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Vinay Prasad @VinayPrasadMD
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TIme for TWEETORIAL PART 2 on mammographic screening.
A MULTI-part series on this topic

Today, we we will review this 2012 paper by
Archie Bleyer, a fellow OHSU faculty member, and.... H. Gilbert Welch

Sit down, It's a doozy.
Quick recap: In Part 1, we covered this provocative paper by Juni & Zwalen in the @AnnalsofIM on the randomized data for mammography.

Here we take a CLOSE LOOK at what mammography screening has brought us over the last 30 years in the USA
Bleyer and Welch begin their paper with a clear, and indisputable insight
In order for mammograms to deliver benefit, they must
1. Find more early cancers (confined to breast)
2. Leading to fewer advanced cancers (in the lymph-nodes or distant organs) among women over time
Does that make sense?
For screening to work: you gotta detect cancers that would otherwise spread, before they do. By acting upon them (surgery, radiation, chemo) you have to keep them from spreading-- that's the theory
Early goes up
Distant goes down
Make sense?
The first thing they do is document that, over time, more and more women over 40 have indeed had mammographic screening, shown here.
Nothing controversial here.
Clear and steady uptake.
Next they plot the rise in mammographic screening, alongside the detection of early stage cancers per 100,000 women

It rose from 112 to 234. Quite a jump!
But that makes sense, right?
More mammograms means more detection of early breast cancer.
That is how it is supposed to work.
What should then happen is for distant/ advanced/ late stage cancers to...
The answer is fall, and ideally proportionately to the rise in early cancers. Of course, distant/late cancer may not fall right away, perhaps after a lag-- corresponding to the time it would have taken them to spread.

But instead of noting a fall, Bleyer and Welch found this
What word comes to mind....
It's not exactly reassuring.

The massive rise in the detection of early breast cancer did not result in a commensurate decrease in advanced/ late cancers, in fact, late cancers have barely budged. (102 per 100k to 94)
If you look even closer, you will see that is explained entirely by a reduction in loco-regional (node +) cancers, but not distant cancers.
Why does this matter?
Well, the goal of this entire thing is to catch and treat cancer before it spreads to distant sites, and to treat it SO IT DOESN"T SPREAD.
But Bleyer and Welch find no evidence that this has happened.
They also make this good point:
Right now you might be racking your brain for other explanations.
What if 2 trends are occurring that cancel each other out?
What if more cancer occurs for biology reasons, & screening is keeping it at bay?
Without mammograms, distant cancer would rise, you may contend
Bleyer and Welch thought of that, and looked at the trends in cancer for women YOUNGER than 40 (a group that was not extolled to undergo screening)

They find no evidence for the canceling trends theory.
It is hard to say dispassionately what Bleyer and Welch are showing.

They are suggesting that decades of mammographic screening has resulted in MANY MANY women given the cancer label, subjected to a battery of invasive interventions, which did not benefit them.
The word researchers use to describe these cancer labels is overdiagnosis-- being given a cancer diagnosis or label when, had the screening test not been performed, that label would NOT have been given in the woman's life
In the last part of the paper, Bleyer and Welch try to estimate how many American women may have been overdiagnosed over the last 30 years.

Like much of the work I do (estimating things people don't want estimated), they use CONSERVATIVE assumptions
Conservative assumptions here means, if anything, underestimate.
(when we estimated use of cancer molecular therapy we used assumptions that likely overestimate it)

Scientists use conservative assumptions to move people from the position they are entrenched in closer to truth
But not too fast as to make their heads explode.

Anyway Bleyer and Welch sliced it, over 1,000,000 women had been over-diagnosed.

At least 50k per year.
How can this be reconciled with the simple fact the death rate from breast cancer has dropped over this time?

This is what the conclusion they authors reach:
The author end with one of the most poignant paragraphs in the medical literature, a sober reflection on something the profession not only endorsed, but extolled;
Not just offered, but persuaded, badgered and pushed.
More parts to come on this topic, as promised, and all are with the goal to move past the insipid debate, and simply educate.

There are many classic papers that proponents cannot read because of the anger they feel.

That's the anger inherent in questioning the status quo.
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