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FIGURE LEGENDS
Figure 5a: Observed (dots) and model-fitted (line) breast cancer incidence.
Figure 6a: Relative stage-specific mortality from breast cancer and fitted negative exponential functions with
95% confidence limits.
Figure 7a: The distributions of 10,000 random sets of QALY weights (Beta distributions) used in the model.
Figure 8a: The distributions of 10,000 random sets of costs (log-normal distributions) used in the model
(Note the different scale for the costs of chemotherapy)
Figure 9a: The distributions of 10,000 random sets of sojourn times (log-normal distributions) and probabilities
(Beta distributions) used in the model.
Figure 10a: Results of probabilistic sensitivity analysis (small dots) for screening policies 4, 16 and 33 on the
cost-effectiveness plane with results of base case analysis (large dots) incrementally to no-screening.
Figure 11a: Graphical presentation of the breast cancer cumulative mortality and the portion of women who were
diagnosed as false positive during their life-course in populations that are screened from 40 to 80 years of age
by 1, 2 or 3 year intervals and in the population that is not screened. The cumulative mortality for the 2-year
interval policy is lower than cumulative mortality of 3 year interval policy and higher than cumulative mortality of 1
year interval policy. The percentage of women refers to the total number of women alive at the age of 40.
Figure 5a: Observed (dots) and model-fitted (line) breast cancer incidence.
Figure 6a: Relative stage-specific mortality from breast cancer and fitted negative exponential functions with
95% confidence limits.
Figure 7a: The distributions of 10,000 random sets of QALY weights (Beta distributions) used in the model.
Figure 8a: The distributions of 10,000 random sets of costs (log-normal distributions) used in the model
(Note the different scale for the costs of chemotherapy)
Figure 9a: The distributions of 10,000 random sets of sojourn times (log-normal distributions) and probabilities
(Beta distributions) used in the model.
Figure 10a: Results of probabilistic sensitivity analysis (small dots) for screening policies 4, 16 and 33 on the
cost-effectiveness plane with results of base case analysis (large dots) incrementally to no-screening.
Figure 11a: Graphical presentation of the breast cancer cumulative mortality and the portion of women who were
diagnosed as false positive during their life-course in populations that are screened from 40 to 80 years of age
by 1, 2 or 3 year intervals and in the population that is not screened. The cumulative mortality for the 2-year
interval policy is lower than cumulative mortality of 3 year interval policy and higher than cumulative mortality of 1
year interval policy. The percentage of women refers to the total number of women alive at the age of 40.
TABLES
Table 2a: Treatment distribution by breast cancer stage [1] indicates the portion of women in each cancer stage
that were treated with specific intervention.
Chemotherapy
Hormonal therapy
Surgery
Radiotherapy
Local stage
29%
43%
88%
39%
Regional stage
66%
57%
89%
52%
Distant stage
58%
61%
20%
60%
Table 3a: Costs and QALYs used in each Markov State of the model.
Markov State
QALY
Costs
No breast cancer
1
None**
1
None**
According to treatment
Costs of diagnostics for clinically detected
cancers and costs of treatment
According to treatment
Costs of mammography examination and
costs of treatment
QALY (Diagnostic phase)
Costs of mammography examination and
costs of invasive diagnostics
-DCIS
Preclinical screen
detectable breast
cancer
-Local stage
-Regional stage
-Distant stage
-Local stage
Clinically detected
-Regional stage
breast cancer
-Distant stage
-DCIS
Screen detected
breast cancer
-Local stage
-Regional stage
-Distant stage
False positive
from breast cancer
QALY (Terminal illness)*
Death
None
from other causes
0
* The QALY (Terminal illness) was used in the month before the death.
**If the women are screened (according to screening policy and attendance), the costs of mammography
examination are included. If the women are recalled for non-invasive diagnostics, the cost of non-invasive
diagnostics is also included.
Table 4a: Baseline incremental costs and effects (in terms of LYS and QALY) relative to no-screening, which has
cost of €231 and effects of 23.0 QALYs or 23.1 LYS and efficiency frontier.
Screening
To
By
year
years
65
3
incremental to no screening
33
From
year
50
29
45
65
3
0.0518
0.0465
230.6
30
45
70
3
0.0583
0.0521
268.2
26
40
70
3
0.0701
0.0626
358.5
27
40
75
3
0.0718
0.0640
372.7
28
40
80
3
0.0737
0.0654
394.3
16
40
80
2
0.0797
0.0697
585.0
1
40
65
1
0.0745
0.0587
929.6
2
40
70
1
0.0769
0.0626
1,020.7
3
40
75
1
0.0809
0.0646
1,090.3
4
40
80
1
0.0812
0.0654
1,140.1
5
45
65
1
0.0595
0.0483
684.0
6
45
70
1
0.0663
0.0522
776.2
7
45
75
1
0.0676
0.0542
846.4
8
45
80
1
0.0694
0.0549
896.8
9
50
65
1
0.0458
0.0350
474.9
10
50
70
1
0.0485
0.0388
568.0
11
50
75
1
0.0524
0.0409
639.1
12
50
80
1
0.0528
0.0416
689.9
13
40
65
2
0.0691
0.0611
470.3
14
40
70
2
0.0756
0.0665
525.6
15
40
75
2
0.0780
0.0684
554.0
17
45
65
2
0.0579
0.0511
354.9
18
45
70
2
0.0623
0.0547
391.8
19
45
75
2
0.0659
0.0576
434.9
20
45
80
2
0.0671
0.0584
455.6
21
50
65
2
0.0412
0.0362
238.2
22
50
70
2
0.0477
0.0415
294.2
23
50
75
2
0.0501
0.0435
322.9
24
50
80
2
0.0518
0.0447
354.3
25
40
65
3
0.0642
0.0576
322.7
31
45
75
3
0.0617
0.0547
296.0
32
45
80
3
0.0625
0.0553
306.4
34
50
70
3
0.0434
0.0386
191.2
35
50
75
3
0.0471
0.0416
220.7
36
50
80
3
0.0487
0.0428
240.9
LYS
QALY
Cost (€)
0.0403
0.0359
172.8
incremental to less costly policy
ICER
QALY
Cost (€)
(€/QALY)
0.0359
172.8
4,813
Efficiency frontier
Policy
0.0106
57.8
5,457
0.0056
37.6
6,751
0.0105
90.3
8,568
0.0014
14.2
9,872
0.0014
21.6
15,516
0.0042
190.7
45,101
Dominated policies
RESULTS OF THE UNIVARIATE SENSITIVITY ANALYSIS
Table 5a: Structure of the efficiency frontiers in 82 different univariate sensitivity analyses
Frequency on
Screening
the efficiency
policy
frontiers
Cases in which the screening policy is on the efficiency frontier
33
81
In all cases except when sensitivity for 50-59 years is at lower limit
29
81
In all cases except when sensitivity for 40-49 years is at lower limit
30
80
In all cases except when discounting is 1%, and when sensitivity for 60-69 years is at
lower limit
25
3
Only when discounting is 1%, when sensitivity for 40-49 years is at upper limit and
when Portion of DCIS that progress to preclinical Local stage is at lower limit
26
82
In all cases
27
82
In all cases
15
1
Only when the sojourn time in local stage is at lower limit value
28
81
In all cases except when the sojourn time in local stage is at lower limit value
16
81
In all cases except when the sojourn time in local stage is at upper limit value
Table 6a: Average impact of input parameters at their lower/upper range values on the ICER values for
screening policies 33, 29, 30, 26, 27, 28 and 16. Note that for parameters marked with *, the lower limits of
parameters increased the ICER and the upper limits decreased the ICER.
Parameter
Discounting
Portion of DCIS that progresses to preclinical Local stage*
Recall rate
Relative mortality in regional stage (parameter B)*
Relative mortality in regional stage (parameter A)*
Percent of invasive diagnostics at recall
Cost of mammography exam
Portion of invasive cancers. that are not preceded by DCIS
Portion of clinically detected cancers in local stage
Sojourn time in DCIS stage
Cancer incidence*
Cost of invasive diagnostics
Relative mortality in local stage (parameter A)
Portion of clinically detected cancers in regional stage
Relative mortality in local stage (parameter B)
Sojourn time in regional stage
Cost of non-invasive diagnostics
Sensitivity above 70 years*
QALY (Diagnostic phase)*
Cost of chemotherapy*
Sojourn time in distant stage
Sensitivity for 50-59 years of age*
QALY (Hormonal therapy)
Sensitivity for 40-49 years*
Attendance
Cost of diagnostics for clinically detected cancers*
Sensitivity for 60-69 years of age*
QALY (Chemotherapy)
Cost of radiotherapy*
Cost of surgery
QALY (Distant stage breast cancer )
QALY (Terminal illness)
Cost of hormonal therapy*
QALY (Radiotherapy)
QALY (2m-1year after surgery)
Portion of clinically detected cancers in distant stage
QALY (Surgery)
QALY (Disease free>1year after operation)
Relative mortality in distant stage (parameter B)
Relative mortality in distant stage (parameter A)
Sojourn time in local stage
Input parameter range
1%
5%
90.4%
33.4%
1.4%
16.6%
0.162
0.094
0.862
0.592
4.7%
42.8%
€44
€66
13.3%
70.6%
38.1%
44.0%
3
7
+10%
-10%
€320
€1560
0.221
0.293
44.1%
49.9%
0.125
0.193
0.36
1.08
€47
€154
98.3%
79.2%
0.997
0.653
€13500
€605
0.35
1.04
99.5%
80.9%
0.472
0.991
94.8%
75.5%
60.1%
87.3%
€957
€55
99.7%
81.1%
0.309
0.975
€4630
€2650
€2320
€2900
0.410
0.620
0.004
0.833
€7180
€395
0.486
0.981
0.518
0.994
8.1%
16.1%
0.578
0.995
0.777
0.999
0.680
0.762
0.814
0.838
3
2
ICER range
68%
147%
81%
141%
79%
131%
86%
127%
84%
126%
87%
117%
84%
116%
96%
115%
90%
113%
89%
113%
90%
112%
88%
112%
93%
109%
93%
108%
93%
107%
95%
105%
97%
105%
98%
105%
98%
104%
84%
104%
98%
102%
99%
102%
96%
102%
98%
102%
99%
102%
96%
102%
99%
101%
98%
101%
99%
101%
99%
101%
99%
101%
100%
101%
93%
100%
100%
100%
100%
100%
100%
100%
100%
100%
100%
100%
100%
100%
100%
100%
98%
96%
SECTION A:
POSSIBLE LIFE-COURSES OF WOMEN IN POPULATION WITHOUT SCREENING AND IN POPULATIONS
WITH SCREENING
Population without screening
Most common life course of women in population without screening is healthy life until death. Some women
develop a breast cancer, according to breast cancer incidence. A portion of invasive breast cancers is preceded
by DCIS, which is non-invasive and can spontaneously regress. The remaining breast cancers start as invasive
from the beginning. When the local stage invasive breast cancer has developed, it may progress to regional
stage breast cancer or it may be clinically detected and treated. Likewise, the regional stage breast cancer can
progress to distant stage breast cancer or it may be clinically detected and treated. Women with distant stage
breast cancer are then also diagnosed clinically and treated accordingly.
Death from breast cancer can occur only when women are diagnosed with breast cancer; that is when they are
in clinical local, regional or distant stage. At any given time of their life course, women can die because of other
causes than breast cancer.
Population with screening
The life courses of women in population that is screened is related to life course of population without screening,
except that the DCIS and the preclinical stages of invasive breast cancer can be detected with screening, thus
diagnosing the women with breast cancer earlier in their lifetime. New life course is also the path of false positive
women, which had positive screening examination but no cancer is found at further invasive diagnostic
assessment. Even though that the majority of breast cancers are diagnosed with screening, some breast
cancers are also diagnosed clinically. The breast cancers are diagnosed clinically in women who develop breast
cancer and do not attend the screening, when they have false negative results at their screening or when the
period between screening intervals is long enough to permit the development of the breast cancer. The
treatment and the survival of the clinically detected and screen detected breast cancers is the same.
MODEL PARAMETERS AND TRANSITIONS
Transitions used in the model (1 week cycle length)
Transition from all alive states to state ''death from other causes''= 2.85  10
7
 exp 0.103  age
Transition from ''healthy'' state to states ''preclinical DCIS and preclinical Local stage''
2


from ages 25-59 = 4.3  10 5  exp   51  age   and for
2


2  10


2


ages above 59 = 6.0  10 5  exp   74  age  


2  24 2


(Note: this probability describes the transition to either preclinical DCIS or to preclinical Local stage. The portion
of transitions to either state is then defined by PDCIS1(see below))
Relative stage-specific mortality from breast cancer
A negative exponential function was fitted to stage-specific breast cancer relative mortality, and fitted parameters
distributions were used to describe the distributions of relative mortality at specific times after the diagnosis.
% of women dead because of breast cancer= A  1  exp B  years after diagnosis
Local stage
A (Mean ± St. Dev.)
0.257+0.0184
B (Mean ± St. Dev.)
0.159+0.0174
Regional stage
0.727+0.0687
0.128+0.0171
Distant stage
0.826+0.00595
0.721+0.0210
Clinical stage distribution
Portion of clinically detected cancers in Local/Regional/Distant stages:
Plocal
Pregional
Pdistant
Beta distribution
α
β
440
634
520
586
1-Plocal-Pregional
2.5%
Quantile
38.1%
41.0%
97.5%
Quantile
44.0%
44.1%
47.0%
49.9%
8.1%
12.0%
16.1%
Mean
Transitions between preclinical screen-detectable stages and transitions from preclinical to clinical stages are
then determined by following formulas:
Ppreclinical localclinical local=Plocal
Ppreclinical localpreclinical regional=1-Plocal
Ppreclinical regionalclinical regional=Pregional / (1-Plocal)
Ppreclinical regionalpreclinical distant=1- Pregional / (1-Plocal)
Ppreclinical distantclinical distant=100%
Note: the transition probabilities represent the portion of women, who move between states after stage specific
sojourn time.
Portion of invasive cancers that are not preceded by DCIS:
Beta distribution
2.5%
α
β
Quantile
PDCIS1
3.87
5.80
13.3%
Portion of DCIS that progress to preclinical Local stage (invasive cancer):
Beta distribution
2.5%
α
β
Quantile
PDCIS2
5.92
3.19
33.4%
Mean
40.0%
Mean
65.0%
97.5%
Quantile
70.6%
97.5%
Quantile
90.4%
Sojourn times (years)
Log-normal distribution
=exp of normal distribution with
2.5%
Quantile
Mean
97.5%
Quantile
3
5
7
STDCIS
Mean
5.54
St. Dev.
0.217
STLocal
4.86
0.101
2
2.5
3
STRegional
3.61
0.259
0.36
0.73
1.08
STDistant
3.55
0.277
0.35
0.70
1.04
Screening characteristics:
Attendance
Beta distribution
α
β
27.9
9.32
Recall rate
2.78
36.9
Invasive diagnostics
among recalled women
3
12
2.5%
Quantile
60.1%
75%
97.5%
Quantile
87.3%
1.4%
7%
16.6%
4.7%
20%
42.8%
Mean
Screening sensitivity:
women aged 40-49 years
Beta distribution
α
β
39.1
6.00
women aged 50-59 years
21.5
1.47
80.9%
93.6%
99.5%
women aged 60-69 years
20.0
1.25
81.1%
94.1%
99.7%
women older than 70 years
28.4
2.74
79.2%
91.2%
98.3%
2.5%
Quantile
75.5%
86.7%
97.5%
Quantile
94.8%
Mean
QALY weights and durations of disease/treatment phases [25,26]:
Beta distribution
α
β
0.746
1.85
2.5%
Quantile
0.00367
0.288
97.5%
Quantile
0.833
Mean
Terminal illness
1 month
Distant stage breast cancer
life expectancy
44.3
41.7
0.410
0.515
0.620
Chemotherapy
6 months
3.73
1.47
0.309
0.717
0.975
Radiotherapy
2 months
6.42
1.58
0.486
0.803
0.981
Hormonal therapy
2 years
5.31
1.17
0.472
0.820
0.991
2m-1year after surgery
10 months
5.80
1.07
0.518
0.844
0.994
Surgery
2 months
6.96
1.07
0.578
0.867
0.995
Diagnostic phase
5 weeks
8.82
1.04
0.653
0.895
0.997
Disease free>1year after operation
life expectancy
11.9
0.670
0.777
0.947
0.999
Costs of mammography examination, diagnostic procedures and treatments (Euros (€)) [1]:
Log-normal distribution
=exp of normal distribution with
Mean
St. Dev.
2.5%
Quantile
Mean
97.5%
Quantile
55
Mammography examination
Invasive diagnostic procedures
6.86
0.648
320
1176
1560
Noninvasive diagnostic procedures
4.5
0.596
47
107
154
Diagnostics for clinically detected cancers
5.74
1.19
55
635
957
Surgery
7.85
0.06
2320
2582
2900
Radiotherapy
8.19
0.169
2650
3641
4630
Hormonal therapy
6.61
0.975
395
1191
7180
Chemotherapy
8.04
0.909
605
4680
13500
TABLES
Table 2a: Treatment distribution by breast cancer stage [1] indicates the portion of women in each cancer stage
that were treated with specific intervention.
Chemotherapy
Hormonal therapy
Surgery
Radiotherapy
Local stage
29%
43%
88%
39%
Regional stage
66%
57%
89%
52%
Distant stage
58%
61%
20%
60%
Table 3a: Costs and QALYs used in each Markov State of the model.
Markov State
QALY
Costs
No breast cancer
1
None**
1
None**
According to treatment
Costs of diagnostics for clinically detected
cancers and costs of treatment
According to treatment
Costs of mammography examination and
costs of treatment
QALY (Diagnostic phase)
Costs of mammography examination and
costs of invasive diagnostics
-DCIS
Preclinical screen
detectable breast
cancer
-Local stage
-Regional stage
-Distant stage
-Local stage
Clinically detected
-Regional stage
breast cancer
-Distant stage
-DCIS
Screen detected
breast cancer
-Local stage
-Regional stage
-Distant stage
False positive
from breast cancer
QALY (Terminal illness)*
Death
None
from other causes
0
* The QALY (Terminal illness) was used in the month before the death.
**If the women are screened (according to screening policy and attendance), the costs of mammography
examination are included. If the women are recalled for non-invasive diagnostics, the cost of non-invasive
diagnostics is also included.
Table 4a: Baseline incremental costs and effects (in terms of LYS and QALY) relative to no-screening, which has
cost of €231 and effects of 23.0 QALYs or 23.1 LYS and efficiency frontier.
Screening
To
By
year
years
65
3
incremental to no screening
33
From
year
50
29
45
65
3
0.0518
0.0465
230.6
30
45
70
3
0.0583
0.0521
268.2
26
40
70
3
0.0701
0.0626
358.5
27
40
75
3
0.0718
0.0640
372.7
28
40
80
3
0.0737
0.0654
394.3
16
40
80
2
0.0797
0.0697
585.0
1
40
65
1
0.0745
0.0587
929.6
2
40
70
1
0.0769
0.0626
1,020.7
3
40
75
1
0.0809
0.0646
1,090.3
4
40
80
1
0.0812
0.0654
1,140.1
5
45
65
1
0.0595
0.0483
684.0
6
45
70
1
0.0663
0.0522
776.2
7
45
75
1
0.0676
0.0542
846.4
8
45
80
1
0.0694
0.0549
896.8
9
50
65
1
0.0458
0.0350
474.9
10
50
70
1
0.0485
0.0388
568.0
11
50
75
1
0.0524
0.0409
639.1
12
50
80
1
0.0528
0.0416
689.9
13
40
65
2
0.0691
0.0611
470.3
14
40
70
2
0.0756
0.0665
525.6
15
40
75
2
0.0780
0.0684
554.0
17
45
65
2
0.0579
0.0511
354.9
18
45
70
2
0.0623
0.0547
391.8
19
45
75
2
0.0659
0.0576
434.9
20
45
80
2
0.0671
0.0584
455.6
21
50
65
2
0.0412
0.0362
238.2
22
50
70
2
0.0477
0.0415
294.2
23
50
75
2
0.0501
0.0435
322.9
24
50
80
2
0.0518
0.0447
354.3
25
40
65
3
0.0642
0.0576
322.7
31
45
75
3
0.0617
0.0547
296.0
32
45
80
3
0.0625
0.0553
306.4
34
50
70
3
0.0434
0.0386
191.2
35
50
75
3
0.0471
0.0416
220.7
36
50
80
3
0.0487
0.0428
240.9
LYS
QALY
Cost (€)
0.0403
0.0359
172.8
incremental to less costly policy
ICER
QALY
Cost (€)
(€/QALY)
0.0359
172.8
4,813
Efficiency frontier
Policy
0.0106
57.8
5,457
0.0056
37.6
6,751
0.0105
90.3
8,568
0.0014
14.2
9,872
0.0014
21.6
15,516
0.0042
190.7
45,101
Dominated policies
RESULTS OF THE UNIVARIATE SENSITIVITY ANALYSIS
Table 5a: Structure of the efficiency frontiers in 82 different univariate sensitivity analyses
Frequency on
Screening
the efficiency
policy
frontiers
Cases in which the screening policy is on the efficiency frontier
33
81
In all cases except when sensitivity for 50-59 years is at lower limit
29
81
In all cases except when sensitivity for 40-49 years is at lower limit
30
80
In all cases except when discounting is 1%, and when sensitivity for 60-69 years is at
lower limit
25
3
Only when discounting is 1%, when sensitivity for 40-49 years is at upper limit and
when Portion of DCIS that progress to preclinical Local stage is at lower limit
26
82
In all cases
27
82
In all cases
15
1
Only when the sojourn time in local stage is at lower limit value
28
81
In all cases except when the sojourn time in local stage is at lower limit value
16
81
In all cases except when the sojourn time in local stage is at upper limit value
Table 6a: Average impact of input parameters at their lower/upper range values on the ICER values for
screening policies 33, 29, 30, 26, 27, 28 and 16. Note that for parameters marked with *, the lower limits of
parameters increased the ICER and the upper limits decreased the ICER.
Parameter
Discounting
Portion of DCIS that progresses to preclinical Local stage*
Recall rate
Relative mortality in regional stage (parameter B)*
Relative mortality in regional stage (parameter A)*
Percent of invasive diagnostics at recall
Cost of mammography exam
Portion of invasive cancers. that are not preceded by DCIS
Portion of clinically detected cancers in local stage
Sojourn time in DCIS stage
Cancer incidence*
Cost of invasive diagnostics
Relative mortality in local stage (parameter A)
Portion of clinically detected cancers in regional stage
Relative mortality in local stage (parameter B)
Sojourn time in regional stage
Cost of non-invasive diagnostics
Sensitivity above 70 years*
QALY (Diagnostic phase)*
Cost of chemotherapy*
Sojourn time in distant stage
Sensitivity for 50-59 years of age*
QALY (Hormonal therapy)
Sensitivity for 40-49 years*
Attendance
Cost of diagnostics for clinically detected cancers*
Sensitivity for 60-69 years of age*
QALY (Chemotherapy)
Cost of radiotherapy*
Cost of surgery
QALY (Distant stage breast cancer )
QALY (Terminal illness)
Cost of hormonal therapy*
QALY (Radiotherapy)
QALY (2m-1year after surgery)
Portion of clinically detected cancers in distant stage
QALY (Surgery)
QALY (Disease free>1year after operation)
Relative mortality in distant stage (parameter B)
Relative mortality in distant stage (parameter A)
Sojourn time in local stage
Input parameter range
1%
5%
90.4%
33.4%
1.4%
16.6%
0.162
0.094
0.862
0.592
4.7%
42.8%
€44
€66
13.3%
70.6%
38.1%
44.0%
3
7
+10%
-10%
€320
€1560
0.221
0.293
44.1%
49.9%
0.125
0.193
0.36
1.08
€47
€154
98.3%
79.2%
0.997
0.653
€13500
€605
0.35
1.04
99.5%
80.9%
0.472
0.991
94.8%
75.5%
60.1%
87.3%
€957
€55
99.7%
81.1%
0.309
0.975
€4630
€2650
€2320
€2900
0.410
0.620
0.004
0.833
€7180
€395
0.486
0.981
0.518
0.994
8.1%
16.1%
0.578
0.995
0.777
0.999
0.680
0.762
0.814
0.838
3
2
ICER range
68%
147%
81%
141%
79%
131%
86%
127%
84%
126%
87%
117%
84%
116%
96%
115%
90%
113%
89%
113%
90%
112%
88%
112%
93%
109%
93%
108%
93%
107%
95%
105%
97%
105%
98%
105%
98%
104%
84%
104%
98%
102%
99%
102%
96%
102%
98%
102%
99%
102%
96%
102%
99%
101%
98%
101%
99%
101%
99%
101%
99%
101%
100%
101%
93%
100%
100%
100%
100%
100%
100%
100%
100%
100%
100%
100%
100%
100%
100%
100%
98%
96%
SECTION A:
POSSIBLE LIFE-COURSES OF WOMEN IN POPULATION WITHOUT SCREENING AND IN POPULATIONS
WITH SCREENING
Population without screening
Most common life course of women in population without screening is healthy life until death. Some women
develop a breast cancer, according to breast cancer incidence. A portion of invasive breast cancers is preceded
by DCIS, which is non-invasive and can spontaneously regress. The remaining breast cancers start as invasive
from the beginning. When the local stage invasive breast cancer has developed, it may progress to regional
stage breast cancer or it may be clinically detected and treated. Likewise, the regional stage breast cancer can
progress to distant stage breast cancer or it may be clinically detected and treated. Women with distant stage
breast cancer are then also diagnosed clinically and treated accordingly.
Death from breast cancer can occur only when women are diagnosed with breast cancer; that is when they are
in clinical local, regional or distant stage. At any given time of their life course, women can die because of other
causes than breast cancer.
Population with screening
The life courses of women in population that is screened is related to life course of population without screening,
except that the DCIS and the preclinical stages of invasive breast cancer can be detected with screening, thus
diagnosing the women with breast cancer earlier in their lifetime. New life course is also the path of false positive
women, which had positive screening examination but no cancer is found at further invasive diagnostic
assessment. Even though that the majority of breast cancers are diagnosed with screening, some breast
cancers are also diagnosed clinically. The breast cancers are diagnosed clinically in women who develop breast
cancer and do not attend the screening, when they have false negative results at their screening or when the
period between screening intervals is long enough to permit the development of the breast cancer. The
treatment and the survival of the clinically detected and screen detected breast cancers is the same.
MODEL PARAMETERS AND TRANSITIONS
Transitions used in the model (1 week cycle length)
Transition from all alive states to state ''death from other causes''= 2.85  10
7
 exp 0.103  age
Transition from ''healthy'' state to states ''preclinical DCIS and preclinical Local stage''
2


from ages 25-59 = 4.3  10 5  exp   51  age   and for
2


2  10


2


ages above 59 = 6.0  10 5  exp   74  age  


2  24 2


(Note: this probability describes the transition to either preclinical DCIS or to preclinical Local stage. The portion
of transitions to either state is then defined by PDCIS1(see below))
Relative stage-specific mortality from breast cancer
A negative exponential function was fitted to stage-specific breast cancer relative mortality, and fitted parameters
distributions were used to describe the distributions of relative mortality at specific times after the diagnosis.
% of women dead because of breast cancer= A  1  exp B  years after diagnosis
Local stage
A (Mean ± St. Dev.)
0.257+0.0184
B (Mean ± St. Dev.)
0.159+0.0174
Regional stage
0.727+0.0687
0.128+0.0171
Distant stage
0.826+0.00595
0.721+0.0210
Clinical stage distribution
Portion of clinically detected cancers in Local/Regional/Distant stages:
Plocal
Pregional
Pdistant
Beta distribution
α
β
440
634
520
586
1-Plocal-Pregional
2.5%
Quantile
38.1%
41.0%
97.5%
Quantile
44.0%
44.1%
47.0%
49.9%
8.1%
12.0%
16.1%
Mean
Transitions between preclinical screen-detectable stages and transitions from preclinical to clinical stages are
then determined by following formulas:
Ppreclinical localclinical local=Plocal
Ppreclinical localpreclinical regional=1-Plocal
Ppreclinical regionalclinical regional=Pregional / (1-Plocal)
Ppreclinical regionalpreclinical distant=1- Pregional / (1-Plocal)
Ppreclinical distantclinical distant=100%
Note: the transition probabilities represent the portion of women, who move between states after stage specific
sojourn time.
Portion of invasive cancers that are not preceded by DCIS:
Beta distribution
α
β
3.87
5.80
PDCIS1
2.5%
Quantile
13.3%
Portion of DCIS that progress to preclinical Local stage (invasive cancer):
Beta distribution
2.5%
α
β
Quantile
PDCIS2
5.92
3.19
33.4%
Mean
40.0%
Mean
65.0%
97.5%
Quantile
70.6%
97.5%
Quantile
90.4%
Sojourn times (years)
Log-normal distribution
=exp of normal distribution with
2.5%
Quantile
Mean
97.5%
Quantile
3
5
7
STDCIS
Mean
5.54
St. Dev.
0.217
STLocal
4.86
0.101
2
2.5
3
STRegional
3.61
0.259
0.36
0.73
1.08
STDistant
3.55
0.277
0.35
0.70
1.04
Screening characteristics:
Attendance
Beta distribution
α
β
27.9
9.32
Recall rate
2.78
36.9
Invasive diagnostics
among recalled women
3
12
2.5%
Quantile
60.1%
75%
97.5%
Quantile
87.3%
1.4%
7%
16.6%
4.7%
20%
42.8%
Mean
Screening sensitivity:
women aged 40-49 years
Beta distribution
α
β
39.1
6.00
women aged 50-59 years
21.5
1.47
80.9%
93.6%
99.5%
women aged 60-69 years
20.0
1.25
81.1%
94.1%
99.7%
women older than 70 years
28.4
2.74
79.2%
91.2%
98.3%
2.5%
Quantile
75.5%
86.7%
97.5%
Quantile
94.8%
Mean
QALY weights and durations of disease/treatment phases [25,26]:
Beta distribution
α
β
0.746
1.85
2.5%
Quantile
0.00367
0.288
97.5%
Quantile
0.833
Mean
Terminal illness
1 month
Distant stage breast cancer
life expectancy
44.3
41.7
0.410
0.515
0.620
Chemotherapy
6 months
3.73
1.47
0.309
0.717
0.975
Radiotherapy
2 months
6.42
1.58
0.486
0.803
0.981
Hormonal therapy
2 years
5.31
1.17
0.472
0.820
0.991
2m-1year after surgery
10 months
5.80
1.07
0.518
0.844
0.994
Surgery
2 months
6.96
1.07
0.578
0.867
0.995
Diagnostic phase
5 weeks
8.82
1.04
0.653
0.895
0.997
Disease free>1year after operation
life expectancy
11.9
0.670
0.777
0.947
0.999
Costs of mammography examination, diagnostic procedures and treatments (Euros (€)) [1]:
Log-normal distribution
=exp of normal distribution with
Mean
St. Dev.
2.5%
Quantile
Mean
97.5%
Quantile
55
Mammography examination
Invasive diagnostic procedures
6.86
0.648
320
1176
1560
Noninvasive diagnostic procedures
4.5
0.596
47
107
154
Diagnostics for clinically detected cancers
5.74
1.19
55
635
957
Surgery
7.85
0.06
2320
2582
2900
Radiotherapy
8.19
0.169
2650
3641
4630
Hormonal therapy
6.61
0.975
395
1191
7180
Chemotherapy
8.04
0.909
605
4680
13500