Now the International Prevention Research Institute, based right here in Lyon, is represented in the form of you, Philippe. Thanks for coming because you’ve been talking about organised mammographic screening programmes and, of course, the big question that you’re raising is the effectiveness of screening. First of all give me your take on this, what have you found so far? You’ve been evaluating breast and other screening, haven’t you?

Yes. We are looking at the different types of screening that are quite prevalent in our populations – cervical cancer screening, colorectal cancer screening, prostate cancer screening and breast cancer screening. Our overall conclusion at this moment is that cervical cancer screening, which is the oldest one, is very effective, that it decreases much the mortality from cervical cancer. Colorectal cancer screening is also very effective, you have a drop in the mortality from colorectal cancer, especially in those countries where colorectal cancer screening is done, being a faecal occult blood test or endoscopy, both are really effective and we see a huge difference in most countries thanks to these screening activities. But then where, say, the news are not so good is for the breast cancer because we realise now that working on that since six, seven years, the statistical data we are gathering are just showing more and more that breast screening, mammography screening specifically, is not decreasing mortality as was suggested by the randomised trials.

This has always been a difficult issue to address, hasn’t it? Because you have all sorts of confusing things like lead time bias and issues of the overall care of cancer being different. Can you tell me, what are the data? What have you done with mammography to evaluate it and what are the facts about this?

So we have done two things, basically. The first is to look at the incidence of the advanced breast cancer. Screening is a matter of diagnosing, making the detection of the breast cancer before it’s advanced. When the breast cancer is advanced it’s difficult to treat and generally it’s lethal. So all the tricks and all the purpose of mammographic screening is to catch the cancer before it’s advanced, so you catch early cancer. In fact, we have looked in cancer registries that record data on the incidence, the occurrence if you want, of advanced breast cancer in countries where there is a lot of mammography screening. In those countries the incidence of this advanced breast cancer do not drop, it does not go down. In contrast, with colorectal cancer and cervical cancer screening you have always a drop in this advanced cancer.

But there has been a big decrease of mortality from breast cancer in a number of countries and this has often been linked to mammography if only in part.

Exactly, and that’s a line of studies we have done. We have compared the mortality, breast cancer mortality, between countries that were very similar in terms of treatment of breast cancer but that had very different mammographic screening policies. For instance, you take the Netherlands where you have mammography screening since the hand of the ‘80s and we have compared the Netherlands with Belgium with a very similar population, a very similar access to treatment, but practically no screening as compared to what happens in the Netherlands. The change in mortality from breast cancer are exactly the same in the two countries. We had exactly the same between Sweden and Norway. In Norway breast cancer screening started twelve years later than in Sweden and the changes in breast cancer mortality are exactly the same in both countries. Exactly the same between Northern Ireland and the Republic of Ireland.

And the improvements in mortality you would then attribute to what?

Treatment. Two things: treatments, for sure. There have been many recent treatments and the generalisation of tamoxifen, for instance, or these hormones or the other adjuvant types of therapies are quite effective and there we have a lot of evidence that these new therapies are increasingly effective. Then there is another thing we should never forget is the fact that many countries have reorganised their healthcare service and the management of breast cancer patients nowadays is much better than twenty years ago.

Now, let me get this right, you’re saying then if you get matched pairs of countries where the approach to mammography is very different you can say almost universally that mammography has not made a difference?

Absolutely not and that has been published in the British Medical Journal last year.

So what should be done about this then?

We have to re-evaluate, I would say, what we are doing with mammography because the other problem with breast screening, especially with mammography, is the harm done by screening. We have two sorts of harmful effects, one not probably that serious, if you wish, but the false positive women are invited to screening and then they are found with a suspicious image. Because of the suspicious image on the X-ray, mammography is an X-ray of the breast, they have to go to work-up procedures, generally ending up often into a biopsy. Even if the biopsy is negative it is quite a stress for the woman.

And a stress also associated with women thinking they’re at risk and continually going to be screened anyway.

Absolutely, absolutely. So we have that stress and that stress is particularly considerable in countries where you have a lot of screening. For instance, you take the champions, world champions, the United States, in the United States we know that women starting screening at 40 years of age, every year until they are aged 65 or 69, there is practically a 50% chance to be once to have a biopsy. You can imagine that, it’s quite tremendous. Then there is a more serious type of harm is the over-diagnosis, that mammography is detecting a number of small cancers generally but that are indolent. We know that these cancers will never progress into invasive, dangerous cancers. These are pussy cats, as we say in our jargon. These pussy cats, in fact they could just have been left there and they would never become life-threatening. Over-diagnosis also concerns another type of very strange cancer that’s called the in situ breast cancer. Before mammography screening in situ breast cancer… in situ are cancers that are confined, say, to the area where they are, they do not invade the surrounding tissue, they are just looking to just stay where they are. Under the microscope, again, it looks like being a cancer.

And there are lots of those, aren’t there?

Of course, there are lots. And before mammography screening you had barely no more than 2% of all breast cancers were in situ. Since mammography screening is done from 10-20% of breast cancers are in situ.

And there’s a lot of discussion about whether you should aggressively treat them.

Of course, nobody knows exactly what to do with these in situ cancers. We know that having a woman with in situ cancer does have a higher risk, a greater risk, of developing a breast cancer in the future but we don’t know whether the number of women that are going to have a breast cancer, an invasive breast cancer, after an in situ, it’s a small amount.

Now we’re talking specifically about mammography here. What about the high risk patients, those with a genetic or family history? Is mammography justified there? There are other modalities.

Of course. Generally mammography is done in those women but it’s supplemented by other imaging modalities and the most frequent one being magnetic resonance, MRI.

So would you kick mammography into the long grass then, completely?

I think we should certainly think very rapidly of something else, in changing mammography into something else.

And women who are anxious about their breasts, what should they do? Breast self-examination again?

In fact, two things that really have some importance and recognition is awareness, first of all. Breast awareness is something very important.

Are women well informed?

They should be much better informed…

Than they are.

They are much better informed nowadays than twenty years ago. Twenty years ago breast cancer was a hidden problem, I would say, and nowadays it’s all over the place, you see it in all the newspapers and so on. Where there is a problem with information is information about the mammography screening because women think that thanks to mammography screening they can avoid sometimes to have a breast cancer when in fact mammography screening is meant to prevent mortality from breast cancer. So in fact women do not realise that when attending mammography screening the risk of breast cancer is in fact greater than if they were not attending mammography screening and that’s the real truth and women do not know that, they do not realise that problem.

Because of the radiation?

Not because of the radiation, essentially, because of the over-diagnosis, those small tumours, these in situ tumours. So many women…

The risk of cancers which would not have been serious, yes.

Absolutely, not be serious.

I know here at the meeting in Lyon you’ve been talking about mammography but I can’t resist asking you very, very briefly to talk about prostate cancer. What’s the situation there, very briefly?

Prostate cancer is the PSA testing, the prostate specific antigen testing is now recognised a harmful type of screening. So the harm due to PSA screening really outweighs the possible benefit you could have. First of all the benefit is very hard to measure. The randomised trials that have been done with PSA testing, they all came with different conclusions so it’s difficult to assess but there is a lot of evidence that you have a lot of harmful effects due to screening, essentially because you detect a number of small indolent prostate cancers that will never, never be life threatening.

And what about digital examination?

Digital examination, that’s a very clinical exam. Generally it’s considered that when your prostate cancer you can feel it, the urologist can feel it with a finger, generally it’s probably already too late, it’s a problem.

So what’s your advice, then, about prostate cancer and about mammography, how to deal with these situations internationally in the countries that have taken them very seriously and the countries which might take them more seriously.

So let’s start with prostate cancer, it’s the easiest one. I would say that there should be a ban on PSA screening, that for sure. Prostate specific antigen is meant for the follow-up of men that are diagnosed with the prostate cancer and then you want to follow, the clinicians want to follow, to see whether the management of these patients is right or not. That’s the purpose. It was not meant to be a screening tool and that screening tool should no longer be used for screening, that’s the first thing. Then when it goes to mammography we should certainly change the current approach with mammography and certainly put the emphasis on research for other imaging techniques and also biomarkers and just avoid believing that the mammography is doing any good to women.

So if you spent that money on other imaging techniques and biomarkers what kind of benefit do you think could ensue?

Probably it would take certainly a number of years because we have to test it, of course, so it would take a number of years but the first thing is to identify those women that are more likely to develop a dangerous breast cancer. The issue nowadays is no longer to detect those women who are going to have a breast cancer, it’s those who are going to develop a dangerous breast cancer.

And we are talking about a lot of money, the money spent on mammography could fund a lot of research.

Yes, because the curious effect in science here is that relatively little money has been spent for the trials on mammography screening. I would say it has been a few tens of millions, if you want, whereas what is spent nowadays for doing mammography screening, it’s a considerable amount of money. These are hundreds of millions of euros, dollars, whatever. So in fact you would just divert 5-6% of all that money for new research, it would really be a good thing.

And what’s the take-home message here from your presentation in Lyon to healthcare planners?

Healthcare planners, they should think twice now before extending anything with mammography and if they can prevent implementing mammography in areas where mammography is not yet in place, they prefer to wait that something much better for higher efficiency would come and would be available before doing so. Now, where you have already mammography being done, please have good information for women so that women can make an informed choice as to whether going or not going to mammography. So to give them a fair account of the benefits that are small but also of the side effects that are substantial so women can make their decision. Present all the leaflets that are given as information, with that women first of all think wrong things like mammography can prevent breast cancer, which is totally false, it increases the risk of breast cancer. And they also over-estimate the benefit they could have. In that respect the information to women must come back to something that is in phase, that correlates really with what we know and what we don’t know about the efficiency of mammography screening.

Philippe, thank you very much.

You’re welcome.