because I live in a country with a public healthcare system, where everyone is supposed to have an insurance for health costs, and I like it that way.


I think there are fundamentally two differences:

1. In the case of no government provided health care, there is no panel as such.

2. Assuming a government-run monopoly on health care (which some people assume is the intent of the ACA), a government organization could say that you cannot have treatment regardless of whether you have the means to pay for it.

Paul Hsieh, who claims to “cover health care and economics from a free-market perspective.”

Any time I see an article by someone claiming to have a “free-market perspective”, I expect hilarity to ensue. The so-called free market is a toy economics model which falls apart under any significant real-world scrutiny. In the case of health care, one of the free market assumptions which is obviously invalid is that consumers will shop around for the best price–if you get seriously sick or injured, you need to see the doctor ASAP, and you don’t have time to shop around.

@Renate: You aren’t being stupid here. “Death panels” was a cynical political claim of ACA opponents like Sarah Palin (a politician who is so clueless that she makes Paris Hilton look like an intellectual giant), and not something based on anything actually in the law.

Reading this I was reminded of something I saw on UK TV recently about whole body CT scans which is offered as screening to those that can afford it. They pointed out that a substantial percentage of us have some abnormality that will show up on CT – they gave the example of lung lesions caused by chicken pox – that will very probably not cause us any problems, but which doctors are obliged to follow up once they are aware of them. In this case the patient would very probably have been better off if they hadn’t had the CT in the first place.

Screening is a double-edged sword. A negative result may bring peace of mind, but a positive result may generate unnecessary worry as well as unnecessary investigations and treatment I have mentioned here before examples of my colleagues in clinical biochemistry who have had cause to regret doing tests on themselves, “just out of interest”.
One had an elevated serum bilirubin that turned out, after extensive investigations, to be Gilbert’s, a benign inborn error of metabolism. Another had an elevated CK, and underwent various investigations including muscle biopsies before it was realized that his “elevated” CK was perfectly normally in a sub-Saharan African.


Assuming a government-run monopoly on health care (which some people assume is the intent of the ACA), a government organization could say that you cannot have treatment regardless of whether you have the means to pay for it.

Why would anyone think that? Private health care is alive and well in the UK after 60+ years of something resembling socialized medicine. I very much doubt private medicine will ever disappear from the US. Why would it?

Krebiozen @5 — One thing to keep in mind with CT scans is that the radiation exposure involved is on the high side (if I recall correctly). CT scans are X-rays, which are ionizing radiation, not to be confused with MRI scans which should be pretty harmless. When a CT scan is medically indicated, you should not hesitate, but using them willy-nilly is perhaps not such a good idea.

Krebiozen — because of paranoia and the cynical manipulation of that paranoia for political gain. That’s why people would think that.

There are people who honestly believe NASA had the Apollo 1 astronauts murdered because they weren’t going to stay quiet about an impending moon hoax. And that the Challenger and Columbia astronauts were murdered as well because they were going to say that you can in fact see stars in space, therefore the Apollo pictures are faked. There are several serious errors in this line of thinking, but it doesn’t matter — if you are sufficiently cynical about the government, you may believe these things simply because they beautifully fit your personal narrative of a scheming, conniving, mustache-twirling conspiracy.

I even met someone who believed all spaceflight was impossible because it’s physically impossible for anything larger than a bullet to exceed the speed of sound. The web of conspiracy needed to explain this belief was vast indeed and also pretty fragile, but since he didn’t take any time to seriously examine it, it survived in his mind.


One thing to keep in mind with CT scans is that the radiation exposure involved is on the high side (if I recall correctly).

You’re quite right, I neglected to mention the risks of the CT itself. Any x-ray does increase the risk of cancer by a small but finite amount, and CT’s are essentially lots of x-rays.

Even a simple mammogram, for example, does carry a risk that is small but not zero. I sometimes wonder if this risk isn’t taken as seriously as it should – <a href=""John Gofman argued that mammograms are a significant cause of breast cancer, and I have not yet seen a convincing rebuttal of his calculations.

Krebiozen – I can only presume either that Calli is correct, or that the people who say these kinds of things suffer some from some form of cognitive bias, or that they are honestly mistaken. Or possibly some combination of the three.

I suppose it’s also possible that the people who say these kinds of things are speaking from superior knowledge, but that’s a slight possibility at best given what we can currently observe and I’d want evidence of that.

Oddly enough, I have recently heard ( via PRN’s Talkback) that SBM is now monolithically labeling DCIS as ‘cancer’ and pressuring patients to persue extreme measures.

As usual this is more illustrative of alt media’s thought processes than of SBM’s.

Calli & M.O’B.,
So, just the usual lunatic fringe then, though that does seem worryingly large these days.

Members of the medical profession would not tolerate having their private practices taken away from them. Not in a million years. Nor would very wealthy people give up their ability to hire a personal physician.

That’s quite funny really. It seems that similar (the same?) people are arguing that SBM is either forcing treatment or denying treatment for the same condition, and either way it is outrageous. Or sinister. Or both.

Good article, and good timing in that today I received a pathology report on a woman who underwent a bilateral breast reduction and it turns out she has lobular carcinoma in situ in one breast. Looking it up, I see estimates of invasive carcinoma developing in either breast in such a person varying between 4 and 22%, with usual management being regular mammography and palpation for masses. I’m going to have to spoil her day by telling her.

It seems that similar (the same?) people are arguing that SBM is either forcing treatment or denying treatment for the same condition, and either way it is outrageous. Or sinister. Or both.

What, you’re expecting intellectual consistency from conspiracy theorists?

No matter what the actual facts are, they tend to find a way to interpret them as evidence for their theory. Death panels? Evidence that Big Government is out to get you. Death panels don’t exist? Evidence that Big Government is covering up its plan to get you. Either way, it’s all part of the Sinister Plan.

@ Eric Lund:

It seems that most of what I observe attempts to undermine sources of information that are *usually* considered trustworthy- professionals and their associations, universities, governments, media,
in order to give more creedence to their own informationand themselves.
They spend a lot of time castigating ‘authorities’ as prep.

It is often of the form-
show an instance where (a newpaper, television news, medical consensus, governments) were wrong
then, generalise that to more pertinent data.

Sometimes they have to troll back to Semmelweis or tart up more recent material.
e.g. The Times ( both) or governments ( several) or SBM were wrong about ……
so don’t believe them about vaccines/cancer/ SMI/ hiv.

This is endless and never forget that their fans read them repeatedly which drives the message home:
frequency, intensity, duration.

It seems that most of what I observe attempts to undermine sources of information that are *usually* considered trustworthy- professionals and their associations, universities, governments, media,
in order to give more creedence to their own informationand themselves.

That is definitely the case, and it isn’t limited to alt-med types. Global warming denialists (Remember the scientists who were predicting an imminent ice age in the 1970s? If not, then good, because they’re figments of denialists’ imagination.), 9/11 truthers, birthers, and many others use this technique. The Galileo gambit is part of it–yes, the Church circa 1612 was wrong about cosmology, and this is considered evidence we shouldn’t trust authority. The internet has made conspiracy mongering easier than ever before, because these folks can reach their audience without being interrupted by people who point and laugh at them.

Actually, it might be cool to be on a Death Panel. Think of the possibilities for revenge:

“You stole my lunch money in Grade Six. No chemo for you!”

Eric Lund @19 — Well-said!

The global warming denialists, of course, have raised distrust of authority to a high art, largely by adopting the age-old tactic of the smear campaign. The so-called “Climategate scandal” was a straight-up smear campaign, yet many of the simple folk out there are absolutely sure that scientists lied and hid their data in the service of some preposterous greenie leftist conspiracy. Some versions of this must surely involve black helicopters.

“the idea that premalignant diseases inevitably progress to life-threatening cancer is deeply embedded not only in the popular concept of cancer, but in the medical profession itself.”

I think one problem is that it doesn’t have to be inevitable – even someone who’s aware that the probability is low can still conclude that for a large enough sample size, less screening must mean *some* deaths which could have been avoided.

If you take the view that you can’t put a price on a life, then that logic seems appealing. Perhaps, then, the cognitively difficult part is recognizing that (a) the time, money and resources spent on unnecessary treatment could instead be used to save *more* lives elsewhere, and (b) overtreatment itself carries risks, including some risk of death – usually small but nonzero, and potentially larger than the risk associated with leaving carcinoma in situ untreated.

I’m surprised to read that the double mastectomy wouldn’t reduce cancer risk, since it seems to have become quite recommended for brca carriers.
Maybe orac means that as here the cancer risk was very low, mastectomy was not *required* to reduce cancer risk, and would likely have no effect.

@Krebiozen : John Gofman here is using the LNT assumption at low dose on a large population to calculate hypothetic cancer risk. He misses one strong argument against doing that, it’s that the obtained number is not falsifiable. The calculation may result in thousands of estimated death, but at such a low rate that nobody can design a study that either proves or disproves whether those deaths really occur or not, given the size of the population required, as well as the difficulty of evaluating precisely enough the possible confounding factors. Thinking those deaths really occur is effectively an act of faith about something that has no measurable epidemiological impact. Maybe they really exist, but anything else that actually can be measured and confirmed is much more significant.

There’s a quite good summary of the pro and anti LNT at low dose arguments in this IARC document :
P125 has also some interesting discussion of the uncertainties in the actual dose for each examination (and the dose today is likely much smaller than in Gofman’s document).

There exist newer data about repair mechanisms, non linearities, individual variations, but it doesn’t really change the debate. It’s still too small to measure directly, they are many mechanisms that plausibly would lead to a non linear effect instead, but there could also have be surprising and unexpected amplifying effects. So there’s still good reasons to use it as a precautionary principle, but taking care of not basing scaring prediction on it, which would then not be precautionary at all.

@palindrom : it would great to not see the same greenie who defend Global warming use exactly the same strategies as the denialists when it comes to the effects of low radiation doses.

I’m surprised to read that the double mastectomy wouldn’t reduce cancer risk, since it seems to have become quite recommended for brca carriers.

Actually, I said that double mastectomy won’t reduce the risk of dying of breast cancer in women who don’t have BRCA mutations. Also, it certainly won’t detectably reduce the risk of dying of breast cancer in women with average breast cancer risk. That’s a different thing than saying that double mastectomy won’t reduce breast cancer risk.

I had a CT scan not too long ago, and ever since I’ve been concerned about the risk from the radiation exposure. As I understand it, a CT scan uses narrow “pencil” beams of X-rays to make an image. Is the standard for estimating risk from exposure to a CT scan based on the much more diffuse exposure to older conventional X-rays? It seems to me that if the risk from a concentrated narrow beam is estimated based on the risk from a diffuse exposure, the risk is greatly underestimated. It’s like the sunlight falling on a sheet of paper outdoors won’t set it on fire, but the same sunlight concentrated by a lens on a small spot will set it on fire.

Thanks for the link. That’s more or less what I had concluded, but I still find it a little discomforting that Gofman’s hypotheses are unfalsifiable.

There are similar concerns about the effects of Chernobyl, with estimates of deaths covering a vast range, with some claiming it has done people some good through hormesis, and others estimating millions of deaths from additional cancers over the whole of Europe and beyond, which are difficult to detect against background deaths. These disparate estimates depend largely on the political motivations of the estimators, or so it seems to me. I suppose uncertainty is always exploited like this.

Mark Thorson,

It’s like the sunlight falling on a sheet of paper outdoors won’t set it on fire, but the same sunlight concentrated by a lens on a small spot will set it on fire.

I don’t think that’s the best way to think of it. Radiation causes cancer by hitting and damaging a piece of DNA in such a way that it can’t be repaired and that makes the cell cancerous. A dose of radiation spread over a larger area of the body is just as likely to randomly damage a sensitive bit of DNA as the same dose concentrated on a smaller area.

A single electron track from a single x-ray photon has enough energy to damage a DNA strand and cause cancer, it’s just very unlikely to hit any DNA, and even less likely to hit a vulnerable bit. It isn’t radiation insensity per se that causes cancer, just an increase in the likelihood of it doing some damage that starts cancer.

So you’re saying a single hit on DNA is what promotes it to cancer? I thought it was multiple DNA defects in the same cell which promotes a cell to cancer. That’s not true?

So you’re saying a single hit on DNA is what promotes it to cancer? I thought it was multiple DNA defects in the same cell which promotes a cell to cancer. That’s not true?

It’s actually a bit more nuanced than this. Every cell in your body contains 2 copies of BRCA1 and 2. Both of these copies must be broken for a cell to become cancerous. Nobody is born with 2 broken copies of BRCA 1 or 2, as this is embryonic lethal. People who are heterozygous (i.e. have inherited one broken copy of BRCA1) have cells with only one working copy. That’s why it only takes a single somatic, i.e. non-inherited, mutation in BRCA1 for a cell to become cancerous.

Students are often confused by this concept, as it takes 2 broken copies to cause disease (like a recessive disorder), but familial BRCA1/2 breast cancer risk as a trait is dominant.

That blogger at Forbes is an apologist for the Republican Party which is still pandering to the far-to-the-right Tea Party arm of their party. They attempted a complete Government shutdown with their failure to agree to the raising of the Federal debt limit. Their agenda still is to defeat the ACA because they “want to keep government of their healthcare”. Odd, isn’t it, how some of elderly, who are on Medicare and Medicaid support the Tea Party?

Ted Cruz may have broken some crockery on both sides of the aisle…but he will eventually destroy the Tea Party.


So you’re saying a single hit on DNA is what promotes it to cancer? I thought it was multiple DNA defects in the same cell which promotes a cell to cancer. That’s not true?

I’m out of my depth here, but I believe it can be either. When an x-ray photon hits a the nucleus of a cell it generates a high energy electron which tracks across the nucleus until it hits a molecule, perhaps DNA, knocking an electron off it and generating a free radical that can cause more damage. So a single x-ray photon can damage both strands of DNA, making repair impossible, and DNA repair mechanisms are not 100% effective, so even a single hit to a single strand can cause cancer, theoretically. Increased dose and therefore multiple hits increases the risk of lethal damage, of course.

I thought it required several DNA defects, not usually just one, to promote a cell to cancer. You’d be far more likely to get that in a single cell from a concentrated X-ray beam than the same X-ray dose spread out over the whole body. My concern is that the acceptable X-ray dose for a CT scan might be determined based on studies of conventional X-ray exposure. Has the risk of concentrated X-rays vs. diffuse X-rays been evaluated?

I particularly liked, if that’s the word for it, the commenter who was so sure that the government is trying to stop paying for their health care that they are arguing for shutting the government down so it can’t pay for anything, including health care.

Mark Thorson,

My concern is that the acceptable X-ray dose for a CT scan might be determined based on studies of conventional X-ray exposure. Has the risk of concentrated X-rays vs. diffuse X-rays been evaluated?

I think this is taken into account when calculating doses – there are several different measures of radiation exposure that I have never been able to get straight in my head (for example rads are a measure of dose per mass of tissue) , so I’m not entirely sure. Anyone?

I really wouldn’t waste too much energy worrying about this. The risks are so small that measuring the effect of x-rays against the noise of the background cancer rate is very difficult if not impossible.

According to the document jmdesp linked to:

It may be noted that about twice as many medical X-ray examinations are performed in France as in the United Kingdom, and effective doses for medical X-
rays in France are among the highest in industrialized countries.

I was hoping that French cancer rates were no higher than the UK and other countries, but they are about 10% higher than in the UK (about the same as the US). Now I’m worrying about the 3 CTs I have had of my sinuses over the last ten 6 years – thanks Mark!

By “the last ten 6 years” I mean over a period of six years starting ten years ago, obviously. I need sleep.

I’m out of my depth here, but I believe it can be either.

Yes, this is absolutely true, but the chance of acquiring two somatic mutations that break a cell in a way that causes cancer is much lower than just a single such mutation. So yes, for tumor supressor genes like BRCA1/2, the 2-hit model is valid, but in the case of inherited risk variants you only need to acquire a single additional hit, as you’ve already been born with one.

Krebs and Mark:
Most cancers require multiple hits at specific locations in oncogenes and/or tumor suppressors to transform to cancer. People who inherit p53 mutations or retinoblastoma mutations are part-way there and require fewer additional mutations. As Krebs points out, double-strand breaks have a good chance of being repaired erroneously (especially if there is an underlying defect in homologous recombination which repairs more accurately than other types of non-homologous repair).

BRCA mutations cause defects in homologous repair. Incidentally, I’ve never been able to understand why BRCA1/2 mutations have effects that are largely restricted to breast and ovarian tissue. Other defects in homologous recombination have different spectra of malignancies– e.g. Fanconi Anemia.

Incidentally, I’ve never been able to understand why BRCA1/2 mutations have effects that are largely restricted to breast and ovarian tissue

This is still a wide open question in the field, and there really aren’t any great hypotheses out there. For a while it was thought that BRCA1/2 defects caused errors in x-inactivation, which somehow led to the preferential development of breast/ovarian cancer, but the evidence was not very strong and this idea has largely faded from the literature.

Thank you for sharing the Gofman link. I hadn’t seen this before and find it very interesting. I actually looked through his chapters and chapters of back of the envelope calculations to see how he came up with his claim that mammogram cause 75% of breast cancers. First, note that this claim is quite remarkable especially given the clinical evidence that mammograms save lives. and the lack of a 4-fold increase in incidence of invasive breast cancer since adoption of widespread mammographic screening in the 1980’s.

So I couldn’t resist perusing these chapters. The key one is actually #40 which actually lists the assumptions for the conversion of how many cases of breast cancers will occur to each rad delivered. Here they are:
-LNT model (as noted above). This assumption is critical to allow estimates based on much higher doses of radiation experienced by Japanese atom bomb survivors.
-Supralinearity. So actually not quite LNT above say 5 rad. The assumption here is that dose-response curve is 2-2.4x steeper at low doses than at high doses. Some empirical evidence is cited to support this model but the data displayed could be fit pretty well with a straight line. Moreover, the assumption seems to ignore biology of repair mechanisms which can operate better with fewer DNA lesions (the reason treatment radiation is fractionated).
-assumes mammograms starting at age 30 and done annually. Age 40 or 50 is more typical
-Assumes a number of additional questionable factors:
(1) medical radiation has 2x more carcinogenic than atom bomb radiation (Xray vs. gamma rays) [author calls this a “ballpark” estimate]
(2) breast tissue is 2.5x more sensitive than the rest of the body to radiation. [author: “first approximation”]
(3) Radiation will have 5.67x greater effect in US women than on Japanese women because this is the difference in breast-cancer specific death rates between the two countries. [“As additional evidence develops, it may point to other ways to handle country-to-country “transport” of observations. “]

I think this 3rd assumption is a doozy since difference in cancer-specific death rates could have to do with a lot more–medically, socially, genetically– than just to sensitivity of radiation.

So the author finds many factors that ultimately inflates his estimates until he reaches the grand conclusion that mammograms cause 75% of breast cancers. This is just not credible.

In the end, it would be nice to do a more accurate calculation of exactly how many cancers are caused by mammograms, if any. Although we could plug in some more reasonable factors than Gofman, it seems like a fruitless exercise when the clinical data show that lives are saved. Yet, the whole concept favors the USPSTF approach of biennial mammogram screening for age 50-70 for women at average risk. This would minimize risks and maximize preventable deaths.


So the author finds many factors that ultimately inflates his estimates until he reaches the grand conclusion that mammograms cause 75% of breast cancers. This is just not credible.

So this is another case of small(ish) errors multiplying to create a large one. Thanks for your analysis – I have been wondering about Gofman’s estimates occasionally for years.

You can find a huge amount of information on the health effects of radiation from an alarmist perspective on the same website if you find this area interesting. This includes whole books, such as Ernest Sternglass’s ‘Secret Fallout’ which I read a few years ago. As so many of those with unconventional views do, Sternglass appears to have cherry-picked data that supported his conclusions while ignoring the rest. I do find the nuclear authorities lack of cooperation and transparency a little concerning though.

I find it amusing that you can find other websites that make the exact opposite claims about radiation i.e. hormesis, the idea that small doses are beneficial. My favorite that I have posted here before is this one which sells radioactive minerals such as Carnotite (uranium ore) as ‘healing stones’.

Claims of either beneficial or unexpectedly deleterious effects from low level radiation both seem to me to be cases of seeing patterns in noise. At the low end of the curve, dose and health effects measurements both become less reliable and it is easier for people to fit them to whatever belief they they already have whereas, as you put it, “the data displayed could be fit pretty well with a straight line”.

I find it amusing that you can find other websites that make the exact opposite claims about radiation i.e. hormesis, the idea that small doses are beneficial.

Yes, remember Radiothor?. As you say when you are dealing in noise, you can come up with any conclusion you wish.

I do find the nuclear authorities lack of cooperation and transparency a little concerning though.

It must be difficult for authorities to deal with folks like Gofman who reach a conclusion based largely on speculation, then adhere to it despite data to the contrary. Yet, I agree that more transparency is in general a good thing.

Yes, remember Radiothor?.

I’d never heard of it – fantastic. At last, a practical solution for the coming Zombie Apocalpyse! “A Cure for the Living Dead”! I shall sleep easier tonight.

@ MadisonMD #42:

“It must be difficult for authorities to deal with folks like Gofman who reach a conclusion based largely on speculation, then adhere to it despite data to the contrary.”

You are hereby awarded +1 internets for the understatement of this comment thread. 😀

My concern is that the acceptable X-ray dose for a CT scan might be determined based on studies of conventional X-ray exposure. Has the risk of concentrated X-rays vs. diffuse X-rays been evaluated?

I think this is taken into account when calculating doses – there are several different measures of radiation exposure that I have never been able to get straight in my head (for example rads are a measure of dose per mass of tissue) , so I’m not entirely sure. Anyone?

I looked at the calculation of the CTDI briefly last night, and I get the impression that there’s not much more going on than integrating along each slice with a term added for a scatter flux into adjoining slices. This gets complicated by beam shape and weightings for tissue type, which I’m not awake enough to sort out, but as to Mark’s question, yah, it’s been studied. Stochastic effects are more important than direct DNA damage. The “lens on a small spot” analogy isn’t that good a fit, though, because modern CT uses fan beams.

I remember Gofman from the 1990s. He was treated as a cult hero by the anti-nuke crowd. It seemed kind of obvious at the time that he had long since decided that radiation is bad bad bad, and therefore mammography had to be worse than not doing it at all. Another guy who had done some reasonably credible work connecting gulf coast petrochemical plants to health outcomes later tried to connect breast cancer to the existence of nuclear power plants.

One point about children who are born with one missing or deficient copy of the Rb gene: This means that they have only a single working copy in every cell. That means that any one cell (out of billions) that gets a hit on the working copy is then without the anti-oncogenic protection of an Rb gene product.

Another point is that some genetic problems lead to an accelerated accumulation of mutations in surviving cells, leading to the acceleration of weirdness that characterizes advanced cancer cells. There are DNA repair systems and there are systems that prevent the cell from surviving (or at least dividing) if some problem is detected during mitosis. For example, normal cells can detect a problem involving the chromosomes not lining up properly prior to being pulled to opposite ends of the cell. A deficiency in this system can lead to problems.

To follow up on an earlier comment, homozygous loss of function BRCA-1 mutations are believed to be lethal because there are no reports of any such patients.

Patients with homozygous BRCA-2 mutations have a form of Fanconi anemia. This was a huge surprise when the researchers working to isolate the Fanconi anemia gene discovered that BRCA-2 was responsible for some of those cass.

It’s a funny coincidence that this topic has come up today of all days…I’m at the American Society of Human Genetics meeting this week, and the first session I’m going to tomorrow is on this very subject. I’ll report back with the latest on this tomorrow!

Yes, lease do. I have a personal interest in that subject. If you are willing, I’d like to take a look at any electronic handouts that you have.

Adam and Dr. Mike,
Thank you for sharing this information about homozygous versus heterozygous BRCA phenotypes, and that BRCA2 homozygotes have Fanconi. I’d also welcome further info from ASHG from AdamG on this topic.

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