Respectful Insolence

The last couple of weeks, I’ve made allusions to the “Bat Signal” (or, as I called it, the “Cancer Signal,” although that’s a horrible name and I need to think of a better one). Basically, when Bat Cancer Signal goes up (hey, I like that one better, but do bats get cancer?), it means that a study or story has hit the press that demands my attention. It happened again just last week, when stories started hitting the press hot and heavy about a new study of mammography, stories with titles like Vast Study Casts Doubts on Value of Mammograms and Do Mammograms Save Lives? ‘Hardly,’ a New Study Finds, but I had a dilemma. The reason is that the stories about this new study hit the press largely last Tuesday and Wednesday, the study having apparently been released “in the wild” Monday night. People were e-mailing me and Tweeting at me the study and asking if I was going to blog it. Even worse, the PR person at my cancer center was sending out frantic e-mails to breast cancer clinicians because the press had been calling her and wanted expert comment. Yikes!

What to do? What to do? I wanted to jump right ahead and blog it immediately here, as my more “Insolent” persona. On the other hand, this was big. This was serious. Above all, this was about something directly relevant to my clinical specialty. Those of you who follow me both here and at my non-pseudonymous blog know that I tend to like to save things that are big, serious, and directly relevant to my clinical specialty for that blog, with a crosspost here. Oh, hell, I crosspost almost all of my posts published there sooner or later because I don’t want to waste material. In a way I’m glad I waited. The reason is that it gave me time to cogitate and wait for reactions, which is always more fun.

Mammograms don’t save lives, quoth the BMJ (and everyone covering the study)!

After my obligatory navel-gazing explanatory introduction that infuriates some and entertains others, let’s jump into the study itself. It was published in the BMJ and is, as the title tells us, the Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial. Before we delve into the findings, I should take a moment to explain what the Canadian National Breast Screening Study (CNBSS) actually is. The first thing you need to know is that this study has been contentious since its very beginning. In particular radiologists have been very critical of the study. One radiologist in particular, whom we’ve encountered before, pops up time and time again in articles critical of the CNBSS. This doesn’t mean that the criticisms of the study aren’t invalid, but this particular radiologist, given his track record, did send up a red flag regarding critics of this study, given some of the truly badly thought out criticisms he’s leveled at other mammography studies, most notably about a year ago.

The study, conceived in the late 1970s and begun in 1980, the CNBSS was a randomized clinical trial that was designed to answer two questions, depending upon the age group: (1) to compare regular breast examination to breast examination plus screening mammography (age 50-59) and (2) compare screening mammography plus “usual care” (age 40-49). These were questions that had arisen from the only existing large study published at the time, the New York Health Insurance Plan (HIP) Study, which in 1963 had randomized (without informed consent) women between the ages of 40 and 64 such that around 30,000 received annual two-view mammography and clinical breast examination for three screens, with another 30,000 serving as controls who received “usual care” (i.e., clinical breast examination). The results, first published in 1977, indicated a statistically significant reduction in breast cancer mortality of 23%. However, no benefit was seen in the 40-49 year old age group. Also, over an eight-year period after diagnosis, breast cancer cases that were positive only on mammography when screened had a case fatality rate of 14%, compared to 32% for cases positive only in the clinical examination and 41% for cases positive on both modalities. The thought at the time was that the reason no difference was seen in younger women was because the incidence of breast cancer is so much lower in women aged 40-49 than it is in women aged 50-64. As I’ve discussed many times before, the less common a disease is in a population being screened, the more false positives there will be and the harder it will be to detect a decline in mortality from that disease due screening because the smaller (on an absolute basis) any such decline will be. That’s almost certainly why the early mammography studies that led to the implementation of widespread mammographic screening programs for the most part were unable to demonstrate a benefit in terms of preventing death from breast cancer in women under 50.

In any case, the HIP Study had raised the question of what the incremental benefit of screening mammography was over “usual care,” which included, in most cases, regular visits to one’s primary care doctor and breast self-examination, described in the introduction to the study reported last week thusly:

In 1980 a randomised controlled trial of screening mammography and physical examination of breasts in 89,835 women, aged 40 to 59, was initiated in Canada, the Canadian National Breast Screening Study.4 5 6 7 It was designed to tackle research questions that arose from a review of mammography screening in Canada8 and the report by the working group to review the US Breast Cancer Detection and Demonstration projects.9 At that time the only breast screening trial that had reported results was that conducted within the Health Insurance Plan of Greater New York.10 11 Benefit from combined mammography and breast physical examination screening was found in women aged 50-64, but not in women aged 40-49. Therefore the Canadian National Breast Screening Study was designed to evaluate the benefit of screening women aged 40-49 compared with usual care and the risk benefit of adding mammography to breast physical examination in women aged 50-59. It was not deemed ethical to include a no screening arm for women aged 50-59.

So basically, there were two parts to this study: Mammographic screening plus regular clinical breast examination versus usual care in women aged 40-49 and mammographic screening plus regular clinical breast examination plus regular clinical breast examination alone in women aged 50-59. Here’s the study schema:

0

Women with any abnormal findings, be it on physical examination or mammography, were referred to a special review clinic directed by the surgeon affiliated with the study center, where, if indicated, diagnostic mammography was performed. (This study was carried out at 15 screening centres in six Canadian provinces, located in teaching hospitals or in cancer centers). I deem it important right here to emphasize yet again that all of these mammography studies were carried out in asymptomatic women (i.e., women who didn’t have any symptoms or lumps in their breasts). The reason I consider it important is that screening and diagnostic mammography are frequently confused in the minds of the lay public, and there is no controversy about what a woman who detects a lump in her breast or whose doctor detects one should do: Get it checked out with diagnostic mammography and (often) ultrasound, sometimes complemented with MRI. That’s the difference between diagnostic and screening mammography. Diagnostic mammography is done with the intention of working up an abnormality found on physical examination or screening mammography to determine if it needs to be biopsied. Pontification thus ended, I now point out that women who needed biopsies got them done by a surgeon to whom their primary care doctor referred them, and women who were thus diagnosed with cancer underwent treatment by surgeons and oncologists chosen by their primary care doctor.

Study subjects who enrolled had a physical examination (clinical breast exam) and were taught breast self-examination by trained nurses. Then they were randomized according to the schema above as described in the protocol:

Irrespective of the findings on physical examination, women aged 40-49 were independently and blindly assigned randomly to receive mammography or no mammography. Those allocated to mammography were offered another four rounds of annual mammography and physical examination, those allocated to no mammography were told to remain under the care of their family doctor, thus receiving usual care in the community, although they were asked to complete four annual follow-up questionnaires. Women aged 50-59 were randomised to receive mammography or no mammography, and subsequently to receive four rounds of annual mammography and physical examination or annual physical breast examinations without mammography at their screening centre.

In reporting the results, the investigators refer to the mammography plus breast physical examination arm in both age groups as the mammography arm, and the no mammography arms (usual care for women aged 40-49 and annual breast physical examinations for women aged 50-59) as the control arm. Also, the study is often referred to in two ways. The arm for women aged 40-49 is often referred to as CNBSS-1, and the arm for women aged 50-59 is often referred to as CNBSS-2. Just to make that clear.

So let’s get to the results. But before I do, let’s look at the last times the results were reported for this study, the 13 year followup in 2000 for CNBSS-2 and the 11-16 year followup in 2002 for CNBSS-1. The first report on CNBSS-2 showed no difference in breast cancer-specific mortality between the two groups in women aged 50-59; actually, the numbers showed slightly more deaths in the screening group, but that difference was nowhere near statistically significantly different. Although there was an unwritten assumption that there was likely to be a benefit to the addition of mammographic screening that just hadn’t shown up yet because the followup time was too short, the authors were forced to conclude that “our estimates of effect exclude a 30% reduction in breast cancer mortality from mammography screening” and that “chance is an unlikely explanation for our findings.” In the second study reporting the results for CNBSS-2, the investigators concluded:

After 11 to 16 years of follow-up, four or five annual screenings with mammography, breast physical examination, and breast self-examination had not reduced breast cancer mortality compared with usual community care after a single breast physical examination and instruction on breast self-examination. The study data show that true effects of 20% or greater are unlikely.

In other words, as of 2002, no benefit to adding mammography to routine care in women under 50 or to regular clinical breast examination in women 50-59 had yet been observed. The current study, unfortunately, completes the trend. Here’s the graph of all cause mortality (all deaths of study participants):

F2.medium.gif

And here’s the graph for breast cancer-specific mortality (women who died of breast cancer)

F3.medium.gif

As you can see, the curves line up almost exactly. There is no statistically significant difference. There’s not even a whiff of a hint of a statistically significant difference.

Now that the data are more mature, the investigators could do what they couldn’t do before, namely to make an estimate of how much overdiagnosis was occurring in the study. (Overdiagnosis is the detection of disease that doesn’t need to be treated, disease that would never progress within the lifetime of the patient to endanger her life.) The authors noted that at the end of the screening period, there was an excess of 142 breast cancer cases in the mammography arm compared to the control arm (666 versus 524). By fifteen years after enrollment, the excess became constant at 106 cancers, which was 22% of all screen-detected breast cancers. Because the mortality rates were the same between the mammography versus control groups, these cancers represent overdiagnosis.

One notes that this number is remarkably similar to the estimates of overdiagnosis found in other clinical trials and epidemiological studies of mammography that I’ve discussed over the years. For example, way back in 2008, I discussed a study that suggested that 22% of breast cancers detected by screening mammography spontaneously regress.

Whoa. Maybe I shouldn’t have been so skeptical of that result when I wrote it up. And I’m not alone in noting how strikingly similar this number is to the rate of overdiagnosis in other studies. In an accompanying editorial, Kalager et al note the same thing, pointing out that “the amount of overdiagnosis observed in the previous randomised controlled trials is strikingly similar (22-24%).” Of course, there are others, many other studies, and in fact the 22% estimate is rather at the low end of some of the more recent studies. For example, the most recent “blockbuster” mammography study estimated the rate of overdiagnosis to be between 22% and 36%, depending upon the parameters used in the investigators’ model. One study that I discussed even suggested that one in three mammography-detected cancers were in fact overdiagnosed and overtreated, and I said:

Don’t get me wrong. There is no doubt that mammographic screening programs produce a rate of overdiagnosis. The question is: What is the rate? Unfortunately, the most accurate way to measure the true rate of overdiagnosis would be a prospective randomized trial, in which one group of women is screened and another is not, that follows both groups for many years, preferably their entire life. Such a study is highly unlikely ever to be done for obvious reasons, namely cost and the fact that there is sufficient evidence to show that mammographic screening reduces breast cancer-specific mortality for women between the ages of 50 and 70 at least, the latter of which would make such a study unethical. Consequently, we’re stuck with retrospective observational studies, such as the ones analyzed in this systematic review.

Well, the CNBSS is a randomized trial that follows women for their entire lives. Whatever its flaws (which will be discussed in the next section as I try to put it into context), it’s about as close to what I wanted four and a half years ago as we’re ever likely to get, which means that an overdiagnosis rate of somewhere around 20% or so is probably about as good an estimate of overdiagnosis of breast cancer by screening mammography as we’re ever likely to get. The problem, of course, boils down to two issues. First, we can’t tell which cancers diagnosed by screening mammography are overdiagnosed; i.e., which ones will never progress within the lifetimes of the women for whom they’re detected to endanger their lives. That leaves us a mandate to treat them all. Second, there is the question of whether this level of overdiagnosis is “worth it” for the level of benefit in reducing breast cancer mortality provided by screening mammography. The first problem, of course, can be solved by better predictive tests to separate the nasty players from the overdiagnosed players, but the second question is not so easy to answer.

Another important point is that this is the only large randomized study reported in the era of effective multimodality therapy with surgery, adjuvant chemotherapy regimens (chemotherapy administered after initial treatment to reduce the risk of recurrence), adjuvant Tamoxifen (Tamoxifen blocks the action of estrogen and can be used to decrease the risk of recurrence of tumors that respond to estrogen), and radiation therapy. This brings up the question of whether the reduction in mortality from breast cancer that we have observed since 1990—contrary to what you frequently hear, mortality from breast cancer is indeed falling and has been falling since around 1990—is primarily due to better treatment rather than earlier detection. There have been studies published over the last five years that suggest that this might be the case. But is it?

The knives come out, allowing me to (try to) put it all into context

Predictably, as always happens after a study like this, the knives came out, mostly wielded by radiologists. As is often commonly the case, the criticisms were a mixture of the reasonable, the ridiculous, and the obviously turf-protecting. What’s depressing about many of the criticisms of the study is that too many of the people making them seem unaware (or seem to deny) some very basic concepts about screening, namely overdiagnosis, overtreatment, lead time bias, and length bias. I’ve discussed them all before on multiple occasions, pointing out that the early detection of cancer does not always result in improved survival, and more sensitive tests can often lead to upstaging and more aggressive therapy without benefit. I’ve discussed overdiagnosis already. Lead time bias is a situation where early detection of the cancer doesn’t result in improved survival but only appears to do so because the disease is detected earlier and the patient lives longer with it. The best explanation of overdiagnosis (besides mine, of course) I’ve ever found can be read here. Length bias simply describes the tendency of screening to detect more slowly growing, indolent tumors. These problems have led to a major rethinking of prostate cancer screening and is beginning to do the same for breast cancer screening.

Indeed, the 15-25% reduction in breast cancer mortality cited by mammography proponents translates to an absolute risk picture in which averting one death from breast cancer with mammographic screening for women between the ages of 50-70 requires screening 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 ductal carcinoma in situ (DCIS). As reported in the New York Times treatment of this study, approximately 1 in 424 women in the CNBSS received unnecessary cancer treatment. In other words, mammographic screening is very labor- and resource-intensive, and a lot of women have to be screened to save one life. As I’ve also said many times in the past, whether this is “worth” it is more a value judgment than a scientific judgment, although that value judgment has to be informed by accurate science.

Of course, the CNBSS is not without shortcomings. Indeed, it’s been attacked nearly from its earliest reports, mostly by radiologists. Indeed, it’s instructive to peruse the criticisms posted after the article (one advantage of BMJ journal articles). They range from the reasonable to real howlers. For example, not surprisingly, Daniel B. Kopans, a professor of radiology at the Harvard Medical School and someone who’s well known for attacking any study that questions mammography, particularly after the USPSTF guidelines were published in 2009 and who earlier gave us this howler:

This is simply malicious nonsense,” said Dr. Daniel Kopans, a senior breast imager at Massachusetts General Hospital in Boston. “It is time to stop blaming mammography screening for over-diagnosis and over-treatment in an effort to deny women access to screening.”

He was referring to H. Gilbert Welch’s study published in late 2012 in the New England Journal of Medicine that found a high degree of overdiagnosis due to mammography. As I pointed out at the time, Dr. Kopan was completely wrong, and overdiagnosis as a pitfall of screening programs exists. He’s also known for saying things like this in about the members of the USPSTF task force that to the USPSTF recommendations published in 2009:

I hate to say it, it’s an ego thing. These people are willing to let women die based on the fact that they don’t think there’s a benefit.

It’s therefore not surprising that after the BMJ article, Dr. Kopans makes the same sorts of statements, statements echoed in an article entitled We do not want to go back to the Dark Ages of breast screening, by Dr. László Tabár and Tony Hsiu-Hsi Chen, DDS, PhD published on AuntieMinnie.com, described as providing “the first comprehensive community Internet site for radiologists and related professionals in the medical imaging industry” and in a statement on the American College of Radiology website. Many of the criticisms are shared, although Dr. Tabar does appear to me a bit disingenuous when he says that “Canadian trials could not evaluate the independent impact of mammography because of the confounding effect of physical examination.” I suppose that’s why they compared physical examination to physical examination plus mammography in the 50-59 year old group.

Dr. Kopan’s first criticism was that the quality of the mammograms was below state of the art, even for the 1980s. Indeed, Dr. Kopans has made these arguments before for the last 24 years. However, as has been pointed out, the purpose of the CNBSS was to examine whether the addition of mammography added anything to breast cancer screening and resulted in decreased mortality from breast cancer using community-based settings, in other words, using mammography as it was practiced in the community. Moreover, as others have pointed out, the quality of mammography increased over time. In any case, this and many of the criticisms leveled by Dr. Kopans and others have been fairly convincingly refuted CNBSS investigator Cornelia J. Baines, the latter of whom published an article entitled Rational and Irrational Issues in Breast Cancer Screening and by an article in which Kopans himself was a coauthor, which showed that, although only 50% of mammograms had satisfactory image quality in 1980, by 1987 85% were judged to have satisfactory quality.

Perhaps the most serious charge made by Dr. Kopans is that there was misallocation of nastier cancers to the control arm. In other words, he charges:

In order to be valid, randomized, controlled trials (RCT) require that assignment of the women to the screening group or the unscreened control group is totally random. A fundamental rule for an RCT is that nothing can be known about the participants until they have been randomly assigned so that there is no risk of compromising the random allocation. Furthermore, a system needs to be employed so that the assignment is truly random and cannot be compromised. The CNBSS violated these fundamental rules (6). Every woman first had a clinical breast examination by a trained nurse (or doctor) so that they knew the women who had breast lumps, many of which were cancers, and they knew the women who had large lymph nodes in their axillae indicating advanced cancer. Before assigning the women to be in the group offered screening or the control women they knew who had large incurable cancers. This was a major violation, but it went beyond that. Instead of a random system of assigning the women they used open lists. The study coordinators who were supposed to randomly assign the volunteers, probably with good, but misguided, intentions, could simply skip a line to be certain that the women with lumps and even advanced cancers got assigned to the screening arm to be sure they would get a mammogram. It is indisputable that this happened since there was a statistically significant excess of women with advanced breast cancers who were assigned to the screening arm compared to those assigned to the control arm (7). This guaranteed that there would be more early deaths among the screened women than the control women and this is what occurred in the NBSS. Shifting women from the control arm to the screening arm would increase the cancers in the screening arm and reduce the cancers in the control arm which would also account for what they claim is “overdiagnosis”.

Make no mistake, Dr. Kopans is accusing the investigators running the CNBSS of scientific fraud here. I’m surprised he’s so bold about it. You’d think he’d have strong evidence to back up this charge. You’d be wrong. If what Dr. Kopans said were true, then the Canadian government should be going after the investigators. The authors themselves are aware of this charge and even answered it in their article:

We believe that the lack of an impact of mammography screening on mortality from breast cancer in this study cannot be explained by design issues, lack of statistical power, or poor quality mammography. It has been suggested that women with a positive physical examination before randomisation were preferentially assigned to the mammography arm.12 13 If this were so, the bias would only impact on the results from breast cancers diagnosed during the first round of screening (women retained their group assignment throughout the study). However, after excluding the prevalent breast cancers from the mortality analysis, the data do not support a benefit for mammography screening (hazard ratio 0.90, 95% confidence interval 0.69 to 1.16).

I actually agree with Dr. Kopans on this one point: Only women with no physical findings should have been randomized to screening mammography. That is perhaps the biggest flaw in the design of the CNBSS. However, excluding women diagnosed with a cancer on the first round of mammography, as the authors argue, and finding no difference in breast cancer mortality do rather argue that it probably didn’t make a difference. The author also points out that another criticism, apparently leveled by Siddhartha Mukherjee in The Emperor of All Maladies, that the women in the mammography group were somehow at a higher risk for cancer. The authors point out that breast cancer was diagnosed in 5.8% of women in the mammography arm and in 5.9% of women in the control arm (P=0.80), showing that the risk of breast cancer was the same in both groups. Finally, there were reasons for why the allocation was done the way it was, and the explanation was not unreasonable;

Randomization was performed by the center coordinators after nurse examiners had clinically examined the participants. Center coordinators were blind to the results of the breast examination.

What in fact was the situation vis-a-vis randomization?

Most tellingly there was no incentive for screening personnel to subvert randomization. The CNBSS protocol required that anyone with an abnormal finding on CBE [clinical breast examination] had to be referred to the study surgeon who would order a diagnostic mammogram when clinically indicated. Symptomatic women require diagnostic mammography, not screening mammography. It was not necessary to “place” as claimed [24] clinically positive participants in the mammography arm of the study in order for them to get a mammogram.

In the CNBSS there were more than 50 variables (demographic and risk factors) which were virtually identically distributed across control and study groups, clear evidence of successful randomization [25,26].

That certainly decreases—although it does not completely eliminate—my concern about the original design. There have also been other studies before that looked for evidence of subversion of randomization in the CNBSS and have failed to find evidence of nonrandom allocation of patients sufficient to affect the results of the trial. As was pointed out by a commenter after the BMJ article named Rolf Hefti, Dr. Kopans never mentions these studies that disagree with his conclusion, fails to note counterarguments that have been made to his accusations, and disingenuously complains about the low rate of detection by mammograms alone (32%), even though that number is consistent with the rates reported in the 1990s—years after the screening period for the CNBSS.

And so the battle rages on, same as it ever was. What amuses me most about this is the seeming underlying assumption that the CNBSS investigators wanted to find no benefit due to screening mammography. My guess is that they were horribly disappointed at the results. No one does the enormous amount of work and spend the money to do a large multicenter trial involving tens of thousands of women because he wants to end up with a negative study, to the point that he would be willing to mess with the randomization to make it happen. The assumption underlying Dr. Kopans’ accusation is ludicrous.

The bottom line

I’m going to give you my bottom line, although it’s going to sound wishy-washy. Does the CNBSS “prove” that screening mammography is useless? Of course not, not any more than any single study ever could, given such a complex issue as screening for breast cancer. The CNBSS is a flawed study that could possibly be a false negative, such that any true benefit in terms of prevention of breast cancer mortality by mammography is buried in statistical noise. However, it is not nearly as flawed a study as its critics, such as Dr. Kopans and Dr. Tabár, would have you believe, nor is it a fraudulent study, as Dr. Kopans would apparently have you believe. It is the result of a group of investigators doing the best they could with the materials they had based on the knowledge they had in the late 1970s and must be weighed against all the other studies examining mammography finding benefit or no benefit. Moreover, it is not new information. It’s just a longer term followup of results first reported in the early 1990s and last reported more than ten years ago.

That being said, I still think it’s entirely appropriate for the study authors to conclude that “the data suggest that the value of mammography screening should be reassessed.” This isn’t a new conclusion, either. It’s part of an evolution that’s been going on since before the USPSTF released its guidelines back in 2009. You’ll remember that back then I characterized those recommendations, which included not beginning routine mammographic screening until age 50, as “not the final word.” Clearly the CNBSS won’t be the last word, either, but it should be included as part of the evidence base for the reevaluation of mammography screening guidelines.

What doesn’t help is denial that overdiagnosis is a real phenomenon and rejection of the now irrefutable contention that detecting a cancer earlier does not necessarily result in improved survival. There are some who are arguing that because that patients with tumors detected by mammography only in this study had better five year survivals than patients with tumors detected clinically, it means the mammography is worthwhile. That’s a horrible argument, because in reality increased survival as observed in this study is, if anything, evidence in favor of overdiagnosis, an observation that was made, shockingly, in an article published in The Atlantic, given how much nonsense about medicine has been published in that magazine before. As I pointed out before, decreases in mortality, not necessarily improvements in survival, are the gold standard that shows a screening test (as opposed to a treatment) really does work.

Radiologists also argue that imaging technology is so much better today than it was in the 1980s. Even mammography itself is much better. This is undoubtedly true, but better, more sensitive imaging, while it could potentially make modern mammography screening programs more effective in preventing breast cancer, could also greatly exacerbate the problem of overdiagnosis. Overdiagnosis is real, and there are diminishing returns on the detection of cancer. If treatment of screen-detected cancers, adjusted for lead time bias, doesn’t clearly result in improved survival, then there’s a problem.

The point, obviously, is to find the “sweet spot,” which maximizes the benefit of screening and minimizes the harms due to overdiagnosis and overtreatment. Based on current evidence, of which the CNBSS is just one more part, I’m more and more of the opinion that our mammography screening guidelines need to be tweaked and personalized because the current “one size fits all” regimen is probably too aggressive for most women at average risk for breast cancer. It’s an evolution in my thought that’s been going on for years. In any case, in any statement I’d put something in there about determining what the “sweet spot” is for mammography. It’s also reasonable, for now at least, to stick with existing guidelines, with perhaps more of a personalized approach to screening of women between ages 40 and 49. That’s what I intend to do until new evidence-based guidelines emerge. And emerge they will, likely within a year.

ADDENDUM: Dr. Miller’s response to the criticisms leveled at the CNBSS have been published, and he very convincingly put Dr. Kopans and others in their place.

Comments

  1. #1 dingo199
    February 17, 2014

    I am struggling to get a handle on the degree of harm imposed by overdiagnosis. Of course having unnecessary worry, undergoing biopsy or lumpectomy must be very unpleasant, but if I were a female I would feel nothing but a sense of relief if a suspicious mass were found to be benign at the end of the day.
    How does one equate the harms of overdiagnosis in 22% women against the harms of missing a cancer diagnosis in 0.12% of women?

  2. #2 Julian Frost
    Gauteng East Rand
    February 17, 2014

    dingo199, you may want to ask Estelle Kunneke. She was incorrectly diagnosed with cancer, underwent a double mastectomy and chemotherapy, and has now won a R2.8 million damages case against the Limpopo Department of Health.
    http://www.iol.co.za/news/south-africa/limpopo/scarred-by-false-diagnosis-1.1647603

  3. #3 C.C.
    February 17, 2014

    I’m not sure about cancer in bats, but apparently there is already a punk band named Cancer Bats. http://cancerbats.com/

  4. #4 WT
    February 17, 2014

    Sounds like Doctor Kopans is just trying to protect his income here.

  5. #5 Michael Finfer, MD
    February 17, 2014

    Most women who have a lumpectomy also get radiation. That is not without risk. It is something that you would not want to give to a patient for no good reason.

    As I have stated here before, we need some way to recognize the tumors that do not need to be treated. In light of the controversy, annual mammography in this age group is likely to continue for quite some time.

    I am impressed with how the radiologists’ reaction to to this issue resembles the urologists’ reaction to the recommendation to end routine PSA screening for prostate cancer. Redact the names and the words breast and prostate, and I don’t think you could tell the difference.

    I am beginning to have qualms about advocacy, any advocacy. It is beginning to seem to me that many advocates are biased and are unwilling to look at evidence and change their viewpoints accordingly.

  6. #6 Elaine Schattner
    United States
    February 17, 2014

    Seriously David,
    I think you should have been more skeptical of the 2008 report about “overdiagnosis.” Finding an indolent or Stage 0 tumor does not necessarily (and should not) lead to overtreatment, if doctors and patients make reasoned decisions.

  7. #7 Lawrence
    February 17, 2014

    Medical professionals should err on the side of caution & of course, realize that it sometimes means that too much of a “good thing” becomes a bad thing over time.

  8. #8 Irène Delse
    On dry land, among seabirds
    February 17, 2014

    Do bats get cancer? Sure they do, like nearly all living things, with the possible exception of naked mole rats.

  9. #9 Becca Stareyes
    February 17, 2014

    One thing I’m now curious about is if, in the study, women with mammograms had less intensive treatment options required than women without: fewer mastectomies and less chemo. That would be another argument for mammograms. (Though perhaps more of an argument for a choice in screening methods: which do you want more, to treat tumors that will never bother you because we can’t be sure which ones will end up being harmless, or to be more likely to require major surgery to treat a tumor.)

  10. #10 Orac
    February 17, 2014

    Finding an indolent or Stage 0 tumor does not necessarily (and should not) lead to overtreatment, if doctors and patients make reasoned decisions.

    Surgical excision is overtreatment of many such lesions, and nearly all of these are surgically excised. Radiation after surgical excision is overtreatment for many such lesions, and nearly all of these receive radiation. Tamoxifen is overtreatment of a lot of these lesions, and most women with such lesions, if they are estrogen receptor-positive, receive Tamoxifen.

    No, many, many of these indolent DCIS lesions are overtreated because we don’t know how to distinguish between lesions that will progress and those that will not, in other words, because we don’t have the tools to make these “reasoned” decisions.

  11. #11 R Marks
    February 17, 2014

    Do you mind explaining the reasoning behind the following sentence:

    “As I’ve discussed many times before, the less common a disease is in a population being screened, the more false positives there will be, the harder it will be to produce a decline in mortality from that disease by screening”

    I would expect that false negatives affect the mortality rate of the disease. How would an increasing number of false positives make it harder to decrease the mortality rate?

  12. #12 Orac
    February 17, 2014

    Imperfectly worded. Try the new version.

  13. #13 Dangerous Bacon
    February 17, 2014

    “Estelle Kunneke… was incorrectly diagnosed with cancer, underwent a double mastectomy and chemotherapy, and has now won a R2.8 million damages case against the Limpopo Department of Health.
    http://www.iol.co.za/news/south-africa/limpopo/scarred-by-false-diagnosis-1.1647603

    While this story is badly reported, what it _sounds_ like is that a false positive diagnosis was made on the basis of fine needle aspiration cytology (not mammography), and that for some reason bilateral _radical_ mastectomies were performed (which would be massive overtreatment, as such procedures have not been standard of care for a long time). But it’s hard to tell exactly what happened from that story.

  14. #14 Elaine Schattner, MD
    www.elaineschattner.com
    February 17, 2014

    About giving radiation, tamoxifen – I agree with you; they are over-prescribed for early-stage and pre-malignant conditions. But that is overtreatment, not overdiagnosis.

  15. #15 Kay
    Canada
    February 17, 2014

    I have Her2 + metastatic breast cancer. Diagnosed in 2009 at age 57, after I felt a lump, confirmed by my physician, and referred to breast clinic for a biopsy. I have had state of the art follow up scans and treatment, which has nasty side effects and also one good one for me, at this point in my life, I am alive. Prior to my diagnosis I had yearly mammograms.
    I have 3 sisters so I exhorted them to have mammograms as recommended by our Cancer specialists. As a screening test the mammogram is particularly odious. My thinking now is if a mass is felt get a diagnostic mammogram, ultrasound, MRI, whatever. But save the expense to your dignity and the healthcare system for diagnosis. Ditch screening except for high risk women and men.

  16. #16 Orac
    February 17, 2014

    @Elaine: I know the difference between overdiagnosis and overtreatment. The point is that overdiagnosis nearly always leads to overtreatment; the two are inextricably linked. Those overdiagnosed DCIS lesions are almost invariably at least surgically excised and, unless the woman is over 70, treated with radiation and, often, Tamoxifen.

    Or perhaps you can explain how overdiagnosis of DCIS does not lead to overtreatment.

  17. #17 Ren
    February 17, 2014

    “However, after excluding the prevalent breast cancers from the mortality analysis, the data do not support a benefit for mammography screening (hazard ratio 0.90, 95% confidence interval 0.69 to 1.16)”

    They controlled for that potential bias and found no difference in the groups. So they did take it into account, they knew it was there, and they did something about it in the analysis. Yes, it could have been better designed, but it’s pretty darn good.

  18. #18 dingo199`
    February 17, 2014

    Assuming a (false) positive mammogram has resulted, why are the lumpectomy histology results not reviewed before commencing radiotherapy and tamoxifen. Am I just being thick here?

  19. #19 jane
    February 17, 2014

    The 22% overdiagnosis rate is reportedly a substantial underestimate because it included only actual cancers and not DCIS, though the vast majority of DCIS found was surely treated. It’s been sad to see all the women coming out of the woodwork to say that their “lives were saved” by screening mammography that found a tiny spot of DCIS, leading to surgery and radiation [that may eventually cause them to die of heart failure or lung cancer]. OTOH, two different sources have idiotically reported that 22% of all the women screened were overdiagnosed with cancer.

    As for the alleged impropriety of allowing women with lumps in their breasts to be signed up for the study: The large majority of such lumps are benign, and a large percentage of women have benign lumps. (Coffee drinking increases cyclical lumpiness for more than a few women.) Though there’s little evidence that fibrocystic breast “disease” increases cancer risk meaningfully, radiologists and gynecologists occasionally claim that they just know it must. Had all lumpy women been permanently excluded from the study, the claim by radiologists now would have been that “women At Risk” had been excluded, so the results applied only to super-low-risk women and average women should ignore them.

  20. #20 sirhcton
    February 17, 2014

    Don’t you all see the traitorous trend touted here by our host? He is betraying Big Pharma’s partners in the scheme to suck up all our money, Big Surgery and Big Treatment. Not only will his income fall, he will lose his seat on the death panel. Orac must recant! Apostates can not be tolerated.

  21. #21 Orac
    February 17, 2014

    Assuming a (false) positive mammogram has resulted, why are the lumpectomy histology results not reviewed before commencing radiotherapy and tamoxifen. Am I just being thick here?

    Overdiagnosis doesn’t mean false positive. The two are different concepts. Overdiagnosis means that there really is an abnormality there that, by all diagnostic criteria currently used, is cancer or precancerous but it’s a lesion that will never endanger the life or health of the woman. Not all “cancerous” lesions progress rapidly enough to endanger the life of the woman in which they’re found, and some can even regress. The problem is that we can’t predict which will do what, and we have to treat them all as though they will progress and metastasize.

    Also, I want to take this opportunity once again to point out that overdiagnosis being discussed here ONLY applies to cancers detected by mammography alone. It does NOT apply to cancers detected because the woman or her doctor felt a lump. Those cancers generally do progress and only very rarely regress. Women who detect a lump should undergo diagnostic mammography and ultrasound.

  22. #22 Julian Frost
    February 17, 2014

    @Dangerous Bacon, I was aware of that. I was just trying to make the point about how misdiagnosis/overdiagnosis can cause harm.

  23. #23 dingo199`
    February 17, 2014

    Gotcha, orac. Thanks for the clarification.

  24. #24 AC
    February 17, 2014

    #3 – Who happen to be Canadian ;)

  25. #25 Daniel Corcos
    France
    February 17, 2014

    Not sure that the similarity of the curves are only related to overdiagnosis. There could be a benefit for some women, whereas in the same time BRCA carriers would have an increased cancer incidence as a consequence of irradiation.
    https://www.researchgate.net/profile/Daniel_Corcos2/?ev=prf_highl

  26. #26 PA_in_VA
    February 17, 2014

    The biggest question I keep finding myself with when looking at these studies showing no decrease in mortality is whether or not they result in a decreased need for more invasive treatment. In other words, does early mammography result in more women being diagnosed in a stage that is ‘curable’ with lumpectomy, vs requiring mastectomy, node dissection, chemo, radiation, plus (often) tamoxifen at a later stage. I think that is important information to look at before we decide that screening mammograms are of no value. It seems many women would find the difference to be important.

    If mammography results in less invasive (and less expensive) treatment, does that offset the costs of screening mammography and overdiagnosis?

    Just some additional questions I’d personally like to see studied before I come to any firm conclusions one way or another.

  27. #27 Kurt Wagner
    Michigan
    February 17, 2014

    It seems strange that if you had two women come to your medical office, with exactly the same disease, say a 1cm invasive ductal carcinoma, their management would differ greatly depending one whether it was palpable or not, if imaging screening was not also recommended. The patient with a palpable, superficial 1cm lesion would get a lumpectomy, sentinel node biopsy (let’s presume node negativity), radiation therapy and hormone therapy (if receptor positive). The other woman with the exact same disease, but with a mass close to the chest wall and non-palpable, comes back a year later and it may or may not be palpable then either. There is great variability in the degree of difficulty in clinical breast exams, size of breasts, consistency, etc. and a also the ability of the individual examiner. So two years later the lesion is now palpable, only now it’s 2.5 cm and there are also enlarged lymph nodes. This patient gets more extensive surgery, a complete axillary node dissection, and chemotherapy. And her long term survival stats are worse. I understand the great difficulty in evaluating the efficacy of screening programs but isn’t early detection, therefore easier more effective treatment, a primary goal. The second patient would be at quite a disadvantage because she was unlucky enough to have a lesion not easly found by clinical exam. Same disease, different management, and once diagnosed, different therapy morbidity and effectiveness. I understand the overdiagnosis problem, and it is a problem, but like you said, we don’t have the ability yet to know which tumors fall into that category.

  28. #28 jane
    February 17, 2014

    PA_in_VA – I think the next comment answered your question. Mammographically detected cancers may be less likely to receive mastectomy or full-blast chemo, but the high rate of overdiagnosis means that the total number of mastectomies still increases with screening. As Kurt implies, those who have small overdiagnosed cancers, or even DCIS, who choose lumpectomy over mastectomy are likely to be heavily pressured to accept radiation therapy and/or hormone drugs, both of which carry frequent life-altering side effects and will ultimately be fatal for a few.

    By some reasonable estimates, a third of screen-detected cancers are overdiagnosed (this study’s 22% excluded the count of DCIS). More than a few women who consider themselves high-risk would be willing to take unpleasant drugs if it would reduce their risk of a future diagnosis by one-third. As a woman without exceptional risk factors, I can reduce my risk of a future diagnosis by one-third just by not getting aggressive screening. I like that. Talk about cheap and easy prophylaxis.

  29. #29 Narad
    February 17, 2014

    As Kurt implies, those who have small overdiagnosed cancers, or even DCIS, who choose lumpectomy over mastectomy are likely to be heavily pressure to accept radiation therapy and/or hormone drugs

    I’m not seeing how you arrive at this characterization from the comment itself.

  30. #30 jane
    February 17, 2014

    Kurt takes it as a given that a woman with a small cancer who chooses breast-conserving surgery will also receive radiation and very possibly several years of hormone drugs. Since there is no way to know which small tumors are overdiagnosed and the goal of the oncologist is usually to reduce relative recurrence risk as much as possible even when the absolute risk is low, the many overdiagnosed women are very likely to receive either a mastectomy or radiation and perhaps more. I have been seeing on other websites comments of the “mammogram saved my life” type and more than one, I noticed, has described receiving both surgery and radiation following a DCIS diagnosis. A good portion of those seem to believe that DCIS is cancer.

  31. #31 Narad
    February 17, 2014

    Kurt takes it as a given that a woman with a small cancer who chooses breast-conserving surgery will also receive radiation and very possibly several years of hormone drugs. Since there is no way to know which small tumors are overdiagnosed and the goal of the oncologist is usually to reduce relative recurrence risk as much as possible even when the absolute risk is low, the many overdiagnosed women are very likely to receive either a mastectomy or radiation and perhaps more.

    The example cited IDC and therefore, by definition, was not a case of overdiagnosis.

  32. #32 Sandman2
    San Pedro
    February 18, 2014

    I certainly understand how misdiagnosis/overdiagnosis can cause harm. But what I am missing here is the rest of the percentage. If 22% are overediagnosed, then 78% are correctly diagnosed. Would that be correct to say? And if so, aren’t those odds pretty good compared to doing nothing and having a huge surprise years later?

  33. #33 Lola
    February 18, 2014

    The problem is that this study is being used in newspapers like il salvagente in Italy (a newspaper that “helps” consumers making the right choices) to convince women that mammography is completely useless, if not dangerous.

  34. #34 Nutrition prof
    February 18, 2014

    While a bit off topic-do you have an opinion about the results of the Women’s Health initiative arm on estrogen and breast cancer? I have a colleague who believes the reason for the reduction in breast cancer incidence since that arm if the trial was halted proves that estrogen is a a promoter of breast cancer, not an initiator. I find it hard to believe the drop in cancer could be related to estrogen therapy-could occur so quickly. Any thoughts?

  35. #35 Michael Finfer, MD
    February 18, 2014

    It is important to note that we are discussing the general population here. Patients known to be at high risk of developing breast cancer, such as BRCA mutation carriers, are not included in this discussion. For mutation carriers, enhanced breast cancer screening is usually recommended to begin at age 25-30 and to continue throughout life.

  36. #36 Herb Kressel
    Boston
    February 18, 2014

    Dr. Baines is very much a zealot and I personally reserve judgment on her latest study. The NCI and the American Cancer Society have independently reviewed all of the available data and consistently find a 20-30% reduction in breast cancer mortality due to mammography. That is the fact.
    I personally have lots of problems with the term “overdiagnosis,” because it is not over diagnosis. Pathologically these patients have cancer and it can’t be distinguished from the more aggressive forms by any mean possible. In fact if there is a problem it is “overtreatment,” but if we termed it that the surgeons, and internists would be on the hook for deciding who they shouldn’t treat. It would of course be an untenable position, so the alternative is “ostrich medicine” keep your head in the sand until it manifests as aggressive. So, by using the term “overdiagnosis” they say we shouldn’t find these because when the aggressive ones grow and when we find them they for the most part will respond to surgery and chemotherapy. That’s easy for them to say but not so easy for the patients who have to deal with a potentially worse prognosis and more aggressive therapy. There were a series of letters to the Editor in the New York Times by patients all of whom wanted no part in delayed diagnosis and the attendant need for chemotherapy and it’s complications.

    The issue of indolent cancer is present with many tumors. In colon cancer we routinely take out premalignant polyps over 5mm. Most of these are benign. In prostate cancer physician offer “surveillance” and “watchful waiting.” This is good for some but many find it very stressful not knowing if they will have a rapid growth and wind up with an advanced lesion. In my experience it is hard for people to stay on this path once their PSA ( used to follow tumor and BPH growth) starts to rise, even slightly. The answer in my view is not to stop breast cancer screening but rather to do more work on risk stratification to determine the likelihood of aggressive tumor behavior.

  37. #37 Daniel Corcos
    https://www.researchgate.net/profile/Daniel_Corcos2/?ev=hdr_xprf
    February 18, 2014

    @ Michael Finfer
    BRCA carriers represent 2 to 10 % of breast cancer patients, and there is no reason to think that they have been excluded from the study in the 80s. Of concern is the fact that the BRCA gene is involved in DNA repair, which makes X-ray mammography at risk.

  38. #38 jane
    February 18, 2014

    Narad – What is the basis for your claim that IDC is never overdiagnosed?

    Sandman2 – Almost all of those were correctly diagnosed as having cancer, yet (as the blog post explained) some would never have died of it, so they are overdiagnosed. The rate is probably more like one-third when you add in cases of DCIS, which many patients are led to believe is cancer. Yes, if you take it as a given that you as an individual have just been screen-diagnosed with cancer, the odds are that it is in your interest to treat it, even though the chance that early treatment will change your ultimate cause of death is relatively low. But on the population level, aggressive screening increases lifetime risk of diagnosis so much that the total number of mastectomies and/or radiation treatments increases. The chance that I will be harmed by overdiagnosis, if I pursue aggressive screening, substantially exceeds the chance that I will be helped by early diagnosis.

  39. #39 Michael Finfer, MD
    February 18, 2014

    Since the BRCA genes were not discovered until the ’90’s, of course some of those patients were included in the study, but that is not the issue I was trying to discuss. I merely wanted to point out that the guidelines we are discussing are only to be applied to women of “ordinary” risk.

    I’ll bet if the authors went back and removed patients subsequently found to harbor mutations from the data, the issue of over diagnosis and treatment would appear to be even worse than they are now reporting since those patients have a tendency to develop highly aggressive breast cancers.

  40. #40 Narad
    February 18, 2014

    Narad – What is the basis for your claim that IDC is never overdiagnosed?

    Let’s be clear that the case posited was not found by mammographic screening, so we’re talking about overdiagnosis due to physical examination. Anyway, yes, it was incorrect of me to suggest that IDC is never overdiagnosed, given that it’s an epidemiological notion in the first place.

    Nonethess, “those who … choose lumpectomy over mastectomy are likely to be heavily pressured” still strikes me as something you simply declared to be present in the original comment, which didn’t mention mastectomy at all and simply outlined the standard of care.

    Assume for a moment that it was identified by a core needle biopsy; would you recommend ignoring a 1 cm infiltrating malignancy of this type? How likely is it that mastectomy would even be recommended? For that matter, what are the odds that someone would be “heavily pressured” not to insist on a mastectomy?

  41. #41 jane
    February 18, 2014

    Narad – You acknowledge that Kurt’s assumption that a 1-cm cancer would be treated with radiation if the breast was not removed is consistent with the “standard of care.” He clearly expected that such cancers that weren’t palpable, but were found by mammography, would be similarly treated. Yet you seem to doubt that women who might initially be inclined to choose less treatment than the “standard of care” will be “encouraged” to change their minds. It is indeed true that many women who feel great fear of breast cancer voluntarily choose mastectomy and even double mastectomy in cases when it is quite unlikely to benefit them. However, a woman who says she wants lumpectomy without radiation – even, at some centers, for DCIS – is likely to be told, sternly and with various levels of death threat, that her preferences are unacceptable. That’s a minority experience, but if you pay attention to enough diverse women’s stories, it does exist.

    I doubt many people would “recommend ignoring” a 1-cm genuine malignancy – DCIS is another matter. However, the question of what it is rational for one individual who is stipulated to have a given diagnosis to do is totally unrelated to the question of what it is rational for a large group of healthy individuals to do in the pursuit of such a diagnosis. Mammography is starting to look like PCA screening for “early detection” of prostate cancer. Indeed, it does prevent a few deaths from prostate cancer – but the costs include a much larger number of unnecessary biopsies and overtreatments, which are often disabling and occasionally fatal, so an average man’s expected total of quality-adjusted life years is higher without screening. Yet if you propose an imaginary situation in which one individual has already been diagnosed, most will choose treatment (even if it has about a 2% chance of saving their lives).

    As with so many things, though, the negative math on mammography means nothing except filtered by individual values. If a particular woman had extreme fear of breast cancer and no fear of iatrogenic heart disease or lymphedema, she might think aggressive screening worthwhile even if by a pure count of QALYs it did more harm than good. I, by contrast, view iatrogenic harm – which you paid a lot of money to have inflicted on you – as harder to bear than comparable harm occurring naturally by mere bad luck, so if screening at a certain age is a net zero by objective measures, I judge it as negative.

  42. #42 Daniel Corcos
    France
    February 18, 2014

    @ Michael Finfer
    The issue of overdiagnosis is raised due to the fact that the two curves line up almost exactly. If BRCA1 and BRCA2 carriers were removed from the study, it could be found that non BRCA carriers may benefit from screening. In any case it would be important to know the proportion of breast cancers from BRCA carriers in the two arms of the study.
    https://www.researchgate.net/profile/Daniel_Corcos2/?ev=hdr_xprf

  43. #43 Narad
    February 18, 2014

    You acknowledge that Kurt’s assumption that a 1-cm cancer would be treated with radiation if the breast was not removed is consistent with the “standard of care.”

    Yes.

    He clearly expected that such cancers that weren’t palpable, but were found by mammography, would be similarly treated.

    Yes, and that they would progress until detected.

    Yet you seem to doubt that women who might initially be inclined to choose less treatment than the “standard of care” will be “encouraged” to change their minds.

    My point was that I doubt the suggestion that your desired narrative was actually contained in or intended by Kurt’s comment, but that would be for him to say.

    It is indeed true that many women who feel great fear of breast cancer voluntarily choose mastectomy and even double mastectomy in cases when it is quite unlikely to benefit them.

    Would you care to back this up?

    However, a woman who says she wants lumpectomy without radiation – even, at some centers, for DCIS – is likely to be told, sternly and with various levels of death threat, that her preferences are unacceptable.

    There is no reason to broaden this to include DCIS.

    That’s a minority experience, but if you pay attention to enough diverse women’s stories, it does exist.

    So “many” women opt for useless mastectomy without a word being uttered, but it’s “likely” that “death threats” will issue forth for refusing treatment aside from surgery, despite which likelihood, it’s a “minority experience”?

    I doubt many people would “recommend ignoring” a 1-cm genuine malignancy

    If one defines overdiagosis as disease that doesn’t need to be treated rather than a statistical excess compared with the absence of a screening modality, then, given this, I don’t know why you objected to my claiming that the example didn’t represent a case of overdiagnosis in the first place.

    DCIS is another matter.

    Indeed.

    However, the question of what it is rational for one individual who is stipulated to have a given diagnosis to do is totally unrelated to the question of what it is rational for a large group of healthy individuals to do in the pursuit of such a diagnosis.

    Do you think “in pursuit of” is a bit loaded here? Is it a silent changing of the subject of the clause?

    Mammography is starting to look like PCA screening for “early detection” of prostate cancer.

    For certain values of ‘similar’, which I suppose is implied by the scare quotes around “early detection.”

    Indeed, it does prevent a few deaths from prostate cancer

    “A few” seems to be something of an understatement.

    but the costs include a much larger number of unnecessary biopsies and overtreatments, which are often disabling and occasionally fatal

    This is obviously inherent to why anyone is discussing overdiagnosis to start with. I would nonetheless like to see some quantification of both often “disabling” and occasionally “fatal” with modern numbers and relevant comparisons. One finds here a 30-day mortality rate of 1 in 1000 after radical prostatectomy. This appears to be comparable to simple appendectomy (goo-dot-gl/jRqSKx; I’m out of links).

    so an average man’s expected total of quality-adjusted life years is higher without screening.

    If you go back to Heijnsdijk et al. (the first link), there does not appear to be sufficient evidence to make such a blanket statement.

    Yet if you propose an imaginary situation in which one individual has already been diagnosed, most will choose treatment (even if it has about a 2% chance of saving their lives).

    I am not proposing imaginary situations, much less making specific assertions regarding the imaginary psychodynamics of imaginary situations.

    As with so many things, though, the negative math on mammography means nothing except filtered by individual values.

    Does this statement “mean” anything?

    If a particular woman had extreme fear of breast cancer and no fear of iatrogenic heart disease or lymphedema, she might think aggressive screening worthwhile even if by a pure count of QALYs it did more harm than good.

    Sure, if she also had no ability to rationally assess the comparative risks, which I suppose is the payload of “extreme fear.”

    I, by contrast, view iatrogenic harm – which you paid a lot of money to have inflicted on you – as harder to bear than comparable harm occurring naturally by mere bad luck

    Could you be more specific about the nature of “mere” bad luck? Deciding not to do something is a decision all the same.

    so if screening at a certain age is a net zero by objective measures, I judge it as negative.

    If it’s actually this simple and rational, I don’t see why you feel the need to drag “death threats” and “in certain centers,” etc., into the equation. It’s no longer a matter of public policy, it’s simply your individual choice to skip screening based on your individual preference for the source of possible negative outcomes.

  44. #45 Michael Finfer, MD
    February 19, 2014

    It is generally agreed that mutation carriers benefit from screening. If you take them out of the data, you remove a subset of patients who benefit from screening, leaving everyone else. You also change the denominator. What may happen is that the percentage of patients who benefit from screening will drop. For example if 12/100 patients benefit, 12%, and you take out six of them, then the proportion of patients who benefit from screening is 6/94 or about 6.4%. The curves may separate in an unfavorable manner.

    Of course, we will not know if this is the case unless the authors reanalyze the data, but that is is my expectation.

    Since we are operating on statistics, you will end up with a few patients who might have benefitted from screening not getting it, but this is where regular breast examinations fit in, to catch those patients.

    Of course, there are several important factors pushing to maintain the old system, namely radiologists, advocacy groups, malpractice attorneys, and some surgeons and oncologists. As I said, it may be quite some time before we see change.

  45. #46 jane
    February 19, 2014

    Narad, obviously you have no respect for me personally and that’s fine, but there’s a lot of writing out there by medical researchers on the subject of overdiagnosis of both breast and prostate cancers. If you carefully read and accepted just what Orac has said about it, you would not have made some of the questionable statements in your last message. If you were keeping up with discussion on the subject, you would have seen professionals discussing the low likelihood of benefit of preemptive double mastectomy in non-BRCA carriers. And if you read what non-professional women have to say on the subject, you would be aware of the diversity of women’s preferences for treatment and the negative experiences and side effects some report. I make my decisions based on numbers, not artificially created fear. I don’t think there is anything more we can say to each other.

  46. #47 Daniel Corcos
    https://www.researchgate.net/profile/Daniel_Corcos2/?ev=hdr_xprf
    February 19, 2014

    @ Michael Finfer
    “It is generally agreed that mutation carriers benefit from screening.”
    No:
    http://www.ncbi.nlm.nih.gov/pubmed/22956590

  47. #48 mrs. eccentric
    February 19, 2014

    Thank you so much for this article, and for taking overtreatment seriously.

    I’ve had chronic very aggressive/chronic asthma since age 15, i’m now 51. I’ve had buckets and buckets of corticosteriods to keep me from dying, a very good tradeoff!!! However, i have extraordinarily debilitating nerve damage from this treatment and will have it until i die – i cannot work, the only meds that i can tolerate and that work are heavily monitored (and constipating, i eat a lot of graham crackers). I limp and am very glad when i get down to 3 on the 1-10 pain scale (once or twice a week, i’m generally more around 4-5). It’s very difficult for me to get the exercise i really should in order to help with the asthma and etc.

    Of course this impacts all mundane aspects of my life too. As just one instance I have not been able to bathe normally for about a decade now. Between the pain of a shower (yeah, water hitting the skin is painful), and the clumsiness/instability from the wacked out nerves making time in the tub or shower too iffy it’s too nerve wracking and uncomfortable. Meet the queen of the sponge bath and shampoo in the sink.

    Similar nerve damage is not uncommon with many of the cancer therapies. If it gives you five more years in which to see kids graduate college, grandbabies born or take the dream fly fishing trip to the Andes then hell yeah it’s worth it! If you’re in your fifties and looking at 20-30 years of a 30% life for No Reason At All – that is very very bad. Needless to say i’ve been around many health care people from the janitors on up, and none of them want to see anything like that happen. The huge majority of them just want to help people.

    Ironically yesterday i ended up in the ER with symptoms very similar to ones i had several years ago due to pulmonary embolisms***. Turned out no clots but i’m profoundly anaemic (undiagnosed,oh joy, more tests). I was very happy to hear that CAT scans these days can detect the most minute of clots (again starting a discussion on ‘what is truly in the patient’s benefit to treat?” as blood thinners have significant risks) but was still in the ‘doing something is better than doing nothing’ brain mode of most of us USA citizens. So i asked the good Dr. ‘why can’t we just treat for the clot and see if my XXX symptoms resolve?” and he replied. “Because it could kill you.”

    oh. in my defense, i’ve been feeling really bad and not mentally swift. Obviously the anaemia could be due to a bleed somewhere, and blood thinners are just like cranking that baby up to 11 – hullo bleeding to death internally, heart attack, stroke, you name it! I felt like a dolt, but that’s why you go to the pros when you feel that rotten. And i’m sure all you medical types, and many smart non-med cookies, saw that one coming a mile away :)

    I know this is long, but people really don’t get why overdiagnosis/treatment is not a neutral or just ‘well, some of us have an inconvenience so someone else can live’, it is actively bad. I notice many public medical educators downplay the nasty effects as well, i supposed because they don’t want people to avoid screening.

    But we need good information and honest discussion. Sure, the anxiety and waste of limited resources ain’t great. But you’re also very likely to get people who, in the prime of life, can no longer work, or exercise, or enjoy even the everyday fun stuff like a hot shower. And someone is i’m sure gonna die – my bonus mom knew a lady who died from an infection after toe surgery for peet’s sake. Of course it’s rare but if it’s you it’s 100% as they say.

    I think we’re smart enough and have enough resources to figure out a better balance. Someone with Angelina Jolie’s risk factors needs good info and smart people to talk to about what she can do. We need to figure out which tumors are just basically part of the ‘as we age, we get lumpy’ scenario so those people can go on to enjoy long and lumpy lives.

    Again, thank you so much – this topic is very complicated and doesn’t get hardly any sensible discussion anywhere. I wanted to give people a real feel for how over treatment can have very severe, long term consequences.

    A gold star goes to anyone who has read all the way to the end :) Happy Day!!!! steph

    ***clot resulted after a couple of PICC lines used for IV antibiotic treatment, yes it was the non-clot inducing kind, no i did not report it as i only had so much energy after almost croaking and could not find anywhere to do such and really you think it would be like an automatic thing for the pros to do to avoid clots from PICC lines, especially as so many are used in pregnant ladies?

  48. #49 Nina
    LA
    February 19, 2014

    I was diagnosed with DCIS in the fall of 2011 & underwent lumpectomy & then a margin clearing surgery & radiation. I refused to even consider drug therapy. Though my care at UCLA was excellent, now hearing that DCIS may not even be considered to be “cancer” & that my treatment may have been unnecessary, well, I’m not particularly happy looking down at my left breast. What’s done is done, but should I ever be told I have DCIS again, I’m gonna go for “watchful waiting” AND restricting the number of mammograms that I get. I’ve read up on the new BSE technique & will practice that a bit more faithfully.

    • #50 Orac
      February 19, 2014

      I really wouldn’t recommend that if the DCIS has factors indicative of high risk of progression to malignant disease, such as comedo necrosis, high grade, etc. Actually, I wouldn’t even consider recommending that for anything other than the tiniest, lowest grade DCIS. We just don’t know enough and can’t predict well enough.

  49. #51 Narad
    February 19, 2014

    Narad, obviously you have no respect for me personally and that’s fine

    I wouldn’t have spent the better part of an hour responding in detail I were trying to be dismissive.

    but there’s a lot of writing out there by medical researchers on the subject of overdiagnosis of both breast and prostate cancers.

    This was never in dispute.

    If you carefully read and accepted just what Orac has said about it

    What make you think that I haven’t?

    you would not have made some of the questionable statements in your last message.

    Such as pointing out that your statement about the QALY equation for prostate cancer doesn’t appear to be justified? If you’d like to be specific, I’m always willing to educate myself.

    If you were keeping up with discussion on the subject, you would have seen professionals discussing the low likelihood of benefit of preemptive double mastectomy in non-BRCA carriers.

    But so what’s the source of these contralateral prophylactic mastectomies? You acknowledge right here that it’s not a top-down phenomenon from oncology, viz., “death threats.”

    And if you read what non-professional women have to say on the subject, you would be aware of the diversity of women’s preferences for treatment and the negative experiences and side effects some report.

    This obvious fact was in no way necessary for my original point, which was simply that it appeared to me that you were pointing at one thing and claiming that it contained another of your own choosing.

    I make my decisions based on numbers, not artificially created fear.

    Once again: “I, by contrast, view iatrogenic harm – which you paid a lot of money to have inflicted on you – as harder to bear than comparable harm occurring naturally by mere bad luck, so if screening at a certain age is a net zero by objective measures, I judge it as negative.” The numbers are secondary in this statement, and “artificially created fear” is the lever arm.

    I don’t think there is anything more we can say to each other.

    Don’t blame it on me.

  50. #52 Michael Finfer, MD
    February 20, 2014

    I did not suggest that screening of mutation carriers is without risk. I said that it is generally agreed that it is effective. There is a difference.

  51. […] Can’t Get Their [sic] From Here: What Buzzfeed’s Questions Tell Us About Creationism The Canadian Breast Screening Study attacked: Why do doctors have such a hard time with the concept … Population Genetics Resources & Books I heart you Suspicious Virus Makes Rare Cross-Kingdom […]

  52. #54 Horace Boothroyd III
    February 20, 2014

    Here’s your key sentence”

    “whether this is “worth” it is more a value judgment than a scientific judgment, although that value judgment has to be informed by accurate science.”

    When we are lucky the science is so clear that the decision makes itself, but even in the more typical case of the evidence being equivocal it serves as a useful guide.

    My personal opinion is that evidence shows that people need to relax for a bit and not get so worked up. If the treatment either cures or kills, and after thirty years we still don’t have a clear answer, the truth could easily be that the effect is so small that we can stop worrying and allow the experts to sort it out it peace.

    For those who are about to ask, this is my opinion about prostate cancer screening as well – I am not simply poopooing the concerns of the ladies, safe in my estrogen deficiency.

  53. #55 Daniel Corcos
    France
    February 21, 2014

    @ Michael Finfer
    It is effective in inducing cancer, with this I would agree.
    @ Horace Boothroyd III
    From one side, we have a very reasonable assumption that early diagnosis could be beneficial, and from the other side, we have good evidence that X-ray irradiation causes harm to BRCA carriers. Isn’t it time to integrate these data?
    http://www.youtube.com/watch?v=FBLnL4XA6fc

  54. #56 Dangerous Bacon
    February 21, 2014

    Daniel Corcos: “@ Michael Finfer
    “It is generally agreed that mutation carriers benefit from screening.”
    No:
    http://www.ncbi.nlm.nih.gov/pubmed/22956590

    Daniel, did you notice that the paper you linked to does NOT assert that mutation carriers do not benefit from screening.?Quite the opposite, as it recommends use of MRI for screening in these patients.

  55. #57 Daniel Corcos
    France
    February 21, 2014

    @ Dangerous Bacon
    It’s clear that mutation carriers do not benefit from X-ray screening, as it increases their likelyhood to get breast cancer. Concerning MRI, it is clear that the recommendation is good, but there is no proof in this paper that early diagnosis is more beneficial in mutation carriers than in the general population. In any case, in analyzing the CNBSS results, one has to take into account this population of BRCA carriers that might have developped more cancers because of X-ray irradiation.

  56. #59 SusieQ
    Australia
    February 28, 2014

    With regards to DCIS – you cannot know how life threatening DCIS might be unless you excise it and test it – what if there is a micro invasion – you can’t see that unless you remove it and test it. I’ve seen women with DCIS got to Stage IV all due to that micro invasion.

    My own breast cancer was not palpable ILC small but very high grade and HER2+ve – boy am I lucky I had that screening mammo and it was found before it grew much bigger and spread to my lymph nodes.

  57. […] was a study published that cast more doubt on current mammography guidelines. It is not like the Canadian National Breast Screening Study whose results were published a couple of months ago in that it does not find that screening […]

  58. […] how Daniel Kopans attacks any study that finds mammography to be less effective than thought (or even ineffective) in decreasing deaths from breast cancer. There is, however, a form of backlash against criticism […]

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