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Overdiagnosis in mammography
screening for breast cancer in Sweden
and Norway
Senior Statistician Per-Henrik Zahl, MA MD PhD
Norwegian Institute of Public Health
Professor Jan Mæhlen, MD PhD
Department of Pathology, Ullevål University
Hospital
July 29th, 2004
The aim of mammography screening is to diagnose the
tumour when it is small and before tumour spread occurs
since such small stage I tumours have favourable prognosis.
Many small tumours (stage I) are detected at
the mammography screening
Mammogramme with
small breast cancer (T)
Macroscopic picture of excised
tumor (T)
T
T
Background
• Prior to the introduction of mammography
screening in Sweden and Norway the breast
cancer incidence increased less than 1%
annually (Rostgaard et al, Stat Med 2001)
• Coinciding with the introduction of
mammography screening the incidence of
breast cancer in the invited age group 50-69
years increased about 50% (Zahl, Strand,
Mæhlen BMJ 2004)
Ductal breast carcinoma
Lobular breast carcinoma
Definition:
Overdiagnosis is the diagnosis of disease that
(without screening) would not have given
symptoms during the lifetime of the patient
May these three factors explain the
incidence increase?
• There was an underlying increase in breast
cancer incidence rates in the periods before the
screening programmes started.
• In the first screening round a large number of
slow-growing tumours that would have occurred
in the future are diagnosed earlier.
• In the following screening rounds some excess of
breast cancer will persist due to a combined
effect of lead-time and incidence increase with
age.
While the Swedish mammography screening programme
started in 1986, the Norwegian programme started in 1996.
Per cent
100,0
90,0
Sweden
Norway
80,0
70,0
Screening start
in Sweden
60,0
50,0
40,0
Screening start
in Norway
30,0
20,0
10,0
20
02
20
00
19
98
19
96
19
94
19
92
19
90
19
88
19
86
19
84
19
82
19
80
19
78
19
76
19
74
0,0
Year
Estimation of the level of overdiagnosis
• Overdiagnosis is calculated as the incidence
increase in the screened age group minus the
subsequent incidence decline that occurs when
these women reach the age when they are no
longer invited to screening. If no overdiagnosis
occurs, this difference should be zero.
• The level of overdiagnosis can also be estimated
as the proportion of the total cancer cases that
would not have been diagnosed in the absence
of screening.
During the introduction of mammography screening in
Sweden the breast cancer incidence increased by nearly 50%
in the screened age group. No similar fall in breast cancer
incidence in women above age 70 years has emerged.
Incidence per 100 000
women
400
350
Sweden 70+
300
250
Sweden 50-69
200
150
100
Sweden 30-49
50
19
71
19
73
19
75
19
77
19
79
19
81
19
83
19
85
19
87
19
89
19
91
19
93
19
95
19
97
19
99
20
01
0
Overdiagnosis in the Swedish screening
programme
• The incidence increase is 50% in the age group 50-69
years.
• The incidence decline is 0% in the age group 70-74
years and 12% in the age group 75-79 years. This
decrease compensates less than 3% of the incidence
increase in the screened age group. No incidence
decline is expected among women above age 79
years.
• We conclude that nearly all of the incidence increase
in Sweden are caused by cancers that would not
have been diagnosed in the absence of screening.
During the introduction of mammography screening in Norway
the breast cancer incidence increased >50% in the screened age
groups. Only an 11 % reduction in breast cancer incidence
occurred in previously screened women aged 70-74 yrs in 2000-1.
Incidence per 100 000
women
400
AORH-counties
350
Norway 70+
300
250
200
Norway 50-69
Non-AORH-counties
150
100
Norway 30-49
50
0
1971 1973 1975 1977 1979 1981 1983 1985 1987 1989 1991 1993 1995 1997 1999 2001
Table 1
RR
95% CI
AORH counties
1991 (reference)
1.0
Annual increase 1992-95
1.01
0.99 – 1.02
1996-97 (prevalence screening)
1.82
1.70 – 1.96
1998-99 (second screening)
1.54
1.42 – 1.66
2000-1 (third screening)
1.52
1.39 – 1.65
0.87
0.73 – 1.03
Age 50-69 years
Age 70-74 years
2000-1
Overdiagnosis in the Norwegian
screening programme (AORH-counties)
• The incidence increase is 52-54% in the age group
50-69 years.
• The incidence decline is 13% in the age group 70-74
years. This decline compensates only 3% of the
increase in the screened age group. No incidence
decline is expected in women above age 74 years.
• We conclude that nearly all of the incidence
increase in Norway are caused by cancers that
would not have been diagnosed in the absence of
screening.
Incidence rates among those attending and those not
attending screening in the age group 50-69 years in
four Norwegian counties
Incidence per 100
000 women
400
350
300
250
200
150
100
50
0
Before screening Not attending
Second
(1991-95)
screening (1996- screening round
2001)
(1998-99 )
Third screening
round (2000-1)
Definition of interval cancer
• Interval cancer is breast cancer detected clinically
in the time interval between two mammography
screenings.
• The incidence rate of interval cancer in the
Norwegian screening programme has been 190
cases per 100 000 per 2 year (i.e. close to 50% of
the predicted rate in the absence of screening).
• Compared to the incidence rate of cancer in the
absence of screening, the rate of interval cancer is
30% in the first year and 70% in the second year
after screening.
Cancer incidence in those leaving the
screening program at age 69 years reflects the
interval cancer incidence
If the incidence reduction is 70% in the
first year, 30% in the second year, 15 %
in the third year, 5% in the fourth year
and return to the background in the fifth
year, the overall reduction in age group
70-74 year is 13% (assuming 75%
attendance rate at the last screening at
age 68-69 years).
Lead-time
• Lead-time is defined as the time the diagnosis
is brought forward by the screening.
• The average lead-time in the randomized trials
has been estimated to about 4 years.
• When we adjust for overdiagnosis in the
Norwegian programme, we estimated lead-time
to be 1.2 years.
• The high rate of interval cancer at the end of a
screening interval support the idea that the
lead-time is short.
Is it sensible to expect a mortality
reduction when
• The average lead time in the Norwegian
screening programme after adjusting for
overdiagnosis is much smaller than in the
screening trials; 1.2 years vs. 4 years.
• The rate of interval cancer in the Norwegian
screening programme is much higher than in
the screening trials (the rate in the Norwegian
programme is twice the rate in the Swedish
WE-study).
In the randomized screening trials the mortality decline
was observed after four years. Since Sweden started
mammography screening more than ten years before
Norway one would expect:
1. In the 1990s the decline in the Swedish breast
cancer mortality rates should be substantially
larger than the decline in the Norwegian rates.
2. In Sweden the breast cancer mortality rates
should decline substantially more in the age
group 55-74 years than in the other age groups.
As shown in the next slide none of these phenomena have
been observed.
Age-adjusted breast cancer mortality rates in Norway and
Sweden in 1978-2001 for the age groups 45-54, 55-74 and
75-84 years
160
Deaths
per
100 000
120
Age 75-84
years
80
Age 55-74
years
Age 45-54 years
40
0
1978
1980
1982
1984
1986
1988
1990
1992
1994
1996
1998
2000
What is known about overdiagnosed
cancers in other locations?
• Screening for prostate cancer leads to 30%
overdiagnosis (Etzioni et al, JNCI 2002). In this organ
sub-clinical cancer is very frequent at autopsy
(prevalence 50% after age 80 years, Liavag I, Harbitz TB,
Haugen OA. Latent carcinoma of the prostate. Recent
Results Cancer Res. 1972;39:131-7).
• Screening of children for neuroblastoma leads to
substantial overdiagnosis. For such tumours
spontaneous regression without treatment is the most
likely outcome, therefore these patients do not benefit
from earlier diagnosis (Schilling et al, N Eng J Med 2002).
– After three biennial screenings in Norway
the accumulated breast cancer incidence
was substantially higher than the
accumulated breast cancer incidence after
prevalence screening of previously unscreened women.
– This observation suggests that in the
absence of screening many small and
localized invasive breast cancers undergo
spontaneous regression.
Summary
• Overdiagnosis of breast cancer in national
mammography screening programmes is
substantial.
• In Sweden the decline in breast cancer mortality
rates after 10-15 years of screening is much smaller
than expected from the randomized trials. In fact, a
very similar small decline in breast cancer mortality
has also occurred in Norway before the screening
started.
• Our results show that many small tumours
detected by mammography behave as benign
lesions although they fulfill the histological criteria
for invasive cancers. We propose that such lesions
normally undergo spontaneous regression.