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Model of outcomes of screening mammography: information to support informed choices

BMJ 2005; 330 doi: https://doi.org/10.1136/bmj.38398.469479.8F (Published 21 April 2005) Cite this as: BMJ 2005;330:936

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Does screening mammography cause cancers?

 

The recent model of screening mammography by Alexandra Barratt (1) has some very interesting data. We could use their data to predict what might happen in the breast
of a woman from the age of 40 to 69 if not disturbed by the consequences of
mammographic screening. Let us wipe our slates clean and look at it
sans-prejudice
.

 

The basis of screening is to
detect cancers before they became invasive or big enough to metastasise and
kill. So in theory, the total number of cancers should remain the same in the
screened and unscreened population, but the screened women would have smaller
ones. Or, perhaps the detection of ductal carcinoma in situ (DCIS) should
increase whilst as a corollary to that, invasive cancers should reduce in
incidence, if not in the first 10 years then at least over a 30 year period.

Looking at table 2 from the
original paper (1) and concentrating on the 3 columns from the ages of 40-69.
(The numbers for unscreened population between 70-79
are not available and hence are not included.)

To estimate the natural history of
breast cancer over 30 years, one just adds up the numbers to get Table 1, in
which one can compare what happens to unscreened breasts to those subjected to
two-yearly screening mammography

Table 1

 

 

Ages 40 to
69

 

Screened

Unscreened

Interval

29

29*

Invasive

49

28

DCIS

14

1

Total

92

58

Total diagnosed- excluding interval
cancers

63

29

*The
interval cancers appear in between the two-yearly mammograms so they are in
fact symptomatic cancers. Let us assume that they are not “caused” by the
screening process itself and ignore them at present.

 

Let us now interrogate the data with two obvious questions:
Does mammography “cause” cancers? And is mammography dangerous to life?

 

Thus we start off with 28 invasive
cancers and 1 DCIS that develops among 1000
women whose breasts are not
screened over 30 years. If these breasts are subjected to mammography, then
they are found to have 49 invasive cancers and 14 DCIS, over the same period.
That is 34 extra cancers. More than doubling of risk of
diagnosis of cancer.
The unscreened women never seem to catch up with the
cancer diagnosis over 30 years, until they are 69.

 

Table 2 shows the same numbers for calculation of odds
ratios for testing alleged causality of invasive cancers, DCIS and total
cancers by mammography.

Table 2

 

 

Given Mammo-grams

Not Given Mammo-grams

Odds Ratio

95% Confidence intervals

 

No Invasive Cancer

951

972

 

 

 

Invasive cancer

49

28

1.79

(1.09 to 2.95)

p=0.015

 

 

 

 

 

 

No DCIS

986

999

 

 

 

DCIS

14

1

14.08

(1.96 to 289.75)

p=0.00076

 

 

 

 

 

 

No Cancer

937

971

 

 

 

All cancer

63

29

2.25

(1.41 to 3.62)

p=0.00029

 

 

 

 

 

 

 

 

 

 

 

 

Death

115.7

120.9

 

 

 

Remain Alive

884.3

879.1

1.05

(0.79 to 1.39)

p=0.72

 

So it appears that two-yearly mammography more than doubles
the risk of breast cancer diagnosis and increases the risk of DCIS diagnosis 14
times. Even if we include the interval cancers, the Odds ratio is 1.65 (95% CI
– 1.15 to 2.35, p=0.003). Fortunately, risk of remaining alive is not
statistically significantly altered (OR=1.05, 95% CI= 0.79-1.39, p=0.72).

 

So does mammographic screening
“cause” breast cancers? Yes, it either directly
causes cancers from ionising radiation or more likely
unearths cancers that would never surface in those 30 years if left to nature.
Is mammographic screening dangerous to life? Perhaps not,- there is no
statistically significant detrimental effect on life, suggesting that either
the cancers it induces or unearths are harmless or would have regressed anyway
(see Zahl et al above), or it detects other cancers
early enough to favourably influence their natural history, so negating the
harmful effect.

 

This unequivocal evidence from a
human experiment correlates well with 
laboratory evidence that low dose radiation such as with mammography has
a carcinogenic effect in laboratory animals and cell cultures(2).

 

The other, more plausible
hypothesis (see Zahl et al above), to explain this
phenomenon is that the extra cancers are also present in unscreened women, but
they either don’t progress or regress spontaneously. However there is some
evidence to the contrary. A study of untreated DCIS cases in the Nurses health
study (3), in which 13 DCIS cases were wrongly labelled as benign. Six of these
developed invasive cancers and 4 more were diagnosed as DCIS suggesting that
probably half of DCIS progresses
to invasive cancer. In the classic
study by David Page and colleagues(4), 28 women with
DCIS were treated with biopsy only. Eleven of these women developed invasive
carcinoma in a 30 year follow up. Applying this to the table 1, Of the 28
cancers in the unscreened group, 6 would have resulted from the 13 cases of
undetected DCIS. This gives us an estimate that 22of the 49 cancers detected by screening become
clinically apparent- a proportion similar to DCIS! (NB Many of these women
being screened and having biopsies and this may confound the issue).

 

The proportion of screen detected invasive cancers that may have
progressed to clinically evident cancers is not known. Let us now estimate how
many cancers would need to be diagnosed during screening to account for these 22
cases, for different probabilities of progression to clinical cancers. Then the
number of cancers caused by screening can be calculated by subtracting this
number from the 49 cancers that are actually detected by screening. This is
shown in Table 3

 

Table 3 shows the results of 4 possible proportions of
invasive cancers detected at screening that may progress to clinical cancers
over 30 years. Please read this table, column by column

 

Percent
of screen detected invasive cancers that we believe would have naturally
progressed to clinical cancer

45%

(similar to DCIS)

60%

80%

100%

Number of
cancers needed to be diagnosed during screening to account for the 22
cases diagnosed in the unscreened population

 

49

 

36

 

27

 

22

Number of
cancers really caused by mammographic screening per 1000 women over 30 years

 

0

 

13

 

22

 

27

 

 

So one has to either believe that more than half of invasive
cancers detected by screening would never have become clinically evident, at
least until the age of 69, (column 1 of table 3),  or, if a larger proportion (60%, 80% or
100%) of these invasive cancers progress to clinical tumours,  then screening mammography actually causes extra
cancers(13, 22 or 27, respectively), as in columns 2, 3 or 4 of Table 3.

 

Neither of these hypotheses is easily testable. Women should
be made aware that mammographic screening would double the chance of their
being diagnosed with cancer, although it is unlikely that this will adversely
affect their chance of remaining alive at the age of 69.  The relevance of this may be more sinister in
women with family history of breast cancer because tissues of women with BRCA1
or BRCA 2 gene mutations are even more sensitive to low dose of radiation (5).

 

Yours sincerely,

 

 

Jayant S Vaidya

 

 

References

 

1. Alexandra Barratt, Kirsten
Howard, Les Irwig, Glenn Salkeld,
NehmatHoussami

Model of outcomes of screening mammography: information to
support informed choices 2005;  330 (7497): 936.

 

2. Frankenberg D,
Kelnhofer K, Bar K, Frankenberg-Schwager M.

Enhanced neoplastic transformation
by mammography X rays relative to 200 kVp X rays:
indication for a strong dependence on photon energy of the RBE(M)
for various end points. Radiat Res. 2002 Jan;157(1):99-105.

 

3. Collins LC, Tamimi RM, Baer HJ,
Connolly JL, Colditz GA, Schnitt
SJ Cancer. Outcome of patients with ductal carcinoma in situ untreated after
diagnostic biopsy.

2005 May 1;103(9):1778-84.

 

4. Sanders ME, Schuyler PA, Dupont
WD, Page DL The natural history of low-grade ductal carcinoma in situ of the
breast in women treated by biopsy only revealed over 30 years of long-term
follow-up. Cancer. 2005 May 9; [Epub ahead of print]

 

5. Vaidya JS, Baum M. Benefits and risks
of screening mammography in women with BRCA1 and BRCA2 mutations.
JAMA. 1997 Jul 23-30;278(4):290

 

 

 

 

 

Competing interests:
None declared

Competing interests: The recent model of screening mammography by Alexandra

16 May 2005
Jayant S Vaidya
Senior Lecturer/ Consultant Surgeon
University of Dundee, Ninewells Hospital and Medical School, DD1 9SY