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In which Dr. Gorski is taken to task by an eminent radiologist for his posts on mammography

40F MLO DMMG

Introduction: An unexpected e-mail arrives

One of the consequences of the growing traffic and prominence of this blog over the last few years is that people who would otherwise have probably ignored what I or my partners in blogging write now sometimes actually take notice. Nearly a decade ago, long before I joined this blog as a founding blogger, if I wrote a post criticizing something that a prominent academic said, it was highly unlikely that that person would even become aware of it, much less bother to respond to whatever my criticism was. I was, quite simply, beneath their notice, sometimes happily, sometimes unhappily.

It appears that those days might be over. Last week Dr. Daniel Kopans, a prominent Harvard radiologist and well-known long-time defender of screening mammography, sent me a rather unhappy e-mail complaining about my “attack” on him on this blog, a charge that he repeated in a subsequent e-mail. Before I publish his initial e-mail verbatim (with his permission), I would like to point out that, while it’s true that I did criticize some of Dr. Kopans’ statements rather harshly in my post about the Canadian National Breast Screening Study (CNBSS), even characterizing one statement as a “howler,” I would hardly characterize what I wrote as an “attack.” That to me tends to imply a personal attack. Using Dr. Kopans’ apparent definition, what he has said and written about investigators like those running the CNBSS, as documented in my post, about H. Gilbert Welch, who published a large study in 2012 estimating the extent of overdiagnosis due to mammography, and the U.S. Preventive Services Task Force (USPSTF), the group that in 2009 suggested changing guidelines for routine screening mammography in asymptomatic women to begin at age 50 instead of age 40, would appear to also qualify as “attacks.”

Be that as it may, I also wondered why Dr. Kopans hadn’t noticed my CNBSS post until more than three months after it had originally appeared. Then, the day after I received Dr. Kopans’ e-mail, my Google Alert on mammography popped up an article in the Wall Street Journal by Dr. Kopans entitled “Mammograms Save Lives: Criticism of breast-cancer screenings is more about rationing than rationality.” That’s when I guessed that someone probably had either posted or e-mailed Dr. Kopans a link to my previous post in response to that article. Given the confluence of events, I think it’s a perfect time to discuss both Dr. Kopans’ e-mail and his article, because they cover many of the same issues.

Before I go on, I feel obligated to repeat my mandatory disclaimer for posts about the controversy over screening mammography: What I am talking about is screening of asymptomatic women with mammography to detect breast cancer. If you have a lump or other breast symptoms, none of this discussion applies, and you should have your lump or other symptoms investigated by your doctor and undergo whatever imaging is deemed medically appropriate.

Dr. Kopans is displeased with Dr. Gorski

Here is the text of the e-mail from Dr. Kopans that arrived on Thursday:

Dear Dr. Gorski:

I was astonished and disappointed when I came across your “Posts” concerning breast cancer screening and your attacks on me. In particular the inflammatory statement that I was accusing the Canadian investigators in the Canadian National Breast Screening Study of “fraud”. I have never stated this and it was inappropriate for you to suggest it. There is no evidence of fraud in the CNBSS trial, but there is clear evidence that the fundamental requirements of a randomized, controlled trial were violated. I do not make up the rules for these trials. You are well aware that blind allocation is critical. When there is a statistically significant excess of advanced cancers allocated to the screening arm and the coordinators had knowledge of the clinical examination findings and they allocated the women on open lists, and there was an excess of cancer deaths among the screened women you have to completely suspend scientific thought to not be concerned that there was a problem.

On top of that when there is not a single expert who does not agree that the mammography was poor to unacceptable and the size of the cancers was the same for the mammography group and the non-mammography group why would you even consider this a test of mammography screening? If you were involved in a trial and you felt that you had done a good job, you would defend your work against all criticism. I am unaware of any radiologist or technologist in the CNBSS who has defended the trial. I assume you do breast surgery. Dr. Miller has insisted that the nurses doing the clinical breast examination detected most of the cancers in the mammography arm. How often can you feel the cancers detected by mammography even when you know where to feel? How often do radiologists have to guide you to the lesion?

How can you defend a trial that has major implications and fundamental compromises by saying that we will simply get rid of the prevalence cases? Since it was not blinded, we have no idea how the allocation was compromised. Furthermore, Dr. Miller has acknowledged that as many as 25% of the control women had “diagnostic’ mammograms so they were not really contaminating the control arm. As I am sure you know, diagnostic mammography starts off with a bilateral screening mammogram so this is simply not true. The trial started with insufficient power (I am certain as an expert who is publically critical of a critic, that you have read all of the papers on the CNBSS ??)

Dr. Miller went public in the 1990′s claiming that mammography was squeezing cells into the blood leading to earlier deaths in the mammography arm. After causing major concerns, he withdrew the claim invoking ataxia telangiectasia, but now says it was because removing the primary allowed the metastatic lesions to grow faster. Even in mice where this happens it is a short lived phenomenon and the mice do not die any sooner – a point that Prof. Miller neglects to make.

If all of the problems with the CNBSS had occurred in a surgery or chemotherapy RCT you would be outraged that the results made it through peer review. You seem to have no problem defending a corrupted (in scientific jargon) trial when it comes to mammography screening. I have little doubt that your ego will not allow you to recognize your hypocrisy.

By the way – I am attaching my critique of the Bleyer and Welch paper. Dr. Bleyer has admitted in his rebuttal that they used “best guesses”. He also admitted that since they had no data on mammography, they could not fault mammography – yet they did. He is critical of my use of the data from the Connecticut tumor registry, yet the papers that I can find that looked at breast cancer incidence prior to SEER all used the Connecticut tumor registry. If you use the Connecticut data there is no overdiagnosis of invasive cancers (there were actually fewer than expected)

DCIS is a major unresolved issue, but this is well known. The Bleyer and Welch paper would have never been published had they only raised concerns about DCIS so they combined it with small invasive cancers just the way all experts combine the two – not actually.

I assume that since you defend the Bleyer and Welch paper you have seen a number of invasive cancers disappear on their own. Certainly with 70,000 each year you must have seen many such disappearing cancers.

If you are so concerned about overtreatment (over [sic] course overdiagnosis is the pathologists’ failing) why are you (oncologists) poisoning so many women who do not need it? Among women diagnosed with breast cancer (all palpable) in the 1940′s treated only by mastectomy 30% were alive 30 years later, yet all would be treated with systemic therapy today. Why are you overtreating all these women?

There are numerous legitimate concerns about breast cancer and breast cancer screening, but it is not reasonable to withdraw support for a test that has been shown with greater certainty than any other screening test to save lives, by supporting flawed “science” and misleading physicians and the public.

Daniel B. Kopans, M.D.
Professor of Radiology, Harvard Medical School
Senior Radiologist, Breast Imaging Division
Department of Radiology, Massachusetts General Hospital
Avon Comprehensive Breast Evaluation Center

I must admit that I was disappointed in this response.

Dr. Gorski responds to Dr. Kopans, with trepidation

It’s always a bit of a wake-up call to be so castigated by such a prominent radiologist. Did I err? What makes me think I have what it takes to get into a serious discussion with the likes of Dr. Kopans? After all, what’s a relatively unknown surgeon and translational researcher compared to such an eminent radiologist as Dr. Kopans? Still, one of the greatest things about the Internet (and simultaneously the one of the worst things, as I have acknowledged), is that it lets anyone with an Internet connection voice his opinion. So here goes.

First, however, let me point out that there is actually some common ground between Dr. Kopans and me, in the hopes that he will understand that I am not his enemy, merely a critic of certain statements of his. There is a difference. Also, contrary to how I am sometimes portrayed (and what Dr. Kopans seems to be implying), I am most definitely not in the camp that believes that mammography screening programs should be abandoned, as has been proposed by various researchers and pundits, and I do believe that mammography saves lives. I’m even the team captain for our cancer center’s team in the local Komen Race for the Cure! Where I differ with Dr. Kopans is that I also accept the emerging evidence that overdiagnosis due to mammographic screening is a significant problem that leads to overtreatment. In other words, in some women mammography can cause harm, and more harm than Dr. Kopans would apparently acknowledge, and I believe that our current guidelines should be changed to reflect that emerging science and find the “sweet spot,” where benefits are maximized and harms minimized. Having looked into this for nearly five years now, I understand the acute discomfort of change that comes from questioning a medical intervention that I once accepted and finding that I agree that the guidelines do need to be changed.

Next, let me deal with what I view to be the most heartening revelation, namely that Dr. Kopans denies accusing the CNBSS investigators of research misconduct. This is a good thing, because such charges should never be made lightly. It is odd to me, however, how clearly puzzled Dr. Kopans appears to be that a reasonable person might have honestly interpreted his rather over-the-top characterization of the CNBSS randomization process that way, which makes me feel reluctantly obligated to explain again how that could have happened and requires that I quote some of Dr. Kopans’ own words again:

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”.

He also went on to accuse the investigators of the CNBSS of intentionally ignoring an issue that would allegedly allow those doing the randomization to subvert the randomization. One notes that the American College of Radiology (ACR) response to the publication of the CNBSS uses very similar language, leading me to believe that Dr. Kopans had a major hand in writing it. If you don’t believe me, compare Dr. Kopans’ criticism of the study in the BMJ that I quoted in my original post and the ACR press release criticizing the study. The wording of the relevant sections about subversion of randomization is almost identical.

Given its virtually-identical charges against the investigators of the CNBSS, I find Dr. Jen Gunter’s discussion of the charges quite informative. She read the ACR press release and found its arguments…wanting. She even entitled her post Did the American College of Radiology accuse the BMJ mammography authors of misconduct? In her post, she looked at it a different way than I did when I wrote about the CNBSS, a way that to me is simultaneously simpler but probably more revealing than how I did it, by pointing out that the CNBSS authors stated in their paper that their randomization was blinded (true, as I pointed out). She then put it in context:

So the authors are saying their randomization was blinded and the ACR’s counter-claim is that is couldn’t have been. Both can’t be right. The ACR is either accusing the author of lying or saying he had rogue study nurses who didn’t follow protocol. The ACR does not provide any references to support this claim.

This last part of the ACR claim sounds a lot like school yard taunt, “You lied. How do I know? Because I said so.” It is the kind of claim one makes when one A) hasn’t thought it all through and is letting emotions rule, B) has an otherwise weak argument that needs to be bolstered, or C) you want to be over the top to get page clicks. This accusation actually leads me to evaluate the ACR’s other two claims with greater scrutiny.

One notes that an accusation that is in essence an accusation that the investigators lied in their scientific papers about the randomization process of their study or accusation that (1) they had rogue nurses who ignored study protocol in order to subvert randomization and (2) that they ignored evidence that their nurses were subverting randomization in that way is an accusation of fraud in my book. I further note that Dr. Gunter wrote both the Canadian and American Colleges of Radiology for evidence to support this accusation and got none. True, the ACR did respond, but provided no evidence. As I pointed out in my original article, I believe the authors did this adequately in both their paper reporting the results of the CNBSS and another article in which they answered charges like those leveled by Dr. Kopans and the ACR, and other reviews of the CNBSS failed to find convincing evidence for subversion. In any case, the vitriol in the debate over mammographic screening, particularly of women in their 40s, is nothing new.

While I do believe that Dr. Kopans does not think he was accusing the CNBSS investigators of research misconduct/fraud when he made those criticisms of the CNBSS randomization process, I can’t help but also note that back in the 1990s he did explicitly accuse other investigators of “manipulat[ing] data in a fashion that borders on scientific fraud” in their article in JAMA. He even sent letters with this accusation to George Lundberg, then editor of JAMA, and Haile Debas, then dean of the UCSF medical school. Around the same time he characterized a recommendation by an NCI panel not to recommend screening for women in their 40s as “fraudulent” and “meant to mislead.” Even Laszlo Tabar, for instance, a radiologist who directs the Swedish Two County Trial of mammography, and a strong defender of mammographic screening programs whom I quoted in my post about the CNBSS, admitted in 1997 in the same article in Science that Dr. Kopans can be overly belligerent.

In any case, I suspect that Dr. Kopans is so convinced that mammography is such an unalloyed good that he does not react well to criticism of it and that Dr. Kopans and the ACR, honestly believing the CNBSS to be flawed beyond any redemption, wanted to show just that, to the point that they let their rhetoric get away from them. The bottom line is that at least two reasonable people (Dr. Gunter and myself), both of whom work in medical fields in which we have every reason to support mammography, were left with the impression that Dr. Kopans’ and the ACR’s criticisms of the CNBSS report in the BMJ were accusations of research misconduct. If there are two of us who interpreted it that way and were willing to blog about it, I’d be willing to bet that there were a lot more of us out there who interpreted his words that way. One hopes that Dr. Kopans will rein in his overheated rhetoric in future discussions and not be surprised how, given his history, his words are interpreted.

But what about the rest?

A lot of it is what has become fairly standard anti-CNBSS boilerplate that’s been repeated before over and over again, such as the claim that the mammography was substandard. This issue has been addressed before, as I discussed. As for the issue of Dr. Miller (the principal investigator of the CNBSS), even if true it’s irrelevant to whether the CNBSS results were valid or not; so I call non sequitur on that one. As for Dr. Kopans’ accusation that I am a hypocrite and such an egotist that I will never admit that I’m wrong, now—as Crocodile Dundee once said about a knifethat’s a personal attack. (True, it’s in an e-mail, but Dr. Kopans gave me permission to post it; so it’s not as though he’d be likely to shy away from saying it in public.) It’s unlike any criticism I wrote in my original post and anything that I’ve written in this post. He’s also wrong. If I saw a surgical study with flaws correctly judged as massive as the flaws portrayed in the CNBSS by Dr. Kopans, I quite likely would comment. It’s just that I don’t agree with Dr. Kopans’s characterization of the magnitude of the flaws of the CNBSS. In any case, I leave the reader to make his or her own judgment reading my original post, Dr. Kopans’ response, and this post, particularly in light of his denigration of my qualifications with respect to his, as I move on to other substantive points.

The Bleyer and Welch paper, as regular readers might remember, was published in the New England Journal of Medicine about a year and a half ago. I discussed it in detail when it first came out. One notes that my assessment was not quite as effusive as Dr. Kopans portrays it. I thought its findings were in line with the emerging body of evidence suggesting that overdiagnosis of breast cancer is more common than previously suspected. A key prediction of the hypothesis that detecting breast cancer earlier will lead to fewer deaths from breast cancer is that a screening test that leads to the detection of more early-stage cancers—and, yes, it is, contrary to Dr. Kopan’s assertion, reasonable to include ductal carcinoma in situ (DCIS) among early-stage breast cancers if one believes that a significant number of DCIS lesions will progress to invasive cancer—should lead to a decrease in the number of late-stage cancers. Bleyer and Welch didn’t find that. They found a large increase in the incidence of early-stage cancers but a much smaller decrease in the incidence of late-stage cancers. That’s it.

It’s not as simple as Dr. Kopans makes it out to be

What I’ve found since I first took a more intense interest in this topic is that many of the criticisms of such studies boil down to not believing that overdiagnosis is a real phenomenon in breast cancer. Yet, as I’ve explained before, translating earlier detection of breast cancer—or any cancer, for that matter—into better survival is far more complicated than most people, even physicians, think. Besides overdiagnosis, there are the complicating factors of lead-time bias (explained by yours truly here, here, and here) and length bias, in which the tumors detected by screening tests tend to be the more indolent and less deadly (explained by yours truly here and here). In the past, I have pointed out that the prevalence will increase for virtually any disease that is intensely screened for, using autism as my main example, as well as hypercholesterolemia and hypertension, and comparing it to the prevalence of DCIS, the latter of which has increased by 32-fold since the 1970s. Given that autopsy series routinely show that large percentages of people who die of other causes have foci of cancers such as prostate, breast, and thyroid cancer that never become clinically evident, why is it a surprise that mammography might lead to at least some degree of overdiagnosis?

Finally, I can’t help but note that a couple of observations Dr. Kopans makes are just silly, disappointingly so. (No, that’s not a personal “attack,” simply a characterization of my opinion of what he wrote. If Dr. Kopans can call me a hypocritical egotist, then the least concession he can give me is to let me refer to something he writes as “silly.”) First, there’s the part about how I must have seen so many tumors disappear on their own. I’m sorry, but there’s no polite way to say it: That statement is based on a complete misunderstanding of the concept of overdiagnosis. Those studies only include screen-detected tumors, but more importantly the current standard of care would be to treat all such tumors detected, meaning that every woman I see who has a screen-detected breast cancer will receive some combination of surgery, radiation therapy, chemotherapy, and/or hormonal therapy. I do not simply watch women with invasive breast cancer to see how many of them might regress. Because it would be completely unethical to propose doing so in a randomized clinical trial because of the lack of clinical equipoise in such a design, overdiagnosis must be inferred from population-level data, and it has been. Moreover, it’s important to note that it is currently not possible to identify which woman has been overdiagnosed at the time of diagnosis. I wish it were, because then we could obviate the major harm in mammography screening, and virtually eliminate overdiagnosis. Figuring out strategies to do so for DCIS has been a recent interest of mine as well.

Let’s go back to something that Dr. Kopans also wrote:

If you are so concerned about overtreatment (over course overdiagnosis is the pathologists’ failing) why are you (oncologists) poisoning so many women who do not need it? Among women diagnosed with breast cancer (all palpable) in the 1940′s treated only by mastectomy 30% were alive 30 years later, yet all would be treated with systemic therapy today. Why are you overtreating all these women?

In fact, I have discussed many times how it is important to provide women with the absolute benefits due to chemotherapy as well as the relative benefits. I like to use the example of a woman with a stage I cancer. I tend to round the numbers a bit for simplicity’s sake, but they’re close enough to make the point to a lay audience (and medical students, for that matter, when I’m teaching). So I tend to give an example of a woman with a stage I cancer who has a 90% ten-year survival with local therapy alone. If chemotherapy produces a 30% relative survival benefit (roughly correct, perhaps slightly too high), that would translate only to a 3% absolute survival benefit. In other words, 90 out of 100 women would have survived anyway but got treated, in retrospect “unnecessarily,” while seven women out of 100 would have died regardless but got treated, in retrospect “unnecessarily.” Only three out of a hundred who would have died were saved by chemotherapy. In other words, the number needed to treat (NNT) to save one life is 33. This is the main reason why a hot area of research is predictive testing, to identify who will and won’t benefit from adjuvant chemotherapy, and why we in the field view the OncoType DX test, as imperfect as its predictive power is, as a major advance that has saved thousands of women with early stage estrogen-responsive cancers from chemotherapy who wouldn’t benefit from it.

Of course, it should be noted that the higher the stage, the higher the risk of relapse and death, and thus the larger the absolute benefit of adjuvant chemotherapy. That’s why I’ve done a number of posts in which I take hypothetical cases and run them through Adjuvant!Online to illustrate my points. But I sure don’t sugarcoat problems with adjuvant chemotherapy, contrary to Dr. Kopans’ question. In any case, I’ve pointed out that chemotherapy has contributed to a major improvement in survival of breast cancer patients, even while lamenting how frustratingly…incremental…improvements in chemotherapy drugs have been. I obviously don’t expect Dr. Kopans to have read all my old stuff (that would be ridiculous), but he does seem rather eager to leap to conclusions about me.

It might be instructive to compare the NNT for chemotherapy, which at its worst in stage I breast cancer, is around 33 to 50, to the number needed to screen (NNS) to save one life for mammography. For instance, Esserman et al. estimate that to avert one death from breast cancer with mammographic screening for women between the ages of 50-70, an age range intentionally chosen because it is the age range for which mammographic screening is the least controversial, 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.”

It’s also been noted that the younger the patient group, the higher the NNI (number needed to invite to screening) is, ranging from 377 for women aged 60-69, resulting in an absolute risk reduction of dying from breast cancer in the next ten years of approximately 0.3%, to 1,904 for women aged 40-49, translating to an absolute risk reduction of 0.05%. Of course, mammography is not chemotherapy, but I could still turn Dr. Kopans’ argument around and ask him, why we are screening all these women who do not need it, all to produce an absolute reduction in the risk of dying from breast cancer that is so small? (I realize that chemotherapy is “poison” and mammograms are not, but it is still not an unreasonable point.) I would point out that it’s a value judgment to say how small a survival benefit is too small, but there must be a cut-off. If there were not, there’s no reason not to start screening women as soon as they hit age 21, but not even Dr. Kopans proposes doing that, as, below a certain age, the benefit becomes either too small or nonexistent. The risk of breast cancer with age is a smoothly increasing curve; there is no sharp cutoff. Where we choose the cutoff to begin screening, age 40 or age 50, is a value judgment based on an assessment of the risk-benefit ratio and, yes, to some extent cost. That’s reality. I happen to believe that it’s likely worth it for women over age 50; I’m no longer so sure it is for women under age 50, hence my endorsement of a recommendation for personalized screening below age 50, a concept that is anathema to Dr. Kopans. Either way, his choice of age 40 as the time to start screening is no less arbitrary a cut-off than is age 50, and the observation that cancer mortality in Europe is not higher than it is in the US reassures me that I’m at least not entirely mistaken in my conclusions.

In his e-mails and his WSJ article, Dr. Kopans portrays any questioning of the value of mammography as “a disconcerting effort afoot to reduce a woman’s access to mammography screening for breast cancer by making it seem useless or even harmful,” or similar language in which he ascribes dire motives to those with whom he disagrees. To Dr. Kopans, it seems, there can’t be an honest scientific and medical disagreement that leads some researchers and clinicians to question the “one size fits all” design of the current mammographic screening guidelines. Oh, no. It has to be rationing, and that’s how he portrays it in his WSJ article. When Bleyer and Welch estimate a large amount of overdiagnosis from screening mammography, it can’t be because they go where the science leads them or have a legitimate academic disagreement with Dr. Kopans. Oh, no. It has to be yet another effort to “reduce access to lifesaving screening tests.” Dr. Kopans dismisses as a “new effort to limit access to screening” the reasonable suggestion, based on analysis that screening produces more overdiagnosis the less prevalent a disease is in a population screened (which is the reason why even Dr. Kopans doesn’t propose screening women below the age of 40—breast cancer incidence is too low) that developing risk-based screening could improve the efficacy of mammographic screening programs, reducing overdiagnosis and therefore overtreatment. He even concludes his op-ed, “It would be unfortunate to deny women access to screening based on flawed analyses or rationing in the guise of altruism.”

Disappointingly, that is a profoundly insulting characterization of researchers on the other side of a scientific disagreement, one that is beneath a professor of radiology as eminent as Dr. Kopans.

Those of us who take care of women with breast cancer all want what’s best for them. I accept that Dr. Kopans, pit bull that he is defending mammography against all attacks, does so out of a desire to help women to avoid dying from breast cancer. I just wish he’d grant his critics the same consideration. It’s understandable that he’s upset that I would have the temerity to criticize his statements. He should think of it as a dose of his own medicine—and a comparatively mild dose at that.

Posted in: Cancer, Clinical Trials, Public Health

Leave a Comment (76) ↓

76 thoughts on “In which Dr. Gorski is taken to task by an eminent radiologist for his posts on mammography

  1. goodnightirene says:

    Well, that post easily outlasted my huge morning coffee!

    That reminds me that I am due for a mammogram. Since I had them starting at age 40, can I skip some now? :-)

    1. David Gorski says:

      Sorry, but no.

      As for the length of the post, about 900 words of it come from Dr. Kopans, making it not that much more longer than average for me, at least my part, and I did divide it into three parts. :-)

  2. Jen Phillips says:

    Very graciously handled, Doc. Thanks for doing what you do.

  3. David Gorski says:

    Actually, there’s so much more, specifically a second e-mail that I didn’t have space or time to handle and two articles, a critique of the Bleyer & Welch paper by Dr. Kopans that he sent me, along with Archie Bleyer’s response. (This post had already grown long even by my standards, to the point where I fear a lot of people might not read the whole thing.) That doesn’t even count the likely unhappy additional response from Dr. Kopans when he gets around to reading this.

    I fear that there might have to be a part 2 of this post at some point in June. Or I could let things hash out in the comments for a while until I determine whether a part 2 is necessary. I should, however, point out to newbies here that a person’s first comment always goes to moderation. I will ultimately approve almost anything (remember certain commenters who like to call us names?), but if it’s not posted during my waking hours EDT, it might be several hours before I release the comment from purgatory. Even I have to get some sleep, you know. :-)

  4. Kelly Weatherly says:

    Dr. Kopans seemed a bit rude in his email and I think your response was very well presented. I have been following this blog and the other for a few months now and have really enjoyed the different perspectives. I have just turned 41 and already my doctor has been pushing mammograms because they are recommended at this age and not because I am high risk for breast cancer. After reading the post about the potential overdiagnosis and treatments of certain findings due to the mammograms I feel more confident in my opinion that I don’t need them as a routine screening at this time in my life. Thank you for taking the time to write these interesting and informative posts.
    Sincerely,
    Kelly Weatherly

    1. Sawyer says:

      I’m starting to wonder how many doctors are well aware of the risks associated with overdiagnosis but are trying to keep the discussion of mammograms as simple as possible for the sake of consistency. Telling women that there’s a single age cutoff and frequency that they should begin mammograms is going to be much easier than implementing some sort of ramp-up regiment. Are there other screening programs where healthcare professionals stick to an overly simplified program in lieu of one that is supported by the best evidence?

      Of course even if doctors want to employ simple recommendations for most of their patients, they should still be prepared to delve into the issue of overdiagnosis when it comes up in discussion. Like Kelly, my mother told me her doctors refused to even acknowledge this was a topic worthy of attention at her last check up. “Mammograms save lives” is a fine starting point, but when your patients start asking REALLY easy questions you better know how to answer them. Thanks to Dr. Gorski it took me 2 minutes to explain lead-time bias to my mother. If her doctors don’t understand it they aren’t getting the right CME.

  5. Vicki says:

    Argh! Tomorrow I will have the dreaded “Should I have my mammogram or now?” discussion with female asymptomatic 40-50 yo patients (lowly FP that I am) and will be (as usual) looked at suspiciously by the patient who assumes if I say, “Well, the evidence mammograms at your age is not that simple, and it might be okay to skip it” that I am an idiot and that they will be dead by July of advanced breast cancer. All of these patients of course have had the letter from “Insert Name of Big Local Hospital System” about how important mammograms are after you’re 40. Who am I to argue with “Insert Name of Big Local Hospital System”? Thanks, as usual, Dr. G for tidying up this giant plate of research data spaghetti in my head a bit (again) so comprehensively and graciously.

    1. Tazia Stagg says:

      Do you ever wish that you had the option of referring patients to a preventive medicine specialist for such discussions?

  6. Frederick says:

    Interesting post, But A long one :-) I have not finish it yet, I have to go to work now, Will continue reading on my phone during diner break :-), I did skip most of Kopans writing, He is not as interesting as you to read, it is you specialty after all.

  7. S Endecott says:

    a most enjoyable and educational read it has been; however, it required 3 – 6 oz cups of coffee to complete. I look forward to part II or any subsequent rebuttals Dr. Kopans may submit.

  8. Cornelia Baines says:

    As co-principal investigator of the Canadian National Breast Screening Study, I am surprised at Dr. Kopans’ claim he never has accused us of fraud in the conduct of study. Why then did he harass the Faculty of Medicine at the University of Toronto to conduct a forensic audit of our study? Why does he end his recent letter to the BMJ claiming the study was “corrupted”? Corrupt is corrupt. Why does he wrongfully insist we did not respect the randomization process when data so clearly indicate the contrary? As for his decades long assertion that our mammography was “poor”, how then can one explain the fact that our Screen 1 cancer detection rate was higher than in the Swedish Two-County study? It is always useful to go back to primary sources to resolve uncertainty and to look for likely conflict of interest in those who condemn the study.

    1. WilliamLawrenceUtridge says:

      It is always a delight when an expert takes time from their day to comment. Thanks and welcome.

    2. David Gorski says:

      One also notes that Dr. Kopans repeatedly referred to the trial as “corrupted” or “corrupted beyond use” in his response to this editorial:

      http://www.medscape.com/viewarticle/734977

      Personally, I think Dr. Vickers pretty much nailed it.

  9. Stella B. says:

    Vicki, do your best to explain and then let them decide. When you are my age you can look them in the eye and say, “I got my first mammogram at 50”. I recently suggested to my 78 year old mom that she could stop. She’s thinking about it.

    It sounds like Dr. Kopans has allowed his political views and financial interests to influence his scientific judgement.

    1. WilliamLawrenceUtridge says:

      I don’t know him or his finances but I take him at his word that it is the health of his patients (and, it should be said, his status as a radiologist) that prompts his concerns. He is a professor, isn’t he? So a salary i would expect.

      Could be wrong, of course.

      1. Windriven says:

        “Could be wrong, of course.”

        His choice of the WSJ as the venue for his editorial speaks volumes about his motives. The opinion pages are Petri dish to every form of laissez-faire capitalist and John Birch Society wing-nut political view imaginable. Karl Rove, for one, is a regular contributor.

        WSJ editorial pages have been home to scurrilous attacks on many health care reforms that might blunt the edge of unsustainable and indefensible levels of health care spending in the US. It would be easy to caricature the prevailing opinion there as immortality amid unbounded riches if only the godless liberals would go the way of triceratops.

  10. lilady says:

    Thank you Dr. Gorski, for another excellent post about screening mammograms and the USPHS Guidelines (which are not, BTW, set in stone).

    Now that I am logged in as subscriber to the WSJ, I have free access to Dr. Kopan’s article and I found it to be quite provocative, with his inferences of research fraud on the part of the Canadian Study researchers and the USPHS researchers.

    I’ve read each of the 88 comments posted on Dr. Kopan’s WSJ article; many of those comments have pointedly taken Dr. Kopan’s to task for his inflammatory and misleading article. Other commenters are downright disingenuous; with their reference to “death panels” and accusatory not-based-in science remarks about researchers who participated in the Canadian Study and the USPHS Guidelines. Unfortunately, Dr. Kopan’s has chosen to not reply, to those derogatory remarks.

    Thank you again, for your extraordinarily detailed posts about breast cancer and your willingness to take on quack cancer treatment practitioners…somethings that are sorely missing from Dr. Kopan’s articles.

    1. Sawyer says:

      Other commenters are downright disingenuous; with their reference to “death panels” and accusatory not-based-in science remarks about researchers who participated in the Canadian Study and the USPHS Guidelines. Unfortunately, Dr. Kopan’s has chosen to not reply, to those derogatory remarks.

      I don’t know whether to blame Dr. Kopan for not responding, but I do think it’s fair to assume than anyone publishing on WSJ op-ed page knows exactly what they are getting into. Point to all the good science coverage you want in the news section, you can’t ignore the fact the op-ed page has catered to paranoid anti-science nuts for over a decade. I’m surprised there’s no accusations of climate scientists sneaking into Canadian hospitals and doctoring the cancer screening data.

      I’m curious if Kopan tried to submit his critique to other newspapers before the WSJ.

  11. Etatro says:

    “I am certain as an expert who is publically critical of a critic, that you have read all of the papers on the CNBSS ??” I hate when people frame a question this way. It’s a use of facetiousness and hyperbole combined with arrogance that makes you wonder how these “eminent” personalities function in the real world. This, along with several other statements in his letter, make me think that he operates with a crippling (dangerous) level of hubris.

  12. R.w.Foster says:

    Genuine seeking of knowledge here: Is a mammogram anything like an ultrasound (other than the breast squeezing)? If no, what are the flaws with using ultrasound for detecting cancer, or lumps? If yes, then why are the ladies’ breasts sqeezed?

    1. Andrey Pavlov says:

      @R.W. Foster:

      If you want a much more detailed response, there are others more qualified than I, but the short version is as follows.

      A mammogram uses x-rays and thus is a completely different modality to ultrasound. The key differences regarding mammography is that xrays can detect calcifications and has more resolution for detecting spiculation (spikiness) which are both more indicative of cancer (amongst other differences).

      In terms of detection of lumps – US is not a good modality for that. It is highly operator dependent (meaning that the technician’s skill and thoroughness are important) and thus parts of breast tissue can be missed or can be read differently depending on how the tissue is handled. The compression used in mammography is to create as even and flat a plane as possible so that the distribution of tissue can be uniform and thus prevent the xray from looking like there is something there when it is just an uneven amount of tissue it must penetrate through.

      US is (much) better than xray for determining whether a lump is solid or fluid filled. This is useful since being fluid filled is highly indicative of a cyst rather than a tumor.

      There are other differences, of course, but those are the broad brush strokes. In sum, mammography is superior for detecting a lump and US is useful for both further characterizing it and as a means by which to guide a needle biopsy as indicated.

      1. JJ says:

        We recently had the short version of the above conversation with my mum & older sister:

        Ultrasound is most useful once you know where to look. Mammography is most useful for finding the places to look.

      2. R.w.Foster says:

        Ah. Thank you. I always wondered about that, but didn’t dare ask someone in person. I didn’t want to come across as a creeper, or anything like that.

      3. lilady says:

        Last year, I had a mammography; I’m (much) older than fifty. After the mammography was read by a breast radiologist, I was advised that a “new dense nodule” was found on my left breast. The following day I returned to the radiology practice for a left breast 3-D mammography and left breast sonogram.

        Andrew Pavlov described the pressing of the entire breast between two plates to flatten the breast tissue and a woman then undergoes another “pressing” to get another view of the breast tissue, between the sternum and the axilla. The lab technician did a very thorough sonogram. I was very fortunate to have an immediate reading by the breast radiologist who confirmed that the “new dense nodule” was, in fact, a cyst.

        I experience considerable pain during mammograms…greatly lessened if I have 5 mg. Vicodan on board, taken one hour before my scheduled appointments.

  13. WilliamLawrenceUtridge says:

    Anyone else look at the image and say ‘is that an xray of a scrotum?’

    No?

    Nobody?

    Ok, never mind.

    1. brewandferment says:

      that didn’t come to mind, but it did look pretty strange.

      one of my siblings was a radiology scutworker as a teenager and brought home an X-ray of a broken chicken bone wrapped to exactly resemble a penis…

    2. n brownlee says:

      I really can’t remember, WLU… it’s been so long…

    3. Windriven says:

      I thought it was a screen shot from the Southpark episode where Randy Marsh was bouncing around on his distended scrotum.

  14. Ladyatheist says:

    Mammograms are PAINFUL! Let’s drop them altogether and do ultrasounds or CT scans mkay?

    1. David Gorski says:

      Here’s the problem. Ultrasound is not good for screening. It’s only good for evaluation of detected abnormalities, either lumps on physical exam or abnormalities on mammography. CT uses way too much radiation to be useful for a yearly or every-other-year screening test, and it’s not very good for detecting breast cancer anyway. They can’t replace mammography, at least not now.

    2. Harriet Hall says:

      Mammograms are not painful for everybody. The worst I have ever experienced is mild discomfort, only for a minute or so. And even when they are painful, they’re nowhere near as painful as dying from breast cancer.

  15. Ladyatheist says:

    Okay, but it would be nice to see at least one discussion of the issues acknowledge the pain.

  16. MadisonMD says:

    Dr. Kopans says:

    If you are so concerned about overtreatment (over [sic] course overdiagnosis is the pathologists’ failing) why are you (oncologists) poisoning so many women who do not need it? Among women diagnosed with breast cancer (all palpable) in the 1940′s treated only by mastectomy 30% were alive 30 years later, yet all would be treated with systemic therapy today. Why are you overtreating all these women?

    Thank you for responding to this Dr. Gorski. I’m not sure what Dr. Kopans was thinking as he wrote this. First, as you point out, it seems to try to shift the blame in overdiagnosis to pathology and overtreatment to surgery/med onc/rad onc. All physicians need to be aware of the risks, yet how can one distinguish an indolent cancer from an aggressive one once diagnosed?

    Second, I believe Dr. Kopans seems is referring to Adair et al. Cancer 33:1145, 1974 The actual 30-year outcomes of women with mastectomy for palpable tumors in the 1940′s is: 61% died of breast cancer, 26% of other causes, and 14% were alive–not 30% (ignoring those lost to followup).

    Anyway, Kopans seems to be invoking the nirvana fallacy for adjuvant therapy to cover for the apparent lack of benefit of mammography in CNBSS. Why would we treat these women today with adjuvant systemic therapy even though 40% didn’t need it? Because there is a definite survival benefit to adjuvant therapy, shown time and time again. Moreover, individual women can, if they so wish, decide to forego the adjuvant therapy based on their personal assessment of risks/benefits.

    In any case, one negative study doesn’t disprove the value of screening mammography. CNBSS brings up the question whether clinical exam might be just as effective. Kopans appropriately points out that mammographic screening technology has improved over the past 25 years. Yet, USPTF’s best estimate, taking into account all studies is that mammography saves 1 in 1904 lives between age 40-49. Is this worth it? I’m not sure. You have more years of life to save for a 40 year old than a 70 year old. Yet 1904 is a large NNI. It seems most sensible to me to select patients for screening in this age group based on risk factors.

    1. David Gorski says:

      First, as you point out, it seems to try to shift the blame in overdiagnosis to pathology and overtreatment to surgery/med onc/rad onc

      And I didn’t even get into that the way I wanted to. The post was already too long as it was. :-)

      I was more annoyed by the comment about my supposedly having seen breast cancers diagnosed by screening mammography spontaneously regress. Of course I haven’t! We treat all such cancers. That’s the point: Overdiagnosis leads inevitably to overtreatment! That remark and Dr. Kopans’ attempt to shift the blame to pathologists makes me wonder exactly what it is he thinks overdiagnosis means.

  17. Dangerous Bacon says:

    I read Dr. Kopans’ op-ed a few days ago and was struck by his claim that recommendations for changing mammography recommendations are due to a desire for “rationing” of medical care, and not to spare women from unnecessary treatment. It’s an ugly accusation, and one that fits in well with the Wall St. Journal’s previous harangues against the FDA and others who face difficult decisions about drug approval and guidelines for treatment.

    Bizarrely, it’s _Kopans_ who is protesting “inflammatory statement(s)” and “attacks” on him? If he can’t handle relatively low-key criticism, he shouldn’t be so quick on the trigger himself.

    Even more incomprehensible is Kopans’ gratuitous slam about overdiagnosis being “the pathologists’ failing”. Is he actually saying that when I and other pathologists accurately diagnose atypical hyperplasia, ductal carcinoma in situ or small low-grade invasive cancers, that it’s _we_ who are somehow responsible for whatever invasive treatment the patients get? Now we’re supposed to overlook these findings?

    The subtle mammographic changes that lead to these diagnoses are what gets the ball rolling in the first place. Maybe if more low-risk patients in their 40s don’t get imaged unnecessarily (a tough call to make), there will be fewer biopsies and less surgery, medication and other interventions that are not needed. Fewer biopsies mean less income for me as a pathologist (just as fewer mammograms will have an impact on radiologists’ income) – but I’m not about to harangue researchers for unseemly motives.

    1. David Gorski says:

      And fewer mammograms would mean less income for me, part of what I meant when I mentioned that I have every reason to support mammography screening programs. There’d be fewer surgical biopsies after an image-guided core biopsy leads to discovering lesions like atypical ductal hyperplasia and fewer lumpectomies removing 2 mm foci of DCIS. I have almost as much of a financial incentive as Dr. Kopans to leave mammographic screening guidelines the way they are, but I’ve started to come to question the need to screen under age 50.

    2. Windriven says:

      “that recommendations for changing mammography recommendations are due to a desire for “rationing” of medical care, and not to spare women from unnecessary treatment.”

      “Rationing” is a favorite WSJ bogeyman when the subject is health care. This ignores that rationing is a fact of life any time unbridled demand meets restricted supply. But under the current system the brunt of rationing is borne by, shall we say, a socioeconomic demographic that doesn’t subscribe to their $300 a year paper.

      Many of our first world trading partners enjoy excellent outcome measures for 30-40% less per capita because they spend more of those dollars euro on universal basic care and fewer on theatrical heroics.

    3. David Gorski says:

      Bizarrely, it’s _Kopans_ who is protesting “inflammatory statement(s)” and “attacks” on him? If he can’t handle relatively low-key criticism, he shouldn’t be so quick on the trigger himself.

      Oh, and I forgot: That’s exactly the reason why Dr. Kopans’ accusing me of being a hypocrite fried my irony meter. He demands civility from those with whom he disagrees, yet thinks nothing of leveling the ugliest charges against them and views criticism far milder than what he dishes out as an “attack.”

  18. brewandferment says:

    I think I have read (awhile back) some credible commentary by pathologists as to their receiving more biopsies as screening becomes more widespread, with ever more fine-grain detail available due to the use of increasingly capable equipment.

    And besides, it’s radiologists who are finding and doing more biopsies, so if there are pathologists being overloaded with breast biopsies, who’s the source of the overloading?

    So is it unheard of also that given the legal environment (whether real or perceived, I dunno) of lawsuits for missed lesions being a big threat to radiologists, that there is also a commensurate increase in hedging towards more ominous interpretation of biopsy results?

    Blaming pathologists for overdiagnosis, really?

  19. Michael Finfer, MD says:

    I find it sad that someone of Dr. Kopan’s stature would stoop to the kind of vitriol that he published in the Wall St. journal. I would have a different reaction if he had attacked the paper with his own data, but that does not seem to be the case.

    I have to put his reaction to this subject in the same category as the urology community’s reaction to the recommendation to end PSA screening for prostate cancer and the processed food industry’s reaction to the government’s attempt to drastically lower the recommended daily intake of sugar.

  20. Paul Pharoah says:

    I cannot agree with your assertion that OncotyeDx is a major advance. My criticisms are:

    1. As a clinical tool its potential utility lies in its ability to predict future events (mortality). There is a huge literature out there on the evaluation of predictive tests (predictive in the epidemiological and not oncological). Of prime importance are calibration and discrimination. There are no published evaluation of either of these measures for OncotypeDx.

    2. If the predictive performance had been evaluated, before it were used, it’s predictive performance in comparison to other models needs to be evaluated.

    I suspect that, despite its analytic validity, Oncotype Dx would add very little to a predictive model that included any one of many much cheaper was of measuring proliferation by IHC.

    http://www.predict.nhs.uk is a prognostic models that has been extensively evaluated. It would be useful to know how much OncotypeDx would improve its predictive performance, and whether that imporvement was any better than the improvement achieved by (imperfect) KI67 testing.

  21. dh says:

    From the evidence I have seen, including the Cochrane Nordic Centre reviews, and the data on over-diagnosis, it appears that screening mammography for asymptomatic women is destined to join a trash heap of screening tests that have shown absolutely no benefit for large, asymptomatic, undifferentiated populations. This includes exercise ECG’s, echocardiography, PSA testing, fasting glucose and others. Mammography is clearly grossly over-applied to women, so the only question is why this state of affairs continues to exist? Are there perverse financial incentives involved? Or academic reputations and entrenched opinions at stake? Is it so simple as the fact that people do not want to admit that their opinions were wrong? Time to wake up and smell the evidence…

    1. Andrey Pavlov says:

      @DH:

      Don’t forget that there is a sort of ideological inertia involved as well. The “War on Cancer” raised awareness of cancer when there was no talk of it in the public sphere and it became a (literal and figurative) cause célèbre ever since. At the time, one could reasonably say that indeed mammography in undifferentiated populations was an unmitigated good. It is still very much a good – it is just that the population has changed. Combine this with the not at all unreasonable mantra that early detection saves lives (it does, just not quite to the extent or as stolidly as we tend to think) and it becomes difficult to disengage from the rhetoric that decreasing the number of mammograms would directly lead to the deaths of women.

      Dr. Gorski is obviously much more qualified to comment than I, but it seems to me that a big part of what has occurred is that improvements in surgical techniques and chemotherapeutic regimens has decreased the benefit of early detection. In other words, we can detect cancers later with the same outcomes because our treatments have improved. This, combined with the very real (but initially and also reasonably unrecognized) problem of overdiagnosis has changed the landscape of screening mammography.

      And yes, there are perverse financial incentives, along with large institutions, programs, and entities erected for mammography, some ego and the inevitable difficulty of changing one’s mind, no matter who you are as well. But I think it is a disservice to not recognize that there are legitimate reasons why such a change in thought would meet resistance in addition to those less legitimate. For me, it is not so hard because I am being educated right at the moment it is happening and don’t have to actually change my mind – I just learn the evidence directly. But even Dr. Gorski has admitted that because his training was much earlier than mine, it took him some time and effort to make the change in his own mind. There is absolutely nothing wrong with that; flighty ideas are often just as bad as ones set in stone. It is always a judgment call as to how much caution is warranted and evidence needed to change one’s mind.

      However, it seems rather clear to me that there is sufficient evidence here and furthermore that Dr. Kopans’ “discussion” of the matter is less than admirable.

      1. Michael Finfer, MD says:

        From what I’ve seen in the last 30 years or so that I have been doing this, the general trend is that when something becomes easier on the patients and/or less expensive, utilization explodes. Good examples are laparoscopic cholecystectomies, arthroscopies, and image-guided breast core biopsies.

        The insurance companies, which are usually gung-ho about cost reduction, seem to me to be blind to this. They are very focused on the costs of individual cases, so when someone says I can do this for much less, they seem to count all the money they save per case and sort of miss the forest because of the trees when utilization explodes.

        I do not see a way out of this in our current system.

        1. David Gorski says:

          From what I’ve seen in the last 30 years or so that I have been doing this, the general trend is that when something becomes easier on the patients and/or less expensive, utilization explodes. Good examples are laparoscopic cholecystectomies, arthroscopies, and image-guided breast core biopsies.

          Well, yes and no. It’s true that availability tends to drive utilization, but sometimes that saves money. For instance, image-guided breast biopsies are cheaper than surgical breast biopsies. Indeed, one of the initiatives of a CQI (collaborative quality initiative) that I’m involved with is to decrease the number of surgical biopsies, the goal being over 90% image-guided core biopsies. The reasons are both quality and cost.

          Of course, for every example like that there are usually a couple of examples of more costly procedures. Don’t even get me started on breast MRI.

          1. Michael Finfer, MD says:

            True, but…

            I’ve been in one place for a very long time. My impression is that, without getting lots of help to query an obsolete and converted database that was not designed for it, we are getting lots more core biopsies, between three and five every day on average, which is way more than the numbers of needle locs that I remember getting in the old days. I have the distinct impression that there are things that would have been followed by serial mammograms that are now being cored, and we are still getting fair numbers of needle locs, less than in the old days, but still good numbers. I think utilization of core biopsies has overall increased the numbers of biopsies that we see.

            Whether that is good or not, I am not sure.

        2. Gibbon1 says:

          I’ve heard this elsewhere in general terms.

          One expects that an increase in efficiency will lower overall costs. The conundrum is that instead utilization increases exponentially.

          To wit: A thousand years ago peasants would go digging around in bogs looking for lumps of iron ore that would be painfully smelted to make precious iron. Now using modern industrial processes, the cost has come way down and we pull whole mountains apart.

          The deal with healthcare is often the decrease in mortality doesn’t match the exponential increase in costs.

      2. MadisonMD says:

        …it seems to me that a big part of what has occurred is that improvements in surgical techniques and chemotherapeutic regimens has decreased the benefit of early detection.

        Maybe; if so, early detection could be useful without survival benefit to avoid some of the toxicities of adjuvant therapy. Yet, I’m not sure this explains it. I thought the excess in cancers and pre-cancers in screened populations suggests that the modality picks up a number of indolent lesions of low malignant potential (not necessarily spontaneous remissions as Kopans seems to imply).

        Anyway, I think we have to keep in mind that the CNBSS is one study and, moreover, for age 50-59, it included regular clinical exams in the control arm.

        1. Andrey Pavlov says:

          Maybe; if so, early detection could be useful without survival benefit to avoid some of the toxicities of adjuvant therapy.

          A very good point.

          I thought the excess in cancers and pre-cancers in screened populations suggests that the modality picks up a number of indolent lesions of low malignant potential (not necessarily spontaneous remissions as Kopans seems to imply).

          Yes, this is certainly the case and I did not intend to downplay that. I was merely hoping to point out yet another reason why screening mammography seems to have less utility than may be imagined. The numbers do clearly show that there is a significant increase in early stage detection without a concordant increase in late stage cancer detection, which indicates exactly what you are saying. However, as I recall it, there is still an increase in late stage detection with simultaneous improvement in outcomes. In re-reading my comment I should not have said “a big part” – that was imprecise language and you are correct not accurate. I was more trying to relay the idea that there are multiple things at play.

          Anyway, I think we have to keep in mind that the CNBSS is one study and, moreover, for age 50-59, it included regular clinical exams in the control arm.

          Agreed. The question becomes then “is it enough?” Sometimes extremely large, reasonably well designed studies are all we can pragmatically hope to get. In this case it seems that there is other supporting and converging evidence to bolster the CNBSS data as well.

          As for the regular clinical exams – correct me if I am wrong – but my understanding was that this essentially segregated out a screening population from a “special” population. Women with palpable lumps should not be considered as screening mammography candidates. Perhaps I misread or misunderstood the data, but I thought that the (lack of) mortality benefit remained when that sort of thing was accounted for?

          1. MadisonMD says:

            As for the regular clinical exams – correct me if I am wrong – but my understanding was that this essentially segregated out a screening population from a “special” population. Women with palpable lumps should not be considered as screening mammography candidates.

            An annual and thorough clinical breast exam on a healthy woman without breast symptoms could be considered screening. This is not done routinely by all PCPs.

            You are correct that if a lump, dimple, retraction, or skin abnormality was found, the mammogram and ultrasound would then be diagnostic, not screening.

            1. Cornelia Baines says:

              “As for the regular clinical exams – correct me if I am wrong – but my understanding was that this essentially segregated out a screening population from a “special” population. Women with palpable lumps should not be considered as screening mammography candidates. Perhaps I misread or misunderstood the data, but I thought that the (lack of) mortality benefit remained when that sort of thing was accounted for?”
              I hope that my comments are relevant. There has been much criticism of the fact that women who volunteered to participate in the CNBSS received a clinical breast examination (CBE) prior to randomization. This was the consequence of research questions for the CNBSS defined at a US Workshop convened by the US NCI and the ACS in 1979. (It also allowed for evaluation of CBE interpretation in the absence of knowledge that a mammogram would subsequently be performed). There is ample evidence that randomization was successful given the distribution of over 50 demographic and risk factor variables. Further evidence is that in women 40-49, there were more positive CBE calls in the group subsequently allocated as controls. There was no segregation other than that of randomization. Because of external demands we did analyse outcomes excluding prevalent breast cancers (ie: those diagnosed at Screen 1) and this did not change our results. The analysis was the consequence of charges that we had loaded the mammography allocation with advanced cancers, all of whom would presumably have been diagnosed at Screen 1. When the adjusted analysis was performed, it did not quell our critics.
              Not relevant to the quote above is the fact that there seems to be a general acceptance that breast cancer is clinically diagnosed by finding a lump. During the course of the CNBSS it became clear to me that an important clue was asymmetry. Visual asymmetry with flattening of breast contour, sometimes no more than a centimetre (in one case this was associated with an in situ cancer) or with asymmetric thickening in the absence of a lump. And in my own case, my breast cancer manifested itself never as a lump but as a flattening of the breast contour at 6 o’ clock. So maybe we need to use eyes as well as machines??

              1. Andrey Pavlov says:

                Thank you for taking the time to comment and answer my question and clarify the issue, Dr. Baines.

            2. MadisonMD says:

              Yes, thank you for the comment, Dr. Baines. As any medical student (should) learn, inspection is part of a breast exam, and I had hoped that was implicit in my description of abnormalities above (lump, dimple, retraction, skin abnormality)… although I did not specifically indicate altered contour, nipple inversion or discharge.

              I agree that there is no issue with clinical breast exam at screening and prior to randomization. I routinely do screening physical exam, lab tests, and scans for each and every clinical trial my patients enroll in. As Rork said above, these are used to check eligibility and stratify for randomization. Your critics concerns appear unfounded. (Perhaps the only question that could arise is whether patient selection creates a mismatch between those enrolled and 40 yo women in the general population many of whom do not have the 40yo breast exam–but this seems unlikely to be a major issue.)

              I’m wondering if you would comment on whether there is reason to believe that the lack of benefit of mammography in CNBSS in the 50-59yo cohort may have arisen because well-done clinical breast exams picked up the lesions with high malignant potential? If so, this could explain different results from other studies of mammography which did not mandate the exam.

  22. Michael Finfer, MD says:

    For the record, I think that it’s important to note that not only are we talking about screening-detected breast cancers, but also we are talking about younger women of ordinary risk for breast cancer. Younger women who are known to be at high risk for breast cancer, and I am thinking of BRCA mutation carriers especially, should enter a screening protocol at an age appropriate to their medical history. This discussion does not apply to them.

    1. Andrey Pavlov says:

      Absolutely correct, Dr. Finfer.

  23. Tazia Stagg says:

    I hate it when physicians coalesce into societies for the purpose of promoting their own interests, then the professional societies act against common interests. (AMA, AUA, ACR, ASMBS…) Patients are supposed to be able to trust physicians!

    1. Michael Finfer, MD says:

      Unfortunately, physicians a have the same weaknesses as everyone else, including a fear of change and a need to stand up for their own interests. Some societies have indeed fallen into that trap.

      There are some that are outstanding examples of how groups of physicians ought to behave. I would hold up the American Society of Clinical Colposcopy and Cervical Cytology (ASCCP) as one of them. You will see flow charts on their web site detailing the current recommendations for the management of women with cervical abnormalities, some of which are significant departures from the practices of 20 years ago and which attempt to address the problems of over diagnosis and over treatment.

      Some of these other societies really need to follow their example.

      1. David Gorski says:

        Unfortunately, physicians a have the same weaknesses as everyone else, including a fear of change and a need to stand up for their own interests. Some societies have indeed fallen into that trap.

        True, but societies aren’t necessarily all bad in that there are issues in society to which the voice of physicians can constructively be added, and professional societies tend to be an effective way to do that. Are you saying that physicians should remain completely silent and apolitical? If that’s not what you’re saying, then how do physicians make their voices heard by the public, government, and industry above all the other competing organizations without forming organizations and societies of this sort?

        1. Michael Finfer, MD says:

          I am not saying that physicians should be apolitical. What I am trying to say that some organizations have taken positions that do not seem to be based upon the evidence and instead they seem to be defending a practice that generates lots of income.

          I think the urology community has crossed that line with regard to PSA screening for prostate cancer, and I think the radiologists are coming dangerously close with their stance on mammography in younger women, a position that is starting to look untenable. I will be interested to see how this all plays out and if the radiologists change their tune in the end.

          I have to say, and perhaps this is my bias, I have become wary of advocacy. It seems to be very easy for advocacy groups to cross the line from science to unchangeable belief. I suppose that is unsolvable, and one needs to simply be alert to that.

        2. Tazia Stagg says:

          I wasn’t saying that, but, now that you put it that way, yes, I would say that whenever our interests conflict with patients’, we should put patients’ interests first, such as by remaining silent, or better, advocating for patients. When our professional societies cross the line, they expose everyone to harm. There are plenty of issues that are win-win. I wish there were a formal structure for holding professional societies accountable. (Is that within the scope of the Federal Trade Commission?)

  24. Kittykitty7555 says:

    Dr. Gorski, no one who familiar with your blog could question your motives as regards screening mammography. Two points:

    First: Dr. Kopans may be especially sensitive to any analysis that comes from you because you actually care for women who have breast cancer. For years has been “howling” about the fact that the USPSTF panel that revised breast cancer screening recommendations in 2009 contained no breast cancer surgeons or oncologists. But screening is a primary care issue. Surgeons and oncologists do not generally sent their breast cancer patients for screening mammography.

    Lastly, Dr. Kopans is a zealot when it comes to screening mammography. His beliefs are faith-based, so science cannot shake them.

    Very brave of you to risk his wrath by disagreeing with him. You are the man.

  25. rork says:

    Small stats notes:
    “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”.
    If I roll a pair of dice and get doubles three times in a row, is it indisputable I was cheating somehow? No.
    “A fundamental rule for an RCT is that nothing can be known about the participants until they have been randomly assigned” – maybe he doesn’t know much about clinical trial design either. Often you randomize within strata. For example forming groups according to age, and then randomizing within each group, to better make sure you don’t accidentally get more younger people in one arm of the trial. You also check to see if the patient qualifies to be enrolled in the study – men may not have qualified. Often the list of things needed (or forbidden) to qualify is very long. It is good to have a foolproof way of randomizing though (sealed envelopes, computer algorithm, or third party are examples).

    One more note, about prognosticating. Just cause I know one person is more likely to die from their disease than another does not tell me what I should do about it.

    1. Andrey Pavlov says:

      Good points rork.

      When I was at the ATS conference last year Derek Angus was talking about how to improve the study methodology for sepsis research. The problem is that the effect sizes are relatively small such that large populations are needed to suss out differences. He gave the example of a hypothetical drug that would lower ARDS mortality by half still requiring ~10,000 patients to be powered adequately, given the known prevalence and mortality of ARDS. He discussed a sort of staggered and then funneled RCT design (which I admit I don’t fully apprehend… yet) wherein study populations are stratified and then randomized, then sub-populations within that group are re-stratified and then re-randomized, with new patients entering in at the 2nd strata to improve the power of the study. In essence, a means by which to change the population you are dealing with such that the prevalence of the entity of interest is higher (“concentrated” if you will) successively to improve the power of the study without needing such that a huge n is not necessary.

      Kopans complaint about the trial design sounds to me like something a med student or early resident would say before (s)he learned about more complicated (yet valid) study designs. It also sounds like he would believe that roulette tables in Vegas are rigged when the board comes up with 15 blacks in a row, but instead of betting on red thinking that it must be more likely to come up on the next roll, bet on black because it is “indisputable” that the table is rigged to come up with more blacks than reds.

  26. MadisonMD says:

    It also sounds like he would believe that roulette tables in Vegas are rigged when the board comes up with 15 blacks in a row, but instead of betting on red… bet on black.

    I would definitely go with black in this scenario. If rigged, I win. If not, 50%.

    3 in 100,000 is unlikely, so decent chance its rigged.

    1. Lytrigian says:

      It’s not quite 50%, because of the 2 green slots, yet it only pays 1:1. That’s where the house edge comes from. Payoff odds are always just a little smaller than odds of winning.

      3 in 100,000 is unlikely, but it must happen sooner or later.

      1. CHotel says:

        Paraphrasing slightly, as I can’t remember the exact wording:

        “But of course, things that have a very *small* chance of happening, happen all the time! To think that your thing is somehow special is to greatly underestimate the number of things that there are.”

        – Tim Minchin

  27. Andrey Pavlov says:

    MadisonMD:

    Always bet on black

  28. Gary Paulson says:

    one thing never really mentioned in the over diagnosis of mammograms is the medico legal part. I think mammograms are the single most potentially litigated imaging study we do. The natural tendency is to over read every potential finding. No study is perfect and if we allowed some uncertainty in our lives without the threat of a lawsuit I think I would be doing or arranging for a lot fewer biopsies than I am currently (for the past 25 years). By the time a woman has been through a screening mammogram, diagnostic special views, an ultrasound and the recommendation for an MRI— that won’t be paid for by insurance— and gets to me for a surgical opinion—she is almost ready to have bilateral mastectomies just to get a night’s sleep. It is difficult to “stop the train” heading for a biopsy at that point.

  29. Newcoaster says:

    As a family doc I’m still trying to figure out what to tell patients with regard to screening. It is causing a lot of angst and confusion in patients, similar to the conversation I have with men about the utility of PSA testing.

    Dr Kopans comments, are similar to those of other radiologists I have talked to, and strike me more as turf protection and being overly defensive. He also seems blissfully unaware of making his own “appeal to authority ” by signing his email with all his various credentials as a form of intimidation. Surprised he didn’t put his high school diploma or SAT score in there for good measure.

    Keep up the good work David

  30. Marty Martelle says:

    I blame this whole debacle on my fellow “communist” Canadian citizens who do research north of the border, maybe the cold air is impacting our thinking :)

    1. Newcoaster says:

      When this article was first reported on CNN online a few months ago, many of the commenters dismissed it simply BECAUSE it was a Canadian study. Us damn commie Canadians and our evil socialized medicine couldn’t possibly do real science like ‘Mericans

  31. Robert S. says:

    Somehow I doubt Dr. Kopans vitriol would have risen so high or so fast if the study suggested HE didn’t have to get a camera shoved up his backside as often. I recomend thrice yearly colonoscopies for the good doctor, can’t be to safe after all (there might be another craniorectal inversion to fix).

  32. Elizabeth (Aust) says:

    I found the Nordic Cochrane Institute’s summary on the risks and benefits of mammography very helpful; I’ve declined breast screening. The NCI is a not-for-profit, independent medical research group, their report was released over a decade ago, but most women haven’t seen the summary. Too many have a vested interest in women’s cancer screening and certainly don’t want the evidence getting in the way of their awareness drives and pushing to achieve govt-set screening targets. Screening is big business.
    Most women here are still in the dark, the serious risk of over-diagnosis and uncertainty of benefit was only mentioned to women here about a year or so ago. Prior to that, discussion was safely locked behind pay walls, in medical journals. When women hear for the first time that mammography is not all it’s supposed to be, they tend to ignore it, but the same studies keep appearing and now more women are questioning cancer screening. It’s disgraceful that informed consent has been largely ignored in women’s cancer screening, (consent itself is often violated with cervical screening)
    Breast Screen here keep pushing for their govt-set target, serving up IMO, a one-sided presentation. The cat is out of the bag though and they have no chance of reaching the target, so what do they do, they plan to extend the program to include women up to the age of 74.
    I can only imagine this will lead to more over-diagnosis.

    It is SO important that these programs are properly and independently assessed with RCTs before introduction, are regularly reviewed and stay current with new evidence and MOST importantly, are kept far away from the perverse influence of vested and political interests. They must also respect both consent and informed consent (NO targets etc.) Screening should be an option, an informed decision, not an expectation or order.

    Professor Michael Baum, UK breast cancer surgeon, is an amazing advocate for informed consent. His article in the BMJ last year concluded the risks with breast screening exceed any benefit when you factor in those who die from heart attacks and lung cancer after treatments.

    I read over the same names that angrily reject anything that threatens screening, in my opinion, they’re protecting screening, not women. If they really cared about women they’d be just as concerned that study after study says the same thing or at the very least be respectful of our right to all of the information and leave the decision to us.
    Also, those who use inflammatory language, trying to scare women into compliance or cause confusion are instantly dismissed, “more women will die if they don’t screen” means IMO, the speaker cannot meet the evidence that threatens screening (and their self-interest) and so lashing out is their response. They know some women will continue to screen while there “appears” to be confusion about the evidence or through fear or from the mistaken belief this is all about cost-cutting.

    I’d urge every woman to head over to the NCIs website and start reading and doctor-shop, find someone ethical and respectful. My file has been marked, “No screening” so no valuable consult time is wasted discussing the matter.
    There are great doctors out there, you just have to look for them, those who coerce should be reported, those who pressure, lecture, try to scare you etc. should be avoided. For too long the profession has just expected women to file in like ignorant sheep, that attitude needs to change and IMO, that starts with individual women refusing to accept that sort of paternalistic and insulting treatment.

    I do have my blood pressure checked every year or so, the value of BP screening was made clear after one small RCT. I’m still researching bowel screening, I don’t just accept recommendations, but do my own research and consider risks v actual benefits, is this test really in MY best interests?

    IMO, women’s cancer screening has not followed the evidence or put the interests of women first. So many women have been harmed and the tragedy is that almost all of the damage was avoidable with evidence based screening and some respect for informed consent.

  33. Maria says:

    I have wanted to reply to this for a while, part of the problem is that the message that early detection is a cure had completely over whelmed any other message.

    The way I see it is that early detection may/can lean to better out comes and less treatment, but that not as pity a message as early detection is a cure.

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