Download Daniel B. Kopans, M.D. Professor of Radiology Harvard Medical

Daniel B. Kopans, M.D.
Professor of Radiology Harvard Medical School
Senior Radiologist Breast Imaging Division Massachusetts General Hospital
A Review of and Response to:
Overdiagnosis Of Invasive Breast Cancer Due To Mammography Screening: Results
From The Norwegian Screening Program. Kalager M, Adami HO, Brettauer M, Tamimi
RM. Ann Intern Med 2012;156:491-499.
Mammography screening is one of the major medical advances of the past 50 years.
The death rate from breast cancer was unchanged for 50 years until mammography
screening began in the mid 1980's in the United States. As expected, 5-7 years later
the death rate began to fall, and, as more and more women participated in screening,
the death rate continued to fall so that it has decreased by over 30% since 1990. This
means that there are 30% fewer women who die of breast cancer each year than would
have died had the death rate been unaffected. Therapies have improved, but it is clear
that therapy saves lives when breast cancers are found earlier.
Despite this major advance, efforts have persisted for 40 years to try to limit access for
women to screening. It was argued that we could not possibly screen all women in the
U.S. This was shown to be false. It was suggested that mammography screening led
to too many biopsies with benign results until it was shown that biopsies for actual
lumps in the breast are even less likely to be cancer, and when they are cancer they are
less likely to be cured then those found by mammography screening. It was suggested
that mammography compression could squeeze cancer cells into the blood leading to
earlier deaths - a ridiculous idea that was shown to be preposterous. It was suggested
that there was a sudden jump in the detection rate of cancer at the age of 50. This was
shown to be false. Arguments have been presented and refuted that screening does
not benefit women until the age of 50. It was suggested and refuted that there was no
benefit from screening for women at any age. This was also shown to be scientifically
false.
The list goes on and on. Deceptive analyses are refuted scientifically, only to be
replaced by a new "analysis", or a recycled old one that is promulgated in an effort to
reduce access to screening.
Kalager published a paper suggesting that the decrease in breast cancer deaths in
Norway was predominantly due to multidisciplinary care with very little due to screening.
Inexplicably that determination was made with only 2.2 years of follow-up when it is
clear that the benefits of periodic screening would not be expected for at least 5 years.
It is difficult to determine exactly what the authors have done in this most recent paper.
It is clear that the peer reviewers likely gave up and just decided that they liked the
conclusions without really understanding the methodology. It is interesting that the
authors quote the other opponents of screening, led by the so called "Nordic Cochrane
Center", at lest 16 times. These others have suggested that 30-50% of cancers found
by mammography would "melt away" if left undetected. However Kalager et al write
"Our estimates of overdiagnosis are lower than previously reported from Norway, where
the percentage of overdiagnosis of invasive breast cancer was estimated to be 37% (2
Jorgensen and Gotzsche) and 54 % (3 Zahl et al), based on different approaches to
account for temporal trends and lead time."
This pretty much says it all. These studies are all attempts to "adjust" for factors that
cannot be controlled. They are estimates rather than direct measurements. It is
interesting that, as these analysts "refine" their estimates, the claimed amount of
"overdiagnosis" decreases for the same population being studied. The next analysis
will likely find even less "overdiagnosis".
This is all smoke and mirrors. Figure 2 in the paper tells the story. These and the other
authors have looked at the "incidence" of breast cancer (it is really the cancer detection
rate) before women were offered screening and the incidence after screening was
instituted. The authors would argue, correctly, that when screening starts, there is a
jump in the cancers detected which is clearly evident in 1996. This is the "prevalence"
screen where cancers that have been building up undiagnosed are added to the
cancers that would have been diagnosed in 1996 and these are all added to the
cancers that are detected by screening 1, 2, 3, etc. years earlier due to mammography
screening. The question is, once the screening program has begun, should we expect
that the curve will return to the same incidence as before screening began? In other
words, shouldn't cancers be reaching the new detection threshold at the same rate as
before, but found at a smaller size? Superficially this would seem to be correct. Their
argument, and the argument of others cited by this paper is, essentially, that since the
curve does not return to the same prescreening rate, the difference between the new
detection rate and the prescreening detection rate must be due to cancers that are
being overdiagnosed by screening.
What they have claimed to have taken into account (but it is unclear that they have
done so) is the fact that earlier detection (leadtime) means, for example, that women
age 50 will now have the cancer detection rate of women age 52 (if mammography finds
cancers 2 years earlier). Women age 52 have more cancers each year than 50 year
olds, etc. The incidence curve is shifted to the left meaning that the cancers detected
would stay elevated above the prescreening level due to leadtime. They also did not
account for the fact that new women enter the screening program each year. These,
previously unscreened women, bring with them new "prevalence" cancers and a
commensurate "mini bump" in incidence each year, and this also prevents the curve
from returning to baseline. Finally, the question is - what is the baseline incidence that
would have occurred in the absence of any screening and toward which the new
incidence curve is expected to return ? Figure 2 shows that the incidence in
unscreened women increased over the period studied. It would appear that it was
increasing even faster before the start of screening among the women who were going
to participate in screening. Both methods of estimating what the incidence would have
been had screening not been initiated show that the baseline was increasing so that the
distance of the screening groups above their extrapolated baseline was even less than
above the so called nonscreening group's baseline.
In summary, even using this, methodologically questionable approach, the difference
between the actual cancer detection rate and the expected is less than the authors have
concluded, and almost all the difference is explained by leadtime, new prevalence
cancers, and an increasing baseline. The rate of "overdiagnosis" is much lower than
that suggested by the authors. In fact, as the authors acknowledge, the only way to
really measure "overdiagnosis" is with a randomized, controlled trial. What they
neglected to point out is that there have been two such analyses. One showed that
overdiagnosis is actually less than 10% while the other showed it was less than 1%.
The conclusions of the Kalager paper are, simply, incorrect.
Unfortunately, there has been a renewed effort, spearheaded by the so called "Nordic
Cochrane Center", to try to deny women access to screening. As noted earlier, similar
efforts have been shown to be scientifically unsupportable so that those with this
agenda have now turned to the specious arguments of overdiagnosis and
overtreatment. If as many as 50% of cancers found by mammography would "melt
away", why have there not been multiple series published documenting such cancers
disappearing without therapy?
In the Harvard teaching hospitals 75% of women who die from breast cancer are among
the 25% of women who do not participate in screening. One could, cynically, suggest
that the best way to reduce "overtreatment" would be to stop treating women unless
their cancers are detected by screening since the vast majority of the women with
breast cancers who do not avail themselves of screening will account for most of the
women who will die (clearly not being saved by treatment). This is, of course, absurd.
It is time for the nonsense to stop. Peer review has clearly broken down. The general
medical journals have a responsibility to provide, scientifically, legitimate research
without bias so that the public can make informed decisions. Mammography screening
is not the ultimate answer to the breast cancer problem, but these repeated efforts to
end screening will result in large numbers of, unnecessary, deaths.