A FORCE against disease mongering

Have you been over to The Oransky Journal lately? If not, go and see what is happening there. What is happening is a microcosm of the larger debate we are having about detection and diagnosis of real disease versus overdiagnosis of phantom conditions whose treatment is worse than anything that the potential disease may deliver.

The issue is as follows. In his talk at TEDMED in April, Ivan gave an excellent and measured presentation about the folly of pre-disease classifications and the harm they can bring. As my readers are well aware, this is the subject of great interest to me -- after all, it is a travesty that contact with the so-called "healthcare" system is the third leading cause of death in the US, and that overtreatment costs us at least 10 cents of each healthcare dollar, and probably much more (you will find a slice of my posts on this issue here). So, Ivan's talk was timely and cogent.

After he posted the talk on his blog, he received a letter from a group called FORCE (Facing Our Risk of Cancer Empowered) who, as it turns out, coined the word "previvor," one of the many words Ivan used to illustrate the philosophy of disease mongering. The letter voiced a vigorous objection to Ivan's use of the word to "misunderstanding" its meaning. But what really happened?

Apparently, "previvor" defines a group of people who are at a heightened risk for cancer, but have not yet been diagnosed. It seems that the majority of FORCE's constituency consists of women with the BRCA gene mutations, which put them at an extraordinarily high risk of several cancers, most notably breast and ovarian. Moreover, these cancers tend to occur at an early age, and are generally quite a bit more aggressive than those not associated with these mutations. We are not talking a trivial rise in the risk either; BRCA1, for example, raises one's lifetime risk for breast cancer to about 80%! To mitigate this risk, many women with these types of mutations undergo prophylactic mastectomies and oophorectomies. These are life-changing events, and their genetic make-up hangs like a Damocles' sword over the offspring of these women as well. So, what's the problem with using whatever word suits them?

The issue is the group's definition of this neologism "previvor." As quoted in Oransky's post (italics mine):

“Cancer previvors” are individuals who are survivors of a predisposition to cancer but who haven’t had the disease. This group includes people who carry a hereditary mutation, a family history of cancer, or some other predisposing factor. The cancer previvor term evolved from a challenge on the FORCE main message board by Jordan, a website regular, who posted, “I need a label!” As a result, the term cancer previvor was chosen to identify those living with risk. The term specifically applies to the portion of our community which has its own unique needs and concerns separate from the general population, but different from those already diagnosed with cancer.

So, the definition is quite broad, as you can see, especially the "some other predisposing factor." Who doesn't have one? Just by virtue of being alive we have predisposing factors to many diseases, including cancer. And aging is one of the strongest predisposing factors to cancer as well. The concern is that a broadly defined term like this plays right into our national paranoia about our health and our enthusiasm for screening as the primary mode of prevention. And if you really don't feel well informed about why screening is not all it's cracked up to be, I urge you to dig through the annals of this site thoroughly (if you don't have much time, you can get a solid primer on the issue from my book). In my view, given the extent of the harm from overdiagnosis and overtreatment, Oransky's call-out of this word in the ultra-visible forum of TEDMED was a public service.

And indeed, it turned out this public service has gone well beyond just delivering the information. The discussion that ensued over the last couple of days with FORCE has shown what this organization is made of. An 80% lifetime risk of breast cancer is a grave matter, and the group is an important force in advocating for these patients and supporting their families. But as it turns out, it stands for even more than that. I commend Dr. Friedman, the Executive Director of the group, for being open to narrowing the definition of the term "previvor." This willingness signifies a real desire to do the right thing not only for her constituency, but also for the public at large. Even more, she should be proud that her organization is taking a stand against disease mongering.

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More on "mammography saves lives" story

A story in HealthDay with the title of "Two Studies Find Routine Mammography Saves Lives" talks about studies presented at the annual meeting of the American Society for Clinical Oncology (ASCO) European Breast Cancer Conference (EBCC). The studies, both from the Netherlands, allegedly showed that mammography does indeed save lives. If true, these data would contrast with the preponderance of evidence that has stirred up such a ruckus recently about the utility of mammography, complete with references to rationing and death panels. But let's look at what's reported in today's story more closely.

Cutting through all the definitive bravado, here is a little piece of science that was reported:

Compared with the pre-screening period 1986 to 1988, deaths from breast cancer among women aged 55-79 fell by 31 percent in 2009," Jacques Fracheboud, a senior researcher at the Erasmus University Medical Center in Rotterdam, said in a meeting news release. We found there was a significant change in the annual increase in breast cancer deaths: before the screening program began, deaths were increasing by 0.3 percent a year, but afterwards there was an annual decrease of 1.7 percent," he added. "This change also coincided with a significant decrease in the rates of breast cancers that were at an advanced stage when first detected.

Note, the reference is to deaths from breast cancer without any mention of all-cause mortality. (You can read about why the latter is important here.)

The report next states that over the first 20 years of the screening program

... 13.2 million breast cancer screening examinations were performed among 2.9 million women (an average of 4.6 examinations per woman), resulting in nearly 180,000 referral recommendations, nearly 96,000 biopsies and more than 66,000 breast cancer diagnoses.

So, doing the math, I come up with about 31% false positive rate at the biopsy stage (that's 96,000 biopsies minus 66,000 positives for cancer, all divided by the 96,000 total biopsies). If we use the 180,000 "referral recommendations" as our denominator of all positive tests, and stick with the 66,000 true positive rate, then the false positives grow to (180,000-66,000)/180,000 = 0.63, or 63%. If we spread the 33,000 false positives over the 13.2 million examinations, that equates to 0.25% chance for a false positive. Yet the report goes on to say that (emphasis mine):

For a woman who was 50 in 1990 and had 10 screenings over 20 years, the cumulative risk of a false-positive result (something being detected that turned out not to be breast cancer) was 6 percent.

Six percent? This is clearly a place where my high school math teacher's mantra of "show your work" is applicable.

The next piece of information that I would like to understand better is this:

Over-diagnosis (detection of breast tumors that would never have progressed to be a problem) occurred in 2.8 percent of all breast cancers diagnosed in the total female population and 8.9 percent of screening-detected breast cancers."

How exactly was this computed? Again a case for "show-your-work."

And then there is this (emphasis mine):

Regular screening "decreases deaths by over 30 percent, [with] limited harm and reasonable costs. Additionally, cancers are detected at an earlier stage, which means not only decreased mortality but also morbidity; the patient may not have to have chemotherapy or a mastectomy," she noted.

OK, so, if I got it right, it is breast cancer mortality that is decreased by 31%, not all-cause mortality. This really should have been spelled out more clearly, not to mention that the actual, or absolute, reduction likely pales in comparison to this relative drop. And what about diagnosing earlier stage disease? Lead time bias, anyone?

The second study was a computer model, and I will not go through it at this time as I need to move on to other work. But you get the picture: the numbers given in the report are limited and at times they don't add up. Mixing up cancer mortality with all-cause mortality leads to erroneous conclusions. And finally, forgoing reporting on the absolute risk reduction in favor of the inflated relative reduction is not helpful for understanding the true risks involved.

One final thought: Yes, I do have cognitive biases, and it is difficult for me to avoid them. I happen to fall into the camp that thinks screening for sublclinical diseases, at least in our current technological setting, is disease mongering. At the same time, I would like to think that if the data really showed a significant benefit without great risks, I would give them a second look.

The bottom line is this: at least for me, the report confused the issue more than it has clarified. Perhaps the study, once published, will answer all of the questions that I have posed adequately. But at this stage, it is a shame that such strong statements as...

"These results show why mammography is such an effective screening tool," said one U.S. expert, Dr. Kristin Byrne, chief of breast imaging at Lenox Hill Hospital in New York City. She was not involved in the new research.

 and this...

"We are convinced that the benefits of the screening program outweigh all the negative effects," Fracheboud said.

 ... are not backed up by appropriate evidence.

h/t to @ElaineSchattner for the story


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Thank you for your support!

The changing language of medicine

A very close friend of mine has breast cancer. It is a very small tumor, diagnosed on an annual mammogram, requiring confirmation with a breast MRI. She had a lumpectomy today, and I was with her at the hospital. This proved to be an enlightening experience.

To put things in perspective, when I was in training and in practice (yes, in the dark ages when we were expected to stay awake AND care for patients for over 48 hours at a time every 3 days), we had not heard of patient-centered medicine. I learned that my role was to diagnose, come up with a plan of action and convince the patient at any cost that my plan was the correct one. To be sure, I always tried to do this in a nice way, but would get a bit impatient when my judgment was questioned. This is the behavior modeled for me by my elders and others whom I respected.

Well, that was then. Having had quite a few years to reflect on the practice of medicine in the context of our healthcare system, I have learned just how misguided this attitude is. And, being a Sagittarius, I cannot fathom how this universal truth is escaping others. Yet escaping it is. This became obvious to me today.

My friend had to have a nuclear medicine test prior to her lumpectomy to define the extent of axillary nodal involvement. She had been told that this is an arduous and painful experience that cannot be mitigated with pre-medication. She was also informed that asking the radiologist to deliver the radionuclide slowly rather than as a rapid push might reduce the sensation. So, my friend, who is herself a physician, was prepared for a civilized and simple conversation with the practitioner. Yet, this is not what transpired. You would think that being asked to deliver the chemical slowly is not such a big and unreasonable request. Well, if you thought this, you were wrong: evidently this was such a big ego blow to the radiologist that she felt compelled to respond snidely, "Well, OK, I am not going to fight with you about it". Now, this is off-putting under the best of circumstances. Imagine being about to go to the OR to have a cancer removed from your breast, and having this snide come-back thrown at you. And why? What is the harm in going along with the patient's request if it makes no difference in the end-result of the test? Is it really necessary to diminish her in such a blatant way?

Well, this physician was of a similar vintage to me, and I can only imagine that she came into practice before patient-centered care became the standard. In her mind, as in mine in those distant days, my involvement with the patient's care was not really about the patient necessarily, unless they fell in line with my recommendation. The shameful fact is that my ego was much too fragile to allow a discussion or questions about my considered course of action. How could they go against my years of training, deep knowledge and their best interests? I cannot say for sure, but it is likely that my friend's radiologist was cut from similar cloth. And what is so obvious to me today has not yet been assimilated by so many of my colleagues, including this person.

As I have said before, the new direction for medicine cannot be what I am used to in real estate: "I do not have what you need, but I will show what I do have". The new direction in medicine must undoubtedly be one where the patient is the center of the encounter, and it is the patient's interest rather than the doctor's ego that must be protected assiduously.

Lest you think that the entire hospital experience was negative, let me be clear: of all the people taking care of my friend, the radiologist was the sole disappointing exception. Her surgeons, anesthesiologists, nurses and ancillary personnel went above and beyond my expectations. I was amazed by the level of civility, good humor, politeness and real involvement everyone exhibited -- it was truly different from my days on the wards and pleasantly eye-opening. It even gave me some hope for the future of medicine in the midst of my normally nihilistic ruminations.            

The great poet Rumi said that changing language can change our life. Well, when the recovery room nurse said to my friend "Let me know when you feel that you would rather rest at home than here", I was overcome with warmth and good will. The language of medicine does seem to be changing. And if it continues in this vein, perhaps it will change our lives.

USPSTF recommendations: Demanding manipulation from science

The recent uproar over the new screening mammography recommendations got me thinking about a lot of stuff. One of the lessons cited by some journalists and pundits is on how potentially volatile information should be presented to the public. The USPSTF was excoriated by critics not only for what it said, but how it said it. While the objections over the former can be dismissed as ravings of loud and poorly informed voices deliberately trying to hijack public opinion, the latter criticism is more insidious.

Some intelligent and balanced observers noted that the USPSTF really should have foreseen the fallout and laid the groundwork to make the sting of the recommendation less pronounced. In the corporate world this is called "making the rounds". This means that, when you have an idea, it is not enough just to present it on its merits in a group forum. Indeed, you must go around to those whose opinions matter and get them to sign on to your idea before you make it public. In this way, by furthering your relationships, you manipulate the outcome in your favor. This can take countless hours, but this is how things generally get done in the world of business.

The world of politics is similar, in that many reforms and decisions are dependent on behind-the-scenes deal-making between politicians. These clandestine transactions, the theory goes, assure the appearance of a successful outcome in the light of day. And a victory necessarily begets other victories.

Well, to be sure, science and academia are not immune from such politicking and manipulation. In fact, I have heard some assert that our academic institutions are the most politically charged enterprises, even more so than business and politics. So, in that respect, it is not unreasonable to expect some round-making prior to spilling the mammography beans. But what if we question this premise? What if we insist that science remain the last frontier shielded from political influences? I would argue that this should be our only stance on science, be it climate science or medicine. Science should be judged on its merit only, and not on its political ramifications.

In a society where business and political message machines spend countless dollars on market research surveys to package their manipulations to get us to follow their political and consumerist directions, the public is now angry that the USPSTF, a scientific body, did not take the time to effect an elaborate manipulation scheme to get the loud dissenters, and the rest of us, on board with their recommendations. Is it not outrageous that we, American adults, expect, and even demand, such manipulation instead of the straight unadulterated truth?

This is a sad reality of our time, following decades of indoctrination by marketers, educators and other "experts", to become compliant little consumers that we are today. How easily we are stirred into a rage by callous reporting and special interest demagoguery is telling. We are a mirror-mirror-on-the-wall society: we will not tolerate any truth that does not fit our conveniently preconceived notions of specialness and entitlement. And while this attitude gives us a peaceful soporific feeling one gets following a psychotic rage, it will make it that much more painful when this consumerist fog is replaced by the reality of shortages, as our cheap energy supply dwindles. Unfortunately, by then, it will be too late for the truth to set us free.

There is still time, though! Turn off the television, stop listening to and reading mass-produced messages designed to make you a quiet lemming on its way off the cliff. Focus closer to home, build your local community. And, yes, talk to your doctor about your mammography concerns -- you will surely walk away with a more satisfying conclusion and a feeling of self-determination.

Does number needed to treat help with rational decision-making?

Here is the perfect illustration of how irrational and emotional the issue of breast cancer is. Take the current maelstrom over the USPSTF's new screening mammography recommendations, which now advise against routine screening for women between the ages of 40 and 49 and change the recommended interval for women 50 to 74 years old from yearly to biennial screening. Let's focus on the number needed to invite (a diagnostic test's analogue of the number needed to treat, NNT). The NNT of mammography for a woman in her 40s is nearly 2,000, meaning that we need to screen 2,000 women to prevent 1 breast cancer death. Similarly, among women in their 50s, this number is about 1,300.

Let's not even talk about what the implications of over-diagnosis and over-treatment may be in all these women; I have written about this in the past here and here. Let's just focus on costs. An average cost of a mammogram is ~$100. So, multiplying the 2,000 NNT by $100 yields $200,000 per life saved. Again, if this were the only cost (and again, we are staying away from costs of repeat testing of false positives, invasive diagnostic testing and potential over-treatment and its attendant complications), I would say that it might be reasonable, especially when you take into account the number of years that can be saved for a woman in her 40s.

Now, let's look at the only therapy on the market that reduces mortality in patients with severe sepsis, drotrecogin alfa (activated). Its NNT is 16. That's right, it takes treating 16 patients to prevent 1 sepsis death. Given that a course of this drug costs ~$10,000, the cost to save 1 life is $160,000, or not that different from screening mammography in the 40-49 age group. Though the drug cost is 2 logs higher than that for mammography, the total population is about 2 logs less, so the total costs may be comparable. Yet, there is no battle going on for the use of drotrecogin alfa, and is has been all but abandoned by the ICUs in the US, mostly due to its expense.

So, without making any kind of a value judgment or a politically motivated statement, is this not a double standard? Is this not irrational and selective? Is this a result of a disease with a strong lobby versus one that does not have a patient advocacy group (mostly because 50% of these patients die in the hospital)? Or is it that mammography is perceived as prevention while drugs are disease treatment?

I am really not sure what the answer is to this apparent double standard. I also will refrain from proselytizing about the willingness to pay and whose money and the potential harm and even death due to over-diagnosis and over-treatment. But people, we do need to confront our irrational demons of inconsistency. On the other hand, if we cannot make these allocation decisions rationally as individuals, don't you think we would benefit from a body whose sole purpose it is to do this transparently and in an evidence-based manner?            

Is breast cancer really the WORST enemy?

I got a chain e-mail from a good friend of mine urging me to get my screening mammogram done. The message contained cute comics about mammography (mostly about the lasting effects of squishing the boobs, you can imagine), and at the end it had the following message:

Mail this to 13 other women. Now, don't break the chain! One female broke the chain, her plumbing became so bad, she now has an outhouse! OK gals, now that you have had your laugh, remember... Breast Cancer Awareness... Go have those boobs checked out and stay healthy! Pass the message on to your mothers, sisters, daughters, aunts, cousins, friends, and even your enemies. Because the WORST enemy is Breast Cancer.

Now, by now you,my reader, know that I am a great skeptic of over-diagnosis and over-treatment; I think it causes more harm than good, though we have not really bothered to quantify the harm yet. But a recent study from Europe fueled my fires on the mammo front. This study, a systematic review of the literature on the subject, concluded that about 1 in 3 cancers in a screened population is an over-diagnosis. In an accompanying editorial, H. Gilbert Welch from Dartmouth, a perennial skeptic of the "more is better" approach, provided a sober view of the dilemma:

Mammography is one of medicine’s "close calls"—a delicate balance between benefits and harms—where different people in the same situation might reasonably make different choices. Mammography undoubtedly helps some women but hurts others. No right answer exists, instead it is a personal choice. (emphasis mine)

Dr. Welch, one of the foremost experts on over-diagnosis in mammography, in fact provided this very useful, in my opinion, table:

Draft balance sheet for screening mammography in 50 year old women*

Credits Debits 1 woman will avoid dying from breast cancer 2-10 women will be overdiagnosed and treated needlessly 10-15 women will be told they have breast cancer earlier than they would otherwise have been told, but this will not affect their prognosis 100-500 women will have at least one "false alarm" (about half of these women will undergo a biopsy)

*For every 1000 women undergoing annual mammography for 10 years

This tally is chilling, given that the end-result is that, to avoid 1 breast cancer death, 2 to 10 women will be treated unnecessarily with disfiguring surgery, toxic chemo and radiation therapies, and 100 to 500 others will be subjected to follow-up testing, some of it invasive. Now, you may be saying that it is all worth it to avoid dying from breast cancer. Unfortunately, what we do not have a solid idea about is how much harm, in the form of complications and deaths from the unnecessary work-up and treatment, comes from this "better-safe-than-sorry" approach. We also have very little knowledge of the long-term effect of the radiation exposure from mammo. 


So, the bottom line is that, if a woman decides against the current dogma to have annual screening mammography, don't make her into a pariah -- she is exercising her good judgment. Peer pressure in this situation is not only unwarranted, but may be detrimental. We as the medical and public health profession need to start developing a much more nuanced message about cancer screening in general, and mammography in particular. There is too much evidence now that one size does not fit all.