Results
Reducing mortality was defined as the most important goal of a mammography screening
programme. Besides this main effect, there are other positive effects that result
from an earlier detection of cancer. They relate above all to less invasive
treatment options (more breast retention, avoidance of axillary dissection,
reduction in chemotherapy and a better cosmetic result).
The fact that interval carcinomas and also advanced stages are not preventable
indicates the limits of mammography screening.
Potential side effects result from the low dose of radiation applied, from
false-positive diagnoses, and possible overdiagnoses.
Reduction in mortality
The reduction in mortality through mammography screening was investigated in 8
randomised studies. These showed that a reduction in mortality of approximately
30 % is to be expected on average for a woman taking part every 2 years over a
period of 20 years.
Since the year 2000, the results of the randomised studies have been called into
question by Goetzsche. He initially attempted to declare 6/8 randomised studies
as invalid due to the cluster randomisation (a common and recognised
randomisation technique) used in these because, in principle, age differences
can occur between study and control groups when cluster randomisation
(invitation/non-invitation to entire locations/cities) is used [4]. He therefore excluded 6 out of 8 randomised studies
based on his own formalistic definition, although it was possible to show that
the, in some cases opposing, average age differences between the studies (of
just a few months in each case) had no effect on the overall result.
Of the remaining 2 studies, which Goetzsche continues to this day to assess as
reliable according to his own definition, the study conducted in Canada is
highly controversial due to significant deficiencies in mammography quality and
due to possible severe flaws in randomisation [5], [6], [7].
During the study conducted in Malmö, the verifiable effect was reduced as there
was a high cross-over level (high proportion of participants among the uninvited
women and vice versa).
In further publications, Goetzsche [8] doubted the
objectivity of the manner in which cause of death was determined in some of the
studies. These claims have not been confirmed following re-evaluation of these
studies by an independent WHO commission [9].
Despite the clear statement by the WHO in 2002, Goetzsche continues to insist on
a selectively different assessment of the present randomised studies and also
postulates a mortality reduction of just 15 % between invited vs. uninvited
women.
In 2012, an independent panel of experts in the United Kingdom was commissioned
to re-evaluate the mortality reduction [2]. The
independent panel re-evaluated both the data from the randomised studies and the
available meta-analyses and took into account arguments from screening advocates
and opponents. It was clear that a mortality reduction of 20 % can be assumed
with regard to invited vs. uninvited women. As in the randomised studies only
70 % of the invited women took part in the screened group, a mortality reduction
of 20 % relating to invited vs. uninvited women corresponds approximately to a
mortality reduction of > 30 % for actual participants [10]. Overall, the independent British expert commission thus confirms
the results of the randomised studies and the statement by the WHO from
2002.
The British expert commission explicitly confirms that it can find no reason to
exclude some of the randomised studies. It also takes the view that the effects
of improved treatment and effects of diagnosis are very likely independent of
each other, so the proven mortality reduction achieved through mammography
screening is to be expected in addition to the treatment improvements made
since. Reference is also made to the simultaneous improvement in mammography
technology since the randomised studies were concluded (30 years ago).
Naturally, no further randomised studies have been possible since state screening
programmes were introduced. This means that other study types are required in
order to be able to assess the effect among participants vs. non-participants.
Institutions which supervise the screening programmes in the screening countries
and have assessed the primary data have explicitly indicated the need for a
correct statistical methodology [11].
Simple trend analyses are considered unsuitable as cases of breast cancer that
already occurred prior to the start of the screening programme and the deaths
resulting from these cannot be correctly separated out. This can lead to
significant underestimates of mortality reduction. Furthermore, additional
external influences cannot be sufficiently identified or taken into account.
Incidence-based mortality studies and case-control studies appear suitable [11], [12]; however, an
under- and overestimate of the effect is possible both for mortality studies and
case-control studies. An adequate follow-up period is of the utmost importance.
As breast cancer was discovered many years earlier in some cases in the study
group, it is essential for calculating mortality reduction that the tumours
discovered significantly later in some cases in the control group and and their
later follow-up are recorded. If one takes into account that tumours become
symptomatic following a period of time that differs greatly from individual to
individual (example DCIS), but can then progress in very different ways, a
follow-up period of at least 10 years is considered indispensable.
Additional possible influencing factors are also to be taken into account for all
the study types. These relate to regional differences, time-based trends,
relevant age differences, and the influence of diet and medication that can
occur between the study group and the selected control groups.
A systematic review, which analysed studies from 18 screening countries with
regard to the correct statistical methodology and included those studies that
fulfilled the aforementioned requirements, showed an average mortality reduction
for actual participants of 43 % (38–48 %) using the data from 18 screening
countries [13].
Studies that recently reported an incomprehensibly low mortality reduction [14], [15] indicated the
aforementioned problems, e.g. no segregation of the carcinomas that occurred
prior to screening, as well as, in the final case, a follow-up period of just 2
years (!).
Data on mortality reduction are to be expected from the German programme at the
earliest 10 years after the national screening programme is established
nationwide. The necessary data protection regulations are currently still being
finalised for this purpose across the country.
The process and results parameters available to date that influence mortality
(detection rates, stage distribution of the discovered carcinomas) enable an
effect comparable with that of other programmes to be expected for Germany.
[Tables 1] and [2]
show the most important results obtained in the years 2008–2009 and the
requirements in accordance with EU Guidelines. [Fig. 1] offers an overview of the stage distribution of the
carcinomas discovered in the screening programme compared with the stage
distribution within the same age groups before the screening programme started.
[Fig. 2] shows the carcinomas that do not involve
the lymph nodes in the target population and among the screening
participants.
Fig. 1 Simple T-stage distribution of invasive breast cancers in the
screening (2005–2007, 2008–2009) and in the target population (2000–2005).
There is a noticeable increase in small invasive carcinomas in the screened
population [24].
Fig. 2 Proportion of lymph node-negative carcinomas in the screening
(2005–2007, 2008–2009) and in the target population (2000–2005). The effect
of the screening can already be seen at the beginning of the programme: an
increase in node-negative carcinomas with a simultaneous reduction in
node-positive carcinomas in the screened women [24].
Table 1 Most important results: Performance parameters
with regard to the detection of breast cancer. Performance
parameters affecting the detection of breast cancer: all parameters
correspond to the requirements of the EU Guidelines [1], [24].
|
Parameter
|
Reference range EU Guidelines, 4th edition
|
Results screening Germany 2008–2009
|
|
|
First examinations
|
Subsequent examinations
|
First examinations
|
Subsequent examinations
|
|
4.
|
Breast cancer detection rate (multiple of the regional
background incidence)
|
≥ 3 × IR
|
≥ 1.5 × IR
|
Regionally fluctuating (1.7–4.6)
|
Regionally fluctuating (1.4–4.0)
|
|
5.
|
Breast cancer detection rate (cases per 1 000)
|
approx. 7.5/1 000
|
approx. 3.8/1 000
|
8.2 ‰
|
5.6 ‰
|
|
6.
|
Proportion of in-situ carcinomas
|
10 %
> 15 %
|
10 %
> 15 %
|
19.5 %
|
19.8 %
|
|
7.
|
Proportion of invasive carcinomas ≤ 10 mm
|
n. a.
≥ 25 %
|
25 %
≥ 30 %
|
30.0 %
|
34.9 %
|
|
8.
|
Proportion of invasive carcinomas < 15 mm
|
≥ 50 %
|
≥ 50 %
|
51.3 %
|
57.2 %
|
|
9.
|
Proportion of carcinomas not involving the lymph nodes
(N−)
|
n. a.
> 70 %
|
≥ 75 %
|
74.8 %
|
79.0 %
|
|
10.
|
Proportion of carcinomas in UICC stage II+
|
n. a.
< 30 %
|
≤ 25 %
|
28.9 %
|
24.2 %
|
Table 2 Most important results: Performance parameters
with regard to investigation. All performance parameters affecting
investigation fulfil the requirements of the EU Guidelines 4th
edition [1], [24].
|
Parameter
|
Reference range EU Guidelines, 4th edition
|
Results screening Germany 2008–2009
|
|
|
First examinations
|
Subsequent examinations
|
First examinations
|
Subsequent examinations
|
|
3.
|
Call-back rate
|
5–7 %
|
3–5 %
|
6.1 %
|
3.0 %
|
|
11.
|
Proportion of preoperatively detected carcinomas
|
≥ 90 % (3rd ed. > 70 %)
|
91.7 %
|
|
12.
|
PPV I
|
n. a.
|
14.8 %
|
|
13.
|
PPV II
|
n. a.
|
49.4 %
|
Less invasive treatment
If one combines the more favourable stage distribution of the carcinomas among
screening participants with the current approach in line with the guidelines, it
is clear that benefits of early detection in no way only apply to women whose
lives can be saved. Naturally, better cosmetic results, a higher rate of
breast-conserving therapy (BCT), fewer axillary dissections and less
chemotherapy are to be expected when smaller carcinomas are discovered.
Screening opponents also report here on a lack of benefits or even of
disadvantages (e.g. higher mastectomy rates) [8], [16].
The reported disadvantages relate in one case to very old data (prior to
systematic introduction of BCT) [8], in another case
[16], these calculations may have arisen from a
counteracting effect caused by the simultaneous introduction of screening and a
parallel change in therapeutic standards (modern treatments particularly
benefitted the carcinomas discovered later in the control group).
Contrary to the calculations by screening opponents, responsible institutions in
various countries were able to demonstrate the following benefits (to be
expected from the changed stage distribution) for screening participants:
-
A reduction in mastectomies in favour of a higher BCT rate
-
A higher rate of sentinel lymph node operations with a reduction in
axillary dissections [17], [18], [19]
There is still the absence of a Cancer Register comparison in Germany, but an
incidence-based trend analysis from Bavaria is now available for the first time.
This compares treatment trends from 2000 to 2008 for various age groups. These
show the following initial trends for the age group of 50- to 69-year-olds (at
participation in screening, which rose during this period from 0 to approx.
30 %) in comparison with the other age groups: mastectomy rates falling more
significantly, more pronounced fall in adjuvant chemotherapies, more pronounced
fall in axillary dissections [20].
Radiation dose
As radiation can trigger cancer, it is particularly important that the radiation
dose is optimised for screening, where predominantly healthy women are regularly
examined with X-rays. However, the image quality and dose are closely linked. In
order to achieve optimal image quality with a minimal required dose and thus
ensure that the smallest changes are detected, apart from using modern
technology, optimally coordinated equipment, parameters and positioning, the
continuous training and testing of diagnosticians, and the optimisation of the
entire screening chain are crucial. The most important technical components are
monitored daily online and annually in person during the screening. According to
early cancer detection guidelines and German X-ray regulations, what are known
as IGeL mammograms (individual healthcare services not featured on the list of
services covered by statutory health insurance companies), for which all the
provided quality assurance for the screening can be circumvented, are not
permissible for early detection in asymptomatic women.
A mean parenchyma dose of significantly below 4 mGy is now assumed within the
quality assurance provided for the screening. (The parenchyma dose required on
an individual basis varies considerably depending on breast size and
compression.)
Overall, (according to current calculations) the risk of triggering breast cancer
through a mammogram is very clearly (factor of 50–100) below the annual natural
risk of suffering from breast cancer as early as from the 40th year of life
[21], [22]. If one
assumes that mortality can be reduced through quality-assured mammography
screening, which naturally also applies to rare cases of triggering cancer
through mammography, the calculated benefit is significantly greater than the
risk. This is the reason why mammography screening is approved and recommended
in Western countries. According to the S3 Guidelines [23], the radiation dose applied during a screening mammogram cannot
be considered an argument against screening mammography.
False-positive rate
The German Mammography Screening Programme is conducted purely in the form of
mammography screening according to EU Guidelines. If an abnormality is detected
as part of independent double reading and the subsequent consensus conference,
the doctor responsible for the programme (DRP) invites the woman for further
tests (called an imaging assessment). During most imaging assessments,
malignancy can be excluded from the very first diagnosis appointment. If this is
not possible, a histological assessment follows, which is carried out by highly
experienced examiners as gently as possible using minimally invasive methods in
over 90 % of cases. When assessing the programme, every invitation for
investigation counts as a positive finding and is designated as “false-positive”
if the finding is ultimately discovered to be benign. The investigations
conducted in Germany are already being collected prospectively and are thus
clear [24]. For the years 2008–2009 ([Tables 1] and [2]), 6.1 %
of women were invited for further investigation at the first examinations, which
corresponds to a “false-positive rate” of 5.3 % with 8.2 carcinomas discovered
among 1000 screened women. At subsequent examinations (women who take part in
screening repeatedly) an average of 3 % of women were invited for diagnosis with
5.6/1000 discovered carcinomas, corresponding to a “false-positive rate” of
2.44 %.
Histological assessments (usually minimally invasive investigations) were
conducted in the screening in 2008–2009 for 1.5 % of all women (first and
subsequent examinations)[1] whereby a malignant
tumour was found in 7.6/1000 women[1]. This
corresponds to a rate of 0.74 % false-positive biopsy recommendations.
Screening opponents calculate the number of “false-positive findings” over 20
years of screening based on far higher investigation rates in the USA and talk
of so-called “false-positive rates” of up to 50 % in the screening. This does
not apply to the German programme.
In addition to the rate of false-positive biopsy recommendations, the
false-positive rate (relating to the recommendation for further investigation)
in the Mammography screening is far lower than for other imaging methods, at
5.3 % in the first and 2.44 % in the subsequent screening cycles [25].
If one then calculates false-positive rates relating to the 20-year “screening
life” of a woman in the German Mammography screening, this indicates, using the
results gathered prospectively for 2008–2009 [24],
that < 300 out of 1000 women on average would be invited for additional
imaging once within 20 years due to an ultimately benign finding. A histological
assessment is required to determine a benign finding in 74 of these women on
average. At the same time, 76 breast cancers are found in the screening during
this period.
In comparison with the pooled results from other screening countries [26], the call-back rate for imaging investigations in
Germany is somewhat higher on average, with a comparable rate of histological
examinations. Of particularly favourable note is the considerably lower
proportion of open biopsies, which is explained by the consistent introduction
of modern minimally invasive techniques in the German programme.
Interval carcinomas
Interval carcinomas are defined as carcinomas that occur within 24 months
following a screening mammogram without pathological findings (i.e. in the
screening interval). They are not to be equated with overlooked findings, as
these only constitute a proportion of interval carcinomas (see below) [29]. However, they indicate the limits of a screening
programme.
Breast cancers can develop at any time (and not just every 2 years); the
screening measures only take place at set intervals (every 2 years). There are
no methods (either mammography or other imaging procedures) that have a 100 %
prediction probability for 2 years, meaning that interval carcinomas are
unavoidable throughout the world and with the use of all screening methods.
Interval carcinomas in mammography screening are comprised as follows:
-
Carcinomas that develop in the interval and thus did not exist (“no
sign”) at the time of screening.
-
Carcinomas that exist at the time of screening but are not identifiable
(“no sign”) using the Mammography method (even retrospectively).
-
Carcinomas that are prospectively not identifiable or cannot be
differentiated from benign changes with sufficient certainty, but their
existence or development in a corresponding location can be suggested
retrospectively based on an unspecific mammographic change (“minimal
sign”).
-
Carcinomas that are overlooked or incorrectly assessed (even by 2
experienced examiners with independent readings) (“missed” or
“misinterpreted”).
A distinction between the aforementioned groups is in no way trivial, as there
are naturally blurred transitions. As mammography is difficult to interpret
(like other mamma-diagnostic methods) due to the countless standard variants and
various benign changes, widely different assessments can be made in some cases –
depending on the prior information (knowledge of location and appearance of the
carcinoma subsequently diagnosed vs. blind diagnosis mixed with unremarkable
cases) [26]. Where there is a lack of blinding and a
retrospective assessment, the prospective diagnosability of a finding can
sometimes be significantly overestimated, particularly by less experienced
assessors when the localisation of a finding is known to them.
For patients and investigators from outside this field, it is also sometimes
difficult to understand that, although mammography generally offers good
sensitivity for small carcinomas, it is sometimes not possible to diagnose
larger carcinomas using mammography. This is explained by the fact that,
depending on the mammary glands and carcinoma type, carcinomas that do not
contain any micro-calcifications can be hidden by denser glandular tissue or
benign changes, or imitate these changes. This can particularly apply to
diffusely growing carcinomas and carcinomas that develop in pre-existing
asymmetries (which frequently occur as normal findings).
Overall, based on the results of European screening programmes, one assumes that
approx. 25 % of all carcinomas that occur or develop among screening
participants within 2 years are diagnosed in the interval [1], [27]. Carcinomas that are actually
overlooked may only constitute a small proportion of all interval carcinomas
(below 5–10 %) with independent double reading in this regard.
No precise figures are yet available for the German Mammography Screening
Programme due to the data protection regulations still undergoing
clarification.
An initial fully anonymised Cancer Register comparison for the years 2005–2007
(first screening cycle) from North Rhine-Westphalia [28] indicated a proportion of 22 % interval carcinomas. This
corresponds to a mammography sensitivity of 78 % for the first cycle based on
the whole (!) 2-year interval. For a woman with an unremarkable screening
finding, the probability that no breast cancer will also be found in the
interval during the following 2 years is at > 98.8 % (negative prediction
value).
In other words, one could also say that an interval carcinoma must be expected in
15 out of 1000 women with unremarkable mammography screening findings (first
cycle).
Due to the anonymisation currently required under data protection law, it was
still not possible to conduct analyses of individual cases. Owing to the
naturally lower breast cancer detection rate in the subsequent screening cycles,
a somewhat lower overall sensitivity is to be expected for future calculations.
Programme sensitivities between 67 and 84 % are reported from established
European screening programmes [27].
These results, like (see above) the other surrogate parameters, are indicative of
the good quality of the German Mammography Screening Programme by international
comparison. This result also includes the possibilities of errors (counteracting
in each case), as there is no individual case comparison and there are remaining
gaps in the Cancer Register.
Overdiagnoses
Overdiagnosis is defined as the diagnosis of breast cancer which would not have
been discovered during the womanʼs lifetime without screening. Overdiagnoses are
thus unwanted screening results. In the biological sense, additionally diagnosed
breast cancer in the screening group is just as much real breast cancer as any
breast cancer discovered outside of the Screening Programme, the early detection
of which can save lives.
Overdiagnoses are created in that breast cancer is sometimes identified much
earlier in the screened group than in the unscreened group (called lead-time
bias). This early diagnosis then becomes overdiagnosis when the breast cancer,
for instance in the case of a low-grade DCIS, develops so slowly that the
patient dies before the breast cancer would have become symptomatic (without
screening).
As neither the remaining lifetime of the woman nor the precise course of the
illness without discovery can be predicted on an individual basis, overdiagnoses
can never be determined in an individual woman with certainty.
The calculation of overdiagnoses and how they differ from early diagnoses is
extremely difficult and subject to considerable uncertainties, as assumptions
are always required here. Assumptions are always required for such calculations.
Depending on the calculation method, there are extreme deviations in the
calculation of expected overdiagnoses. Estimates of between 0 and 50 % of all
breast cancers diagnosed in the screening have been published [30], [31], [32], [33], [34].
The possibilities of errors may be present for all estimation procedures [11], [30], [35].
Calculations of extremely high overdiagnoses [31], [32] can largely be explained
methodologically, e.g. through an inadequate follow-up period, insufficient
consideration of the length-time bias in the statistical approach, selection of
unsuitable control groups, no consideration of external trends). The EUROSCREEN
Group analysed the literature on this topic, paying particular attention to the
correct methodology, and estimated the rate of overdiagnoses as 1–10 %, 6 % on
average [30].
Reliable estimates regarding the frequency of overdiagnoses may come to between 5
and 20 % of all cancer diagnoses [2], [30], [33], [34]. Overall, it should be emphasised that, due to the
strong influence of the calculation methodology and the controversial and
discrepant results in the literature, the existing evidence should be classed as
very low with regard to the calculation of overdiagnoses. The scientific data
currently available on this subject are thus clear and are inconsistent with the
views of screening opponents.
Overview and absolute figures
Percentage information, both from screening opponents and screening advocates, is
used. This can vary significantly depending on the reference basis and lead to
relative distortions with a changing reference basis, producing a false
image.
An overview is provided below of the absolute frequencies of positive and
negative effects to be expected from screening ([Table
3]). It is important to understand that, although breast cancer can
affect one in 9 women in their lives (lifetime risk approx. 11 %), the annual
risk (annual!) is low at 3/1000. This shows the need for regular examinations of
many asymptomatic women if one wishes to detect breast cancer early or in good
time.
Table 3 Overview with regard to the numerical data to be
expected in the screening (absolute values for 20 years of screening
among 1 000 participants). The values come from the review by the
EUROSCREEN Working Group [3] and include
the median values in the German Screening Programme with regard to
diagnoses. 19 women[2] die without
screening in the control group; 11 (10 to 12) women[2] die in the screened group. This
corresponds to 8 lives saved among 1 000 screening participants or a
mortality reduction of approx. 43 %.
|
|
With screening (P)
|
Without screening (N-P)
|
Difference
|
|
Number of women
|
1 000
|
1 000
|
|
|
Mammograms/20 years
|
10 000
|
unknown
|
|
|
Call-backs for any diagnosis due to benign changes
|
288 (incl. biopsies)
|
unknown
|
|
|
of which:
|
|
|
|
|
|
74
|
unknown
|
|
|
|
71
|
67
|
4 (− 14)
|
|
|
11
|
19
|
7 to 9
|
Below, 1000 women who take part in the screening over 20 years (P) are compared
with 1000 women who do not take part (N-P).
The participants undergo a mammogram every 2 years (= 10,000 screening mammograms
in 20 years between 50–69).
As a result of a benign finding[1], 288 women on
average are invited for diagnosis once in 20 years (28.8/1000 per cycle
or almost 3 %), of which 74 (7.4 per cycle[2]) have
to undergo a histological investigation once in 20 years due to a benign
finding.
According to the calculations by the EUROSCREEN Group, an average of 71 breast
cancers are found in Ps (approx. 56 in the screening and 15 in the interval),
while there are an average of 67 breast cancers in the control group (N-Ps)
(taking into account an adequate follow-up period). The difference of 4
carcinomas thus corresponds to the overdiagnoses. (These are actual breast
cancers that would not be detected during the womanʼs lifetime without
screening. According to calculations by the UK panel, it could be up to 14[3].)
A relevant proportion of the 56 women with breast cancer discovered in the
screening may benefit from earlier discovery (more breast retention, fewer
axillary dissections, less chemotherapy due to discovery at an earlier stage).
There are no model calculations available here.
19 women[2] die without screening in the control
group; 11 (10 to 12) women[2] die in the screened
group. This corresponds to 8 lives saved among 1,000 screening participants or a
mortality reduction of approx. 43 %.
Discussion
Since its introduction between 2005 and 2009, mammography screening has become
increasingly established in Germany. The outcome parameters of the German
Mammography Screening Programme fulfil the requirements of the EU Guidelines and
also show very good results ([Tables 1] and [2]) by international comparison.
In view of the astoundingly high rate of carcinomas discovered (despite opportunistic
grey screening, which exists in parallel), not only can it be argued that there is a
generally slightly higher diagnosis rate using imaging investigations compared with
other screening countries, but this also lies within the scope of the limit values
specified by the EU Guidelines. The biopsy rate calculated for the German programme
appears high with regard to the whole programme, but is distorted by the high number
of first examinations, for which higher biopsy rates must be applied. The
gratifyingly high proportion of minimally invasive biopsies among the histological
investigations in the German programme is to be noted. This may be due to the early
inclusion of vacuum biopsy, as well as to the introduction of digital screening, for
both of which Germany proved to be a pioneer in Europe. Data on mortality reduction
or overdiagnoses are not to be expected yet, as coverage was only achieved in 2009.
According to current knowledge (based on stage distribution and detection rates), it
is to be expected that the German programme can achieve comparable effects to those
seen in other quality-assured screening programmes in Europe.
In general, both positive effects and possible side effects are to be expected from
screening programmes (as is the case for other medical measures).
Following countless attacks against the Mammography Screening Programme, an
independent British panel has since confirmed that the mortality reduction
calculated using randomised studies and specified by WHO (approx. 30 % for the
actual participant) continues to be valid. The EUROSCREEN Working Group was able to
calculate a mortality reduction of approx. 43 % for the current quality-assured
screening programmes using the data from 18 countries ([Table
3]). All the data available so far indicate that the programme is highly
effective, including in Germany.
A mortality reduction of 43 % corresponds to approx. 8 lives saved per 1000 screening
participants. (It should be taken into account here that only 70 breast cancers
occur among 1000 participants within the 20 screening years between 50–69, of which
approx. 19 are fatal without screening.)
Information from screening opponents, who claim a “benefit” among “just 1/1000” women
or a similarly low efficacy, does not correspond to the data resulting from all of
the meta-analyses and randomised studies [2], and relates
to other periods of time or another age group (e.g. 10 years of screening among
under-40s, etc.) The advantages of earlier treatment are also ignored.
The radiation dose, which is often stated as the primary disadvantage, should still
not be an argument against screening when applied correctly due to the very low risk
and significant benefits [21], [22], [23]. Warnings should be issued about
so-called IGeL mammograms (with questionable application in some cases, e.g. due to
low-dose mammography or a “wellbeing factor”) due to the lack of quality assurance
and thus also uncertain effects.
If breast cancer is to be discovered at an early stage, further investigations with a
certain number of ultimately benign changes (as for almost all medical tests) are
unavoidable. Call-backs are necessary during the screening for this reason.
Fortunately, quality-assured mammography screening has a very high specificity, so
only approx. 30/1000 women need to be called back per screening cycle. Based on the
screening period, this means that almost 300 women are called back once (i.e.
in 10 screening cycles) within 20 years due to an ultimately benign finding.
Quality-assured investigations in mammography screening take place in as minimally
invasive a manner as possible (mostly without biopsies, otherwise usually with
minimally invasive biopsy techniques). Approximately one in every two needle
biopsies demonstrates a malignant tumour. If one contrasts these disadvantages with
the benefit of saving lives and the less invasive treatment on earlier diagnosis,
the stress of investigation is medically low and highly justifiable. A close
collaboration between the screening unit and the treating gynaecologists and GPs
should absolutely be strived for in order to bypass any possible short-term, highly
individual mental stress experienced by the patient between the invitation and
investigation.
There is actually no other diagnostic method with such high specificity as the
Mammography Screening Programme. If one compares ultrasound and MRI when used for
the early detection of breast cancer with mammography, it is initially to be noted
that there is a lack of prospective studies among asymptomatic women without an
increased risk. Among risk collectives it can be seen that, depending on the risk
constellation, sensitivity can be increased using supplementary methods. However,
specificity falls considerably when other methods are added. With mammography alone,
significantly fewer invasive investigations (> factor 3) are required, in
particular [25], [38].
Recommendations for short-term check-ups (where stated in the literature) are, in
some cases, more than 10 times higher for sonographic and MRI investigations than
for mammography [38], [39].
A further unwanted effect of every screening investigation that is relevant when
applying sensitive test procedures (i.e. procedures that can identify cancer long
before it is palpable) is what is known as overdiagnosis. Overdiagnoses are thus to
be expected with any early detection method (including grey screening), but, in
principle, cannot be determined due to a lack of data. They occur when breast cancer
is discovered very early using imaging (or another test) and/or grows very slowly,
so the woman would not have known about it during her lifetime without screening. An
excessively high number of overdiagnoses is to be avoided as it does not contribute
to a reduction in mortality, yet the patient is placed under unnecessary stress by
the knowledge of her breast cancer and the treatment. Unfortunately, all estimates
are tainted by significant calculatory fluctuation margins due to the uncertain
state of data. The current discussion regarding overdiagnoses [31], which are even incorrectly shown as wrongly diagnosed breast cancer
in some cases, is scientifically incomprehensible and hardly defensible medically in
terms of the patient in light of the very low evidence level that exists.
In view of the benefits, the number of overdiagnoses ascertained according to
reliable calculations appears to be absolutely justifiable in medical terms. It is
important to understand that it is not possible to predict for any individual woman
whether the very early diagnosis of breast cancer benefits her (by saving her life
and through better treatment options) or could be an overdiagnosis. Discovery and
appropriate treatment therefore remain sensible and important. The “damage” of an
overdiagnosis is actually closely linked to the treatment that follows it.
Chemotherapy and axillary dissections are usually rare, especially in the case of
early breast cancers. However, with increasingly earlier discovery, it is
particularly important that treatment is adjusted optimally to suit the individual
risk of the patient.
Despite the high sensitivity of mammography, interval carcinomas are unavoidable.
Through appropriate investigation, it should be ensured that clinical findings
undergo a further investigation, even after a screening mammogram without
pathological findings.
Although it is known that additional breast cancer cases can be found with sonography
or MRI, pure sonography or MRI-based screening is currently not possible due to
their far lower specificity and the as yet insufficient quality assurance for
screening.
The first encouraging results have been reported on the prospective application of
tomosynthesis, a mammographic method whereby tomographic images of the breast are
produced [36], [37].
Regardless of the discussions generated by screening critics (these are actually
opponents of any early detection measures), quality-assured mammography screening
proves to be a sensible and important measure. Any side effects and limits are to be
taken into account and minimised. It should be explicitly noted that any side
effects of screening apply at least equally to grey screening, although the effects
and side effects cannot be verified for this, nor can the quality appropriate for
early detection. Although acceptance of screening is high among screening
participants [24], the national participation rate should
be further increased from the recently published 54 % of women. Gynaecologists, in
particular, can perform important clarification work here.
Future research should be concentrated on possible and sensible amendments,
especially to reduce interval carcinomas and late stages. The optimal adjustment of
treatment is important for small breast cancers discovered at an especially early
stage. A reduction in stressful treatments should be looked at here using suitable
studies.
