Understanding the Mammogram Paradox

There are lots of good reasons to try and follow a healthier diet–you lose weight, you feel good, but the main reason–to live a longer, happy, productive life.  Sounds good, right?   And though it may sound deceptively easy, the devil is in the details.   Welcome to the Nutrition Facts podcast.  I’m your host, Dr. Michael Greger. 

In the third of our podcasts on the efficacy of mammograms, we try to understand the mammogram paradox.  What is that, you may ask?  The mammogram paradox is that it’s the women who are harmed the most who are the ones who claim the greatest benefit.  Here’s the story.

Over the last few decades, our radiation exposure has nearly doubled, thanks almost exclusively to medical sources, such as CT scans. We’ve known that higher-dose radiation, like CT scans and angiograms, can cause breaks in our DNA, but now we know that mammograms can too. You can find X-ray induced DNA damage in white blood cells drawn from women right after her mammogram. 

That’s amazing they can find evidence of DNA break; I mean, how much blood is there in the breast in the first place? And then, you squeeze it out during the procedure, and then it mixes with the unexposed blood from the rest of the body, and you can still pick up the DNA damage circulating throughout her system. So, what they found “underestimate[s]” the DNA damage in the breast tissue itself.

But, doctors tell women, “There is nothing to worry about.” Just a few extra cases of breast cancer are caused by mammograms. Wait; what? Mammograms causing breast cancer? Yes. The “risk of radiation-induced breast cancer” from modern, low-dose digital mammograms depends on how often you get screened, and at what age you start. “For a [group] of 100,000 women…screened annually from age 40 to 55 years and [every other year until] age 74…, it is predicted that there will be 86 cancers induced and 11 deaths due to radiation-induced breast cancer.” Meaning they estimate 11 of those women will die from breast cancer that they would never have gotten if they decided not to get mammograms—not expose themselves to that radiation. They even calculated the lifetime risk of developing a radiation-induced breast cancer after just getting a single mammogram.

Women with large breasts may carry additional risk, because their mammograms may require additional views, and the greater radiation dose is expected to translate into “a greater risk for radiation-induced breast cancer and breast cancer death”—as much as triple the lifetime attributable risk of developing breast cancer because of the mammogram radiation exposure.

The earlier one starts screening, the higher the risk as well, since there’s more time for a cancer to grow. This comes up for women with BRCA gene mutations, for whom screening is sometimes recommended starting in their 20s. But, at that age, mammograms may cause as many breast cancer deaths as they prevent. A net benefit would be expected at 35 years old, though, and likely the same for women without BRCA mutations. Yes, “The risk of radiation-induced cancer from mammography is not negligible, [but] the potential for mortality benefit is generally considered to outweigh the risk of death from radiation-induced [breast cancer] attributed to mammography screening”—”a benefit-to-risk ratio in lives of” 10:1 or more.

Now, these estimates on how much breast cancer mammogram X-rays may cause relies “heavily on data from the atomic bomb survivors,” who were exposed more to gamma rays, which are like high-energy X-rays. But, it turns out the lower-energy X-rays used in mammography are even worse—”approximately four times…more effective in causing mutational damage than higher energy X-rays.” And, “[s]ince current radiation risk estimates are based on the effects of…gamma [rays], this implies that the risks of radiation-induced breast cancers [from] mammography X-rays” is four times worse than previously estimated. But, even if that were true, the benefit-to-risk ratio would still favor mammograms, “concern about radiation exposure should not prevent [a woman] from undergoing life-saving mammography screening.”  But, “No trial has ever shown an overall mortality benefit from screening mammography. Thus, if there is a detrimental effect of radiation exposure from mammography, even a small effect could offset [the benefits].”

The most ironic harm from mammograms is that in extremely rare cases they may cause breast cancer. 

In our next story, we discover the risk and benefits ratio of the radiation that comes with every mammogram.  While false-positive results, pain during the procedure, and radiation exposure may be among the most frequent harms associated with mammogram screening, “the most serious downside” is now recognized to be something called “overdiagnosis”—so serious as to raise the question: “does it make [the whole thing] worthless?” The value of doing routine mammograms at all is being questioned due to overdiagnosis, which is “the diagnosis and treatment of breast cancer that would never have become a threat to a woman’s health, or even apparent, during her lifetime.”

See, people “think…that once you have a cancer cell in your body, it will progress, predictably and inevitably, to a terrible death.” And “that[’s] simply not true of most cancers.” “Some cancers [may] outgrow their blood supply,” become starved, and wither away. “[O]thers may be recognized by [our] immune system and…successfully contained, and some are simply not that aggressive in the first place.” Meaning, yeah, it may continue to grow unchecked, but so slowly that it would be like 200 years before it was big enough to cause any problems. And so, in effect, you die with your tumor, instead of from your tumor.

Indeed, if you do autopsy studies of young and middle-aged women who just happened to die in a car accident or something, 20% of them had cancer in their breast. So, like one in five women are walking around with breast cancer. Now, that sounds a lot scarier than it is, since at that age range, the risk of dying from breast cancer is less than 1%. In fact, your risk of ever dying from breast cancer in your lifetime is less than 4%, which goes to show that many of these cancers they found incidentally—in fact, most of them—would likely have just fizzled out on their own.

The problem is that we continue to have a 19^th-century definition of cancer, dating back to the 1860s. See, cancer is defined by what it looks like under a microscope, not by what its subsequent behavior is. So, yeah, using that definition, one in five of these women technically had cancer, like this 30-year-old here. But, that doesn’t necessarily mean it would go on and do anything.

The question then becomes: If it’s so common, do you even want to know about it? If it’s going to progress and cause a problem, then definitely; catching it early could save your life. But, if it’s never going to grow, if it’s going to remain microscopic, then finding it could actually be bad for you. They’d be like look, you have cancer; we have to treat it—surgery, chemo, radiation—whatever it takes. Then, you’d suffer all the physical effects of treatment, the psychological hell of fearing for your life, all completely unnecessarily, if, in fact, it was never going to cause a problem. That’s overdiagnosis.

These kinds of car accident-type autopsy studies show that between 7 and 39% of women ages 40 through 70 are walking around with tiny breast cancers. 30 to 70% of men older than 60 have prostate cancers, and up to 100% of older adults have microscopic cancers in their thyroid glands. Yet, only point one percent—one in a thousand, ends up suffering or dying from thyroid cancer. Normally, it just sits there, and doesn’t do anything. Likewise, even though the majority of older men may have tiny cancers in their prostates, or a significant number of women in their breasts, the lifetime risk of death or cancer spread is only about 4%. So, if you had a magic wand that could pick up cancer with 100% accuracy, and waved it in front of people, your overdiagnosis rate—the probability that the prostate cancer you’d pick up would have turned out to be harmless—is like 90%, and nearly every single thyroid cancer, and a significant proportion of breast cancer cases. That’s why screening for these cancers can be tricky, or even potentially dangerous, since, in many cases—sometimes most cases—you would have been better off if they had never found it.

Now, this is not true for all cancers. “There is little evidence of overdiagnosis [for] cervical or colorectal cancer,” for example. Those cancers do seem to just keep growing; and so, the earlier you catch them, the better. So, institute Pap smears, and cervical cancer death rates plummet. And, just a single sigmoidoscopy between the ages of 55 and 65 may decrease one’s risk of dying from colorectal cancer by up to 40%—whereas some studies show that even getting mammograms every year don’t appear to reduce breast cancer mortality at all. But, if we assume a 15% drop, and a 30% overdiagnosis rate—which is what most studies have found—then that would mean for every 2,000 women invited for mammograms for 10 years, one will have her life prolonged, and 10 healthy women would be overdiagnosed. In other words, they “would not have had [a] breast cancer diagnosed” if they had skipped screening, but were instead “treated [for breast cancer] unnecessarily.

And, about a thousand would have gotten false alarms, which can be stressful while you wait for the results. But “[t]he harms caused by [becoming a cancer patient unnecessarily can be] lifelong,” and even mean a shorter life. It’s “important to be aware that some of the [needlessly treated] women will die from that treatment.” For example, radiation treatments can’t help but penetrate down into the heart as well, increasing risk of the #1 killer of women: heart disease.

This raises questions about doing routine mammograms, period, as it “converts thousands of healthy women into cancer patients unnecessarily”—some of whom may not make it out alive. Ironically, though, those who do become mammography’s biggest cheerleaders, thinking mammograms saved their life. The mammogram found a cancer didn’t even know you had, and yeah, the treatment was rough—surgery, radiation, drugs, but it worked; life was saved. Thank God she got that mammogram; you should, too.

Whereas actually, the more likely scenario—in fact, maybe the 10 times more likely scenario, is that the treatment didn’t do anything, since the cancer wouldn’t have hurt you anyway. So, you went through all that pain and suffering for nothing. That’s the crazy thing about mammograms; the people who are harmed the most are the ones who claim the greatest benefit.

Nine out of 10 women don’t realize that some breast cancers would never have caused any problems (or even become known in one’s lifetime). This is an issue DCIS (ductal carcinoma in situ) has brought to the fore.

The whole point of cancer screening is to “detect life-threatening disease at an earlier, more curable stage.” So, an “[e]ffective cancer-screening program…[would] therefore…increase the incidence of cancer detected at an early stage [because you’d find all these tiny cancers you would have missed before] and [therefore] decrease the incidence of cancer presenting at a late stage”—because you would have cut out all the little cancers you found, pulling them out of circulation.  But, that’s not what appeared to happen with mammograms. As mammography ramped up in the ‘80s, the first part happened: the diagnosis of early cancers shot up. And so, what we’d like to see is like a mirror image of this, going the other way, for late-stage cancers. If you caught it early, it wouldn’t be around for late. But, that didn’t happen. Late-stage cancer incidence didn’t seem to drop much at all.  Another way to look at this is to compare mammogram rates around the country. The more mammograms you do, the more heavily screened the population is, the more early cancers you pick up. Great. And late, advanced disease should go down too, right? But, it doesn’t. We’re taking all these early cancers out of circulation—surgery, radiation; and so, there should be about the same number fewer late-stage cancers found. But, that didn’t happen. Mammograms catch a lot of small cancers, but with no concomitant decline in the detection of larger cancers. The more mammograms you do, the more cancer you find. But, death from breast cancer doesn’t seem to change much.

Wait a second; you just cut out tens of thousands of cancers; why aren’t there that many fewer women dying? “Together, these findings suggest widespread overdiagnosis”—meaning cancer picked up on mammogram that would have never progressed to the point of presenting during the woman’s lifetime, and so, wouldn’t even have been noticed, or caused “any harm” had it never been picked up at all.

So, if removing all these early ones didn’t lead to that many fewer late ones, that suggests that most would have never progressed during that time, or even go away on their own. That “could explain almost all [that] increase in incidence.” And indeed, “many invasive breast cancers detected by repeated mammography screening do not persist to be detected later, suggesting that the natural course of many of the [mammogram]-detected invasive breast cancers is to spontaneously regress [spontaneously disappear].”

We’ve known for more than a century that even serious metastatic breast cancer can sometimes just spontaneously go away. The problem is that you can’t tell which is which. So, if you find it, the natural inclination is to treat it, which can be especially tricky for ductal carcinoma in situ (DCIS), so-called stage zero breast cancer. “Ductal” means in the breast ducts, “carcinoma” means cancer, and “in situ” means in place, in position, not spreading outside of the duct. And, it can create these tiny calcifications that can be picked up on mammogram.

The whole point of mammograms was “to identify early invasive disease.” So, the large numbers of DCIS they found “were unexpected and unwelcome.” “Prior to the advent of [mammogram] screening,…DCIS…made up approximately 3% of breast cancers detected,” but now accounts for a significant chunk. The cells “look like invasive cancer…,and therefore the presumption was made that these lesions were the precursors of cancer” [stage zero cancer] and that early removal and treatment would reduce cancer incidence and mortality.” “However, long-term [population] studies have demonstrated that the [surgical] removal of 50,000 to 60,000 DCIS lesions annually has not been accompanied by a reduction in the incidence of invasive breast cancers. This is in contrast to [our] experience with remov[ing]…colon…polyps” with colonoscopy or precancerous cervical lesions thanks to Pap smears, “in which the removal of precursor lesions has led to a decrease in the incidence of colon and cervical cancer….” Those are cancer screening programs that work.

Radiologists argue that “overdiagnosis” isn’t so much the problem as “overtreatment.” Yeah, it sucks to get a breast cancer diagnosis, even though it would have never hurt you. But, you don’t know that at the time. So, most women undergo aggressive surgical and radiation treatment. Yeah, but if you compare the 10-year breast cancer survival for women with low-grade DCIS, among those who chose not to go to surgery at all? 1.2% of them died of breast cancer within a decade. But, in that same decade, those that went to surgery instead for a lumpectomy or a full mastectomy to cut it out—1.4% died from breast cancer. So, surgery appeared to make no difference.

That’s why there are currently randomized, controlled trials to put it to the test. But, it’s “incredibly difficult to convince a patient with…DCIS not to” just want to get it cut out. “The fear of cancer paralyzes patients,” who may resort to “drastic [excessive] measures,” like getting a double mastectomy. How can we prevent that? How about we change its name? A National Cancer Institute panel has recommended dropping the “carcinoma” part. Let’s just call it an “indolent lesion of epithelial origin”—”use language that engenders less fear.” How bad can an “IDLE” tumor be?

Another option to avoid this dilemma is just not get screened in the first place, but women aren’t typically told about any of this. Less than one in 10 women were aware that mammograms carried any potential harms at all, and more than nine out of 10 were unaware that some breast cancers never cause problems. Few were told about DCIS, but when informed about it, most wished they were told before they signed up.

Once a cancer is detected, it is currently not possible to distinguish life-threatening from potentially harmless cases. “Therefore, overdiagnosis can only be avoided by abstaining from [routine mammograms] altogether.”

To see any graphs, charts, graphics, images or studies mentioned here, please go to the Nutrition Facts podcast landing page.  There, you’ll find all the detailed information you need, plus links to all of the sources we cite for each of these topics.

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Thanks for listening to Nutrition Facts. I’m Dr. Michael Greger.

This is just an approximation of the audio content, contributed by Allyson Burnett.