Breast cancer screening: saving lives?

After my article showing that prostate cancer screening with the PSA-test does more harm than good, I was asked to follow up with an article looking at breast cancer screening with mammography. That turned out to be easier said than done, because virtually all studies of breast cancer screening only report the effect of screening on breast cancer mortality, not on overall mortality.

As I’ve discussed several times before on this blog, mortality from a specific disease is a meaningless when trying to work out if an intervention is life saving or not. The only statistic that matters is overall mortality. If an intervention decreases your risk of dying of breast cancer by 10%, but increases your risk of dying of something else by 10%, you probably wouldn’t be interested in that intervention. People care about whether they are dead or alive, not about which cause of death is listed on their death certificate.

Unfortunately, a lot of scientists don’t seem to understand this very basic concept, and so continue to produce meaningless studies showing that intervention x decreases the risk of dying of y, without any thought as to what the effect on overall mortality is.

When it comes to screening, there is a second problem, and that is that screening generates a lot of false positives. A false positive is when someone is told that they have a disease when in fact they don’t. The problem with false positives is that they lead to follow-up interventions, which can sometimes cause physical harm and even death.

In the case of prostate cancer, the initial follow-up intervention is prostate biopsy, which carries with it a risk of acute prostatitis and sepsis (which can be fatal). After the biopsy, there is a significant risk that the person with a false positive diagnosis will have surgery to remove the prostate or radiation therapy to destroy it. The problem with these interventions is that they often cause sexual impotence and urinary incontinence.

I’ve met several patients who have had their lives ruined by the treatment they received for prostate cancer. An intervention that may, or may not, have prolonged their lives.

In 2012, the Cochrane collaboration performed a systematic review to see whether breast cancer screening saves lives, and whether any benefit in terms of lives saved outweighs the human cost in terms of false positives that lead to unnecessary surgery and radiotherapy.

The systematic review identified 11 randomized controlled trials of breast cancer screening, of which three were excluded due to quality issues. Two of these were excluded because they were small trials looking at several interventions, of which breast cancer screening was just one. One study was excluded because it removed patients who died in the screening group after randomization, but didn’t do the same for patients in the control group. Obviously if you remove deaths from the screening group but don’t do the same for deaths in the control group, this will make screening look better than not screening. It is a form of scientific malpractice.

That leaves eight trials that were included in the review, with a total of over 600,000 women. The trials had slight variations in the ages at which women were included, but none looked at women under the age of 40, and most had an upper cut-off of 65 or 70, so that is the age range for which the results of these studies are applicable.

Three of the eight trials were determined to be adequately randomized, while five were determined to have a sub-optimal randomization (i.e. the randomization of participants to either the screening group or the control group was done in such a way that there was significant risk of the results becoming biased in favor of screening). Of the five with sub-optimal randomization, one was determined to be so flawed in terms of how it randomized patients, that its results were analyzed separately and not included in the main analysis. So only seven studies were actually included in the analysis.

Let’s look at the results.

First we can look at breast cancer deaths, just because that is what all the studies had as their primary end point, even though it tells us nothing about whether breast cancer screening actually saves lives overall.

When all seven studies were included in the analysis, there was a 19% reduction in the relative risk of dying of breast cancer with screening during 13 years of follow-up. The result was statistically significant. However, when only the three studies with adequate randomization were included, that decreased to a 10% relative risk reduction with screening, which was no longer statistically significant.

So, even if we look at the highly flawed metric of breast cancer deaths, we can’t actually be sure with any certainty that screening decreases them. Now let’s get to the thing that actually matters, overall deaths.

If we look just at the three adequately randomized trials, there was a 1% relative reduction in risk of dying by the 13 year mark. However, this marginal reduction was nowhere near statistically significant. In other words it was likely due to chance. Even if we look instead at the sub-optimally randomized trials with a high risk of bias, the reduction in overall mortality was still only 1% .

Just to give some perspective on what this means in terms of absolute numbers of lives saved, if we assume that the 1% reduction in overall mortality is real and not just the result of chance: Out of 318,515 women in the control group, there were 747 deaths over 13 years of follow-up. A 1% reduction in mortality would thus mean that, over thirteen years, if you screened 300,000 women, you would prevent 7 deaths. So you would need to screen over 40,000 women to save one life.

What can we conclude from this?

The highest quality evidence suggests that breast cancer screening does not save lives, or at best, has an extremely marginal effect on mortality. In which case, that extremely small potential reduction needs to be weighed against the harms caused by false positives and also against the cost of screening.

So what are the avoidable harms caused by breast cancer screening?

Apart from the anxiety induced by being told that you have breast cancer, a diagnosis generally leads to surgery and possibly also to radiotherapy. Both are potentially disfiguring, while radiotherapy can cause damage to the heart and lungs (since these organs also get hit by some of the radiation). Occasionally this results in serious complications like lung cancer, pulmonary fibrosis, coronary artery disease, and heart failure.

In the seven included studies, screening resulted in a 35% increase in the relative risk of surgery, and a 20% increase in the relative risk of radiotherapy. Both these differences were highly statistically significant. Since there was no statistically significant effect on overall mortality, we can assume that these increases represent one of two things (possibly a bit of both):

1. A lot of healthy people had surgery and radiotherapy that they didn’t need.

2. The harms caused by surgery and radiation therapy were such that, overall, people didn’t live longer than they would have without screening.

If you prevent one person dying of breast cancer but cause one person to die of lung cancer, you’ve really gained nothing. Which is why we should always only look at overall mortality, never at a specific cause of mortality.

Based on their results, the authors of the review determined that, for every woman who actually has breast cancer and has her life saved through screening, at least ten healthy women will be falsely diagnosed as having breast cancer and treated for it.

There is another aspect to consider here, and that is cost. Because screening isn’t exactly cheap. A study published in JAMA internal medicine in March of this year found that mammography screening in the US costs about 350 dollars per woman screened. Obviously the costs will vary up and down between different countries, but even if we assume a much lower cost of 100 dollars per woman screened, and that screening really does cause a 1% reduction in deaths, screening would cost four million dollars per life saved. And that is ignoring the cost of surgery and radiotherapy for the 10+ people with false positive diagnoses who receive treatment inappropriately for every true positive case that is treated. That cost also needs to be factored in.

So what can we conclude from all this?

As with prostate cancer screening through the PSA test, the probability of harm from breast cancer screening is much bigger than the probability of benefit. You are at least ten times more likely to get treatment that you don’t need than you are to get treatment that you do need. And it is highly questionable whether breast cancer screening has any beneficial effect whatsoever on mortality – if it does, the effect is tiny.

From a societal perspective, the harms are definitely bigger than the benefits, since a huge amount of money is plowed in to a highly questionable intervention, money which could instead have gone to interventions that we know save lives at a fraction of the cost.

You might also be interested in my article about scientific method in health science, or my article about whether statins save lives.

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Author: Sebastian Rushworth, M.D.

I am a practicing physician in Stockholm, Sweden. I studied medicine at Karolinska Institutet (home of the Nobel prize in medicine). My main interests are evidence based medicine, medical ethics, and medical history. Every day I get asked questions by my patients about health, diet, exercise, supplements, and medications. The purpose of this blog is to try to understand what the science says and to translate the science in to a format that non-scientists can understand.

14 thoughts on “Breast cancer screening: saving lives?”

  1. Thanks, Sebastian, another valuable enlightening piece of work. Shows that whatever threat is found has to be double or triple counter-checked and also carefully evaluated before taking any action.
    Best regards
    Franz

    1. Hi Barry,
      Thanks for the heads up. I went through the numbers and caught the mistake (at least I hope that was the mistake you were referring to!). I modified the text in light of it. It doesn’t change the overall conclusions.

  2. Thanks. Interesting article and thought provoking. How is it possible that for every 1 woman screened that actually has breast cancer, there are 10 women that receive false positives? Why is the screening so inaccurate?

    1. Hi Chris,

      It seems to be the case that many women have small cancerous growths in their breasts that will either regress on their own with time, or are so slow growing that they will never actually cause any symptoms.

      When you do mammography, it is impossible to tell if this is what you are seeing, or if you are seeing a cancer that is going to kill the patient. The same is the case when you do a biopsy – it’s often impossible to tell if what you are seeing is something that will harm the patient or not. So you err on the side of caution and treat it like cancer, and you do surgery and possibly also radiotherapy.

  3. Hi Sebastian
    Another really excellent review. Thank you and keep up the good work.
    Would love to hear your thoughts on chemotherapy for solid tumours, harms vs benefits, and use of surrogate markers like progression free survival by oncologists rather than overall mortality

  4. I think this is yet another area for investigation into big pharma corruption. I think one of the studies you mention was led by one of the co-founders of the Cochrane Collaboration Peter Gotzsche. A man of science and integrity. When he was sacked by the board, essentially for agitating for scientific integrity, some other researchers resigned in protest. He dared to question the Gardasil vaccine too so he would have been viewed as extremely dangerous by the vested interests. We can no longer leave it for a brave few, now is the time we all need to stand up for Truth.

    1. Hi Cavebear,
      I couldn’t agree more. It is unfortunate that vested interests, and the pharmaceutical companies in particular, have so much influence over medical science. I think it is one of the biggest societal problems of the time we are living in.

  5. Yes sir. And don’t get me wrong. I’m a big fan! Thanks for all of your analyses. I’m 70 now, and have been resisting baloney all of my doctors have wanted to prescribe, specifically statins. Physicals today are called “wellness visits”. Sit down and chat. Can you publish information about what blood tests, and other bodily fluid tests might be a good idea annually and would be of value in diagnosing problems early? If I have a problem I think could be helped by a doctor, I go see the doctor. Otherwise I skip the chats. Thank you!

  6. So is self-examination for a lump the only/best way to find a mass? Doctors in my HMO don’t perform breast exams anymore and haven’t for some time.

    1. Hi Loretta,
      Unfortunately the evidence on self-examination, and even on palpation by a doctor, is weak. Which is why many countries have stopped recommending that women regularly check their own breasts for lumps, and also stopped recommending that doctors palpate breasts at regular intervals. The vast majority of breast lumps are benign.

      Having said that, if you do notice something unusual about your breasts, like a lump that does not disappear within one or two menstrual cycles, or discharge from the breast, or changes in the appearance of the breast, then you should definitely go to a doctor and get it checked out.

      Also note that the review above applies to women with normal risk. If you have a heightened risk (a known BRCA mutation, or significant family history of breast cancer) the risk-to-benefit ratio is very different, and you probably should do some form of screening.

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