All you need to read in the other general journals
BMJ 2010; 341 doi: https://doi.org/10.1136/bmj.c5275 (Published 29 September 2010) Cite this as: BMJ 2010;341:c5275
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Dear Editor,
Gotzsche's commentary (1) to the recent BMJ short cut (2) on our
study published in NEJM (3) needs clarification. We are afraid that
Gotzsche may have misunderstood some of our results. The BMJ quotes
correctly that the 10% reduction in death from breast cancer after
introduction of the Norwegian Breast Cancer Screening Program corresponds
to a reduction of 2.4 deaths per 100,000 person-years.
The 7.2 deaths per 100,000 person-years (not 7.4 as stated by
Gotzsche), corresponding to a relative reduction of 28%, is the reduction
in the current screening group as compared to the historical screening
group. Due to the gradual implementation of the program and the
possibility to establish a current control group, we avoided confounding
by temporal changes (such as improvements in treatment and heightened
awareness) that may be associated with a reduction in death from breast
cancer. Among women in the nonscreening group, an 18% reduction in death
from breast cancer, as compared with the preceding 10-year period, was
found. This is subtracted from the 28% reduction seen in the screening
group, resulting in a 10% reduction. This 10% (95% confidence interval -4
to 24%; p=0.013) reduction is what is associated with the breast cancer
screening program.
We did not do subgroup analyses, and agree with Gotzsche, that to try
to partition the 10% reduction in breast cancer mortality associated with
the screening program would not be valuable. However, the Norwegian breast
cancer screening program consists of two components: screening mammography
and care from multidisciplinary teams. For women between the ages of 50
and 69 years, it was impossible to determine whether the reduction in
mortality resulted from earlier diagnoses associated with screening
mammography or from the management of treatment by an interdisciplinary
team.
References
1. Gotzsche PC. The Norwegian study did not find an effect of
mammography screening. BMJ 2010 Accessed at
http://www.bmj.com/content/341/bmj.c5275.full/reply#bmj_el_242918
2. Tonks A. Breast cancer saves lives, but not many. Short cuts. BMJ
2010;341:c5275
3. Kalager M, Zelen M, Langmark F, Adami HO. Effect of Screening
Mammography on Breast-Cancer Mortality in Norway. N Engl J Med
2010;363:1203-10.
Competing interests: No competing interests
Sir
Your article in Short Cuts on 2nd October, 'Subclinical hypothyroidism
linked to coronary heart disease, again' suggests that subclinical
hypothyroidism as a risk factor for coronary heart disease (CHD) has been
rediscovered. Research based on careful observation of the natural history
of CHD in families led Fowler to this conclusion 43 years ago (1,2,3).
Fowler, unlike Lykoudis who postulated a bacterial cause for peptic
ulcers many years before this was confirmed (4), is still alive to see his
research findings rediscovered and still believes that the treatment of
subclinical hypothyroidism is as important as prescribing statins to
reduce CHD incidence and mortality.
The clinical trials advocated in the JAMA article have not been
funded previously. Could this be because thyroxine, the possible
preventive treatment, is so cheap to produce that Pharmaceutical companies
are not prepared to invest in academic departments to carry out this
research?
We fear that this treatment will not be evaluated because of lack of
commercial motivation to carry out clinical trials or advertise such a
simple intervention with an already available drug. Will patients have to
wait another 40 years before their CHD can be prevented or treated?
1. PBS Fowler. Premyxoedema and coronary-artery disease.
The Lancet, 1967. Volume 289, Issue 7499, Pages 1077-1079
2. P.B.S. Fowler. Premyxoedema--a cause of preventable coronary heart
disease. Proc R Soc Med. 1977 May; 70(5): 297-299.
3. P.B.S. Fowler. Hypercholesterolaemia in boderline hypothyroidism
stage of premyxoedema. The Lancet, Volume 296, Issue 7671, Pages 488-491
4. Rigas B, Feretis C, Papavassiliou ED. John Lykoudis: an
unappreciated discoverer of the cause and treatment of peptic ulcer
disease. Lancet. 1999 Nov 6;354(9190):1634-5.
Competing interests: We are all related to Dr PBS Fowler
BMJ mentioned a recently published Norwegian study (1) under the
headline, "Breast cancer screening saves lives, but not many," and noted
that screening reduced deaths from breast cancer by 10%. Both statements
are wrong.
The Norwegian study did NOT find an effect of mammography screening,
as the 10% reduction was not statistically significant (P = 0.13). It is a
bit unusual that the authors tried to say how much of this was due to
screening per se and how much was due to other factors such as better
organisation, treatment and breast awareness. One would usually not try to
partition a non-proven effect into contributory causes. Similarly,
statisticians warn against subgroup analyses when the overall result is
not statistically significant.
It is also misleading that BMJ says that the 10% correspond to 2.4
deaths per 100,000 person years. It corresponds to 7.4 deaths, and what
the authors really reported was therefore a non-significant reduction in
breast cancer mortality of only 3% (= 10%/3) that they ascribed to
screening. This agrees with our data from Denmark (2) where we could not
see any effect of screening despite the fact that we have a much better
control group than in Norway, as only 20% of the population was screened
for a period of 17 years.
1. Kalager M, Zelen M, Langmark F, Adami HO. Effect of Screening
Mammography on Breast-Cancer Mortality in Norway. N Engl J Med
2010;363:1203-10.
2. Jorgensen KJ, Zahl PH, Gotzsche PC. Breast cancer mortality in
organised mammography screening in Denmark. A comparative study. BMJ
2010;340:c1241.
Competing interests: No competing interests
Re:Norwegian study did NOT find an effect of mammography screening
Error in my previous letter:
The last sentence in the second paragraph should read: "This 10% (95%
confidence interval -4 to 24%; p=0.13) reduction is what is associated
with the breast cancer screening program."
Competing interests: No competing interests