The British Journal of Radiology, 76 (2003), 1321

DOI: 10.1259/bjr/80482243

2003 The British Institute of Radiology

Image features of true positive and false negative cancers in

screening mammograms
1

S MEESON, PhD, 1K C YOUNG, PhD, 2M G WALLIS, FRCR, 3J COOKE, MRCP, FRCR, 3A CUMMIN and
M L RAMSDALE, MSc

1
1

National Co-ordinating Centre for the Physics of Mammography, Department of Medical Physics, St. Lukes Wing,
Royal Surrey County Hospital, Guildford GU2 7XX, 2Warwickshire, Solihull & Coventry Breast Screening Centre,
Coventry and Warwickshire Hospital, Stoney Stanton Road, Coventry CV1 4FH, and 3Jarvis Breast Screening Centre,
60 Stoughton Road, Guildford GU1 1LJ, UK

Abstract. The location, tissue background and imaging characteristics of true positive and false negative screens
of breast cancers have been studied. This data can aid decisions in optimizing the display of mammographic
information with the objective of minimizing false negative screens. Screening mammograms for four groups of
women were digitized; those with screen detected cancers, those with false negative interval cancers, and
matched normals for both groups. The optical density (OD) distribution in the main breast region of each
mammogram was determined. The OD in three regions of interest around the cancers was also measured.
Cancer locations were mapped and warped onto a typical image to show their spatial distribution. Where a
cancer was detectable by calcifications alone it had a relatively low probability of being a false negative interval
cancer. The mean OD differences between the cancer and the cancer background region (excluding
calcifications) were approximately a factor of two lower in dense breasts compared with other breast types.
Poorly defined masses that became interval cancers had mean OD differences that were approximately a factor
of 0.1 OD lower than those that were detectable by screening. 22% of false negative cancers were located near
the chest wall edge of the mammograms compared with 10% of the true positives. The results indicate the
importance of effectively displaying information in the lighter areas of the mammogram, corresponding to
glandular tissues, with sufficient contrast for suspicious mammographic details to be detected. Where the mean
OD differences between the cancer and its background region are low, as measured for some poorly defined
masses, there is an increased risk of a false negative interval cancer. Particular attention should be given to the
chest wall area of the film, especially in the lower retroglandular region, during routine screening.

Mammography is generally accepted to be the most

efficient way of screening for breast cancers in women.
Studies have shown that mammography screening reduces
breast cancer mortality rates in women aged 5069 years
[1, 2], and in the UK screening has led to a reduction in
breast cancer mortality [3]. However, it is well documented
that breast screening with mammography as the primary
modality for imaging is not a flawless test [4, 5]. The
incidence of interval cancers for the early years of the UK
screening programme have been reported by some regions
as being somewhat higher than expected [6, 7]. Reviews
of screening mammograms suggest that a considerable
proportion of these interval cancers could have been
detected at screening. Since the prognoses of interval
cancers are likely to be worse than screen detected cancers,
it is important to minimize the number of false negative
screens. As a step towards this, the location, tissue background and imaging characteristics, including optical
density (OD), of true positive and false negative screens
of breast cancers were studied. This data can aid in
optimizing display of mammographic information with the
objective of minimizing false negative screens. The basic
Received 23 April 2002 and in revised form 21 August 2002, accepted
24 September 2002.

Current address for Dr S Meeson: Clinical Physics, Barts and

The London NHS Trust, 56-76 Ashfield Street, The Royal
London Hospital, London E1 1BB, UK.
The British Journal of Radiology, January 2003

quantitative tools necessary for quantifying some important aspects of image quality in clinical mammograms
have been developed and described in earlier work [810].
These make it possible to evaluate quality measures of
individual mammograms using a quantitative rather than
a subjective approach. These tools, and those developed
specifically for this work, were used in conjunction with
the visual gradings of radiologists to determine how
interval cancers compared with screen detected cancers.

Methods
Case selection
Screening mammograms for two groups of women were
selected and digitized. The groups represented women with
true positive screen detected cancers (TPSC), and women
who presented with interval cancers following a false
negative screen (FNIC). Matched normals were selected
for both the screening mammograms of the TPSC and
the FNIC. The case studies involved incident screening
mammograms from breast screening centres where the
standard practice was to use single view mammograms
(mediolateral oblique (MLO) view). 90 cases in each group
were identified and analysed. The TPSC were cancers
positively identified following the assessment of a screening
mammogram and confirmed by pathology. The breast
screening centres were asked to identify women with screen
13

S Meeson, K C Young, M G Wallis et al

detected cancer who had at least one previous screen

where they were judged to be true negative. The FNIC
were cancers diagnosed in the period between the last
screen and the next scheduled screen, following an earlier
negative or benign assessment of a mammogram. The
matched normals were women whose mammograms
showed no signs of cancer and who were asymptomatic
at the time of the scheduled screen. Normals also had a
subsequent screen in which they were judged to be true
negatives. Cases were selected between early 1992 and
1998. The case selection process was randomized to prevent bias. As the smallest group, the FNIC were selected
first. All the FNIC between the study dates were used from
one of the centres. The cases from the second, larger centre
were evenly selected from the cases occurring between the
specified dates. Similarly, the TPSC were selected evenly
from the cases occurring between the study dates. Matched
normals were independently selected for the TPSC and
FNIC groups. The matched normal was the next woman
with a true negative mammogram that was screened on
the same day as the woman in the cancer group, and who
also had a true negative mammogram 3 years later at
a subsequent screen. The method of selecting matched
normals was chosen to ensure that target film density,
imaging system, location and the process of mammogram
review were all as closely matched as possible. A total of
360 case files were assessed.

Imaging systems used by breast screening centres

160 screening mammograms using Sterling Microvision
C (Sterling UK, Stevenage, UK) film with Sterling
Microvision Detail screens from 160 women attending
screening on mobile and static units were collected from
the first screening centre. Mammograms were taken using
either a GE Medical Systems 600 TS Senix (GE Medical
Systems Europe, Paris, France) or a Siemens Mammomat
2 (Siemens plc Medical Engineering, Bracknell, UK)
operated under automatic exposure control (AEC). The
films were processed using a Sterling T6 processor
operating at 34 C on extended cycle using Sterling
chemicals. The films were batch processed at the end of
each day of screening.
206 mammograms using the Fuji UM-MA (HC) film
(Fuji Photo Film (U.K.), London, UK) with Fuji UM fine
screens from 200 women (includes three women with
bilateral breast cancer) attending screening on mobile units
were collected from the second screening centre. Mammograms were taken using a Siemens Mammomat 300 or
Mammomat 2, operated under AEC. The films were processed using a Fuji FPM 3000 processor operating at a
developer temperature of 34 C on extended cycle and using
Photosol chemicals (Photosol Ltd., Basildon, UK). The
films were batch processed at the end of each day of
screening.
At both centres a tube potential of 28 kV was used
for the majority of mammograms. However, 30 kV
was selected for a small number of women with large
breasts, at the discretion of the radiographers. A
molybdenum/molybdenum target/filter combination was
used together with the bucky grid. A target OD of 1.6 for
a 4 cm thickness of polymethylmethacrylate was used and
the correct operation of the AEC checked regularly. The
general practice was to have the AEC chamber positioned
14

at the chest wall for the quality control films and to move
the chamber for the mammograms, at the discretion of the
radiographers.

Mammogram digitization and radiological review

Screening mammograms were digitized using a Lumisys
Lumiscan 150 HR laser scanner (Lumisys, Sunnyvale,
CA) to enable them to be analysed electronically. Each
mammogram was digitized with a pixel size of 210 mm.
The scanners detected signal was digitized into image pixel
values. Grey scale step wedge films, which were produced
with a sensitometer, were digitized with the mammograms
to enable conversion from image pixel value to OD units
[10].
Two expert film readers with considerable experience in
mammography independently reviewed the mammograms.
The mammograms were viewed in low ambient light
conditions on a masked light box normally used for
reviewing mammograms. The mammogram assessments
included using the screening mammograms to grade the
breast composition as either fatty, mixed density or dense.
The cancer locations and outlines on the screening
mammograms were recorded on transparent overlays
for each of the TPSC and FNIC. Cancer details were
also recorded and cross-referenced with the case reports to
confirm cancer type and whether calcifications were
involved. Radiological and assessment information from
screening reports, interval cancer reports and pathology
reports were recorded for each case. This included the
cancer diameter, which was defined as the maximum
dimension of the cancer measured by pathology [11]. The
report data was combined with the results of mammogram
image analysis to form a record in a database for
subsequent analysis.

Image analysis
The image processing software package Aphelion
(Amerinex Applied Imaging, Inc, Northampton, MA)
was used to semi-automatically create regions of interest
(ROIs) representing the pectoral muscle, main breast and
skin edge. Images were filtered to remove calcifications,
film emulsion pick-off and random noise [9, 10]. Three
additional ROIs were manually drawn for each cancer
around the cancer outline, in the central portion of the
cancer avoiding complex edges, and a ring of local
background breast tissue surrounding the cancer. These
ROIs are shown schematically in Figure 1. All ROIs were
subject to image analysis, including measuring the area,
maximum, minimum and mean OD. Bilateral and multifocal cancers were treated separately.
To allow the known positions of the cancers on the
mammograms to be compared, all the cancer centres were
marked on a typical breast image. The typical breast
was an average sized right breast, selected from a sample
of the digitized mammograms. All images of left breasts
were reflected about the vertical axis at the chest wall
position. Each mammogram breast outline was warped
to more closely match that of the typical breast. The
dimensions of each mammogram image were first linearly
scaled to those of the reference or typical breast image. An
affine warping technique [12] using a set of four reference
The British Journal of Radiology, January 2003

Image features of true positive and false negative cancers

Figure 2. Schematic showing the regions of interest used to

assess distribution of cancer locations throughout the breast.
The breast has been divided into five mutually exclusive anatomical regions of interest and one rectangular region of interest
at the chest wall edge of the film.

Figure 1. Oblique view mammogram showing the three regions

of interest selected for the analysis of cancer features.

points (the base of the pectoral muscle at the chest wall,

the outermost position of the pectoral muscle at the top of
the breast image, the nipple and the bottom of the breast
image near the chest wall) was then used to map each
breast outline to that of the reference or typical breast. As
a result, the digitized mammogram images underwent a
combination of rotation, translation and scaling to make
the output image more closely resemble the typical breast.
Finally, the cancer centre locations on the modified
mammogram images were recorded to allow their positions to be plotted on the typical breast image. Visual
checks were made to ensure that the cancer centre marked
on the typical breast image was consistent with that
expected from its location in the original mammogram. To
assess the distribution of cancer centres, the typical breast
was divided into five mutually exclusive ROIs based on
anatomical and radiological features, as shown in
Figure 2. An additional rectangular ROI was used to
determine the number of cancer centres located close to
the chest wall edge of the film, thereby allowing film
quality assurance and breast positioning implications to be
investigated.

Results
The mean ages for the women in each group are
included in Table 1. These are all around the middle of the
screening age range used in the UK NHS Breast Screening
Programme between 1992 and 1998.

Figure 3. Histogram of the mean optical density (OD) in the

main breast regions of all the mammograms used in this study.
(Labels on the mean OD axis represent the mid-points of the
ranges used to sort the data.)

Mean optical density data

Figure 3 shows the distribution of the mean OD in the
main breast regions of all four groups of mammograms
used in this study, with a meanstandard deviation of
1.600.28. The mean OD data is subdivided by cancer
group and breast type in Table 2(a), and for the matched
normal groups in Table 2(b). For the TPSC the mean
OD (meanstandard error in the mean) increases from
1.350.07 for dense breasts to 1.810.05 for fatty
breasts. Whilst the mean ODs for dense breasts in the
two cancer groups are equivalent, the mean OD in FNIC
fatty breasts is lower at 1.640.07 and equivalent to that
for FNIC mixed density breasts. The number and percentage of dense breasts in which FNIC were discovered is
greater than in the TPSC. However, a x2 test comparing
the number of dense breasts to the number of mixed and
fatty breasts generated a p-value of 0.147. For the TPSC

Table 1. Mean age of the women in the four study groups

Mean agestandard error in the mean

FNIC

FNIC normals

TPSC

TPSC normals

58.60.5

57.50.5

59.20.5

56.60.5

FNIC, interval cancers following false negative screen; TPSC, true positive screen detected cancers.

The British Journal of Radiology, January 2003

15

S Meeson, K C Young, M G Wallis et al

Table 2. (a) Mean optical density (OD) in the main breast region of interest (ROI) and local cancer contrast for each cancer group
and breast type
Breast Type

Dense
Mixed
Fatty

FNIC

TPSC

No.

Mean OD in
main breast ROI

Local cancer
contrast

No.

Mean OD in
main breast ROI

Local cancer
contrast

22
47
23

23.9
51.1
25.0

1.420.06
1.620.04
1.640.07

0.130.02
0.290.02
0.280.03

14
52
25

15.4
57.1
27.5

1.350.07
1.560.03
1.810.05

0.150.03
0.300.03
0.360.04

FNIC, interval cancers following false negative screen; TPSC, true positive screen detected cancers.

Table 2. (b) Mean optical density (OD) in the main breast region of interest (ROI) for each matched normal cancer group and
breast type
Breast Type

Dense
Mixed
Fatty

FNIC normals

TPSC normals

No.

Mean OD in
main breast ROI

No.

Mean OD in
main breast ROI

19
51
22

20.7
55.4
23.9

1.400.05
1.640.03
1.710.05

17
66
8

18.7
72.5
8.8

1.470.10
1.630.03
1.750.07

FNIC, interval cancers following false negative screen; TPSC, true positive screen detected cancers.

group and both matched normal groups the mean OD

increases as tissue type changes from dense, to mixed
density, to fatty.
Table 2(a) also contains data on the local cancer
contrast defined as the absolute mean OD difference
between the whole cancer ROI and the cancer background
ROI. This is a measure of the contrast between the cancer
itself and its immediate surrounding background tissue.
For both cancer groups the mean OD differences were
significantly lower in dense breasts, than in mixed density
or fatty breasts. The mean OD differences were comparable in FNIC mixed density and fatty breasts whereas
TPSC fatty breasts had the greatest mean OD difference of
0.360.04. Figure 4 shows that in the majority of
mammograms (88.8%) the mean OD in the whole cancer
ROI is less than the mean OD in the main breast region. It
also shows that the mean OD in the main breast is
correlated with the mean OD in the whole cancer, i.e.
when the mean OD in the main breast is low, so is the

Figure 5. Histogram showing the distribution of mean optical

density (OD) in the cancer background region of interest
(ROI) of all the cancer group mammograms used in this study.
(Labels on the Mean OD axis represent the mid-points of the
ranges used to sort the data.)

mean OD in the cancer. Figure 5 shows the distribution of

the mean OD in the cancer background ROI for all the
cancer group mammograms used in this study. Whilst
most of the cancer background mean ODs lie within the
mid-range of mammogram densities (1.12.0), there are
cancers in both very light and dark parts of the
mammogram.

Cancer masses

Figure 4. The relationship between the mean optical density

(OD) in the main breast region and the mean OD in the whole
cancer region of interest (ROI).

16

Predominant radiological cancer features are listed

for the two cancer groups in Table 3. Data for bilateral
cancers and multifocal cancers are included in this
analysis. For the two cancer groups there were a similar
proportion of masses without calcifications. There were
more FNIC where calcifications were present with masses,
but fewer cases where the predominant cancer features
The British Journal of Radiology, January 2003

Image features of true positive and false negative cancers

Table 3. Predominant radiological features for the two groups
of cancers
Features

Masses
Masses + calcifications
Parenchymal deformity
Calcifications alone

FNIC

TPSC

No.

No.

52
31
2
7

56.5
33.7
2.2
7.6

46
23
0
22

50.5
25.3
0.0
24.2

FNIC, interval cancers following false negative screen; TPSC,

true positive screen detected cancers.

were solely calcifications. The overall group difference had

a p-value of 0.010 (x2 test). For the FNIC and TPSC,
Table 4 and Table 5, respectively, show a detailed breakdown of numbers and OD data for each mass type. Details
about asymmetric densities, parenchymal deformities and
large areas of ductal carcinoma in situ (DCIS) (TPSC
only) have also been included with this data.
For the two cancer groups there are comparable total
numbers of spiculate masses. There are more poorly
defined masses and asymmetric densities in the FNIC
group than in the TPSC group. Excluding the large area
DCIS, the overall group difference had a p-value of 0.109
(x2 test). The mean OD in the cancer centre ROI is smaller
or comparable to the mean OD in the whole cancer ROI
for individual cancers. Whilst the local cancer contrasts for
the spiculate masses in the two cancer groups are generally
comparable, the cancer contrasts for the poorly defined
FNIC masses are of the order of 0.1 OD lower than for
the TPSC masses.

Cancer diameter
The mean cancer diameters, as measured by pathology,
are shown in Table 4 and Table 5. Table 6 shows the

percentage of cancers divided into bands of 5 mm. The

FNIC cancers at the time of diagnosis are generally larger
than the TPSC cancers (group difference had a p-value of
0.010, x2 test). Overall, the mean diameterstandard error
in the mean for FNIC is 21.21.1 compared to 17.01.0
for TPSC.

Invasive lesion types and histological cancer grades

Spiculate and poorly defined were the most
commonly reported mass types in the two cancer
groups. Table 7 lists the invasive lesion type, histological
grade and breast type for these two mass types (histology
data for the false negative cases were collated from the
interval cancer reports). For both cancer groups the
majority of the invasive lesions were ductal carcinoma.
The number of grade I + grade II cancers was compared
with the number of grade III cancers. The greater number
of grade III cancers that were FNIC was more significant
Table 6. Cancer diameter measured by pathology
Cancer diameter
(mm)

FNIC

TPSC

Frequency

Frequency

,5
5 to 10
11 to 15
16 to 20
21 to 25
26 to 30
31 to 35
.35

1
13
12
20
21
14
2
6

1.1
14.6
13.5
22.5
23.6
15.7
2.2
6.7

5
19
23
20
13
3
5
3

5.5
20.9
25.3
22.0
14.3
3.3
5.5
3.3

FNIC, interval cancers following false negative screening; TPSC,

true positive screen detected cancers.

Table 4. Number, mean optical density (OD) data and mean cancer diameter for each interval cancer following false negative screen
(FNIC) mass type. Details regarding asymmetric densities and parenchymal deformities have also been included with this data
FNIC mass type

Number

Mean OD in
cancer centre

Mean OD in
whole cancer

Local cancer
contrast

Mean OD in
main breast ROI

Mean cancer
diameter (mm)

Spiculate
Well defined
Poorly defined
Asymmetric density
Parenchymal deformity

39
2
30
12
2

1.090.06
1.460.19
1.290.08
1.190.09
1.230.22

1.160.06
1.540.22
1.340.08
1.240.08
1.300.21

0.300.03
0.120.05
0.230.02
0.230.04
0.290.11

1.570.05
1.740.37
1.620.05
1.580.05
1.820.21

17.51.1
8.01.0
19.81.8
22.33.8
47.522.5

ROI, region of interest.

Table 5. Number, mean optical density (OD) data and mean cancer diameter for each true positive screen detected cancers (TPSC)
mass type. Details regarding asymmetric densities, parenchymal deformities and large areas of ductal carcinoma in situ (DCIS) have
also been included with this data
TPSC mass type

No.

Mean OD in
cancer centre

Mean OD in
whole cancer

Local cancer
contrast

Mean OD in
main breast ROI

Mean cancer
diameter (mm)

Spiculate
Well defined
Poorly defined
Asymmetric density
Parenchymal deformity
Large area DCIS

42
5
19
5
0
6

1.090.05
1.280.24
1.140.09
1.300.21

1.220.04
1.330.26
1.230.09
1.330.21

0.350.03
0.210.03
0.340.04
0.210.06

1.650.04
1.660.05
1.630.07
1.640.11

16.11.1
12.42.1
14.81.5
14.22.1

1.050.14

1.160.16

0.260.13

1.430.18

44.05.9

ROI, region of interest.

The British Journal of Radiology, January 2003

17

S Meeson, K C Young, M G Wallis et al

Table 7. Invasive lesion type, cancer grade and breast type for poorly defined and spiculate masses
Mass characteristic

FNIC

Invasive lesion
Ductal
Lobular carcinoma
Medullary carcinoma
Mixed
Mucus carcinoma
Tubular carcinoma
Histological grade
I
II
III
Breast type
Dense
Fatty
Mixed

TPSC

Poorly defined

Spiculate

Poorly defined

Spiculate

22
5
1
0
0
1

75.9
17.2
3.4
0.0
0.0
3.4

27
7
0
1
1
2

71.1
18.4
0.0
2.6
2.6
5.3

14
1
1
0
1
0

82.4
5.9
5.9
0.0
5.9
0.0

36
6
0
0
0
0

85.7
14.3
0.0
0.0
0.0
0.0

8
7
12

29.6
25.9
44.4

8
20
11

20.5
51.3
28.2

1
11
3

6.7
73.3
20.0

15
20
3

39.5
52.6
7.9

9
10
11

30.0
33.3
36.7

5
12
22

12.8
30.8
56.4

3
7
9

15.8
36.8
47.4

2
14
26

4.8
33.3
61.9

FNIC, interval cancers following false negative screen; TPSC, true positive screen detected cancers.

Table 8. Invasive lesion type and cancer grade frequencies for comedo and suspicious calcifications
Calcification characteristic

Invasive lesion
Ductal
Lobular carcinoma
Mixed
Tubular carcinoma
Histological grade
I
II
III

FNIC

TPSC

Comedo

Suspicious

Comedo

Suspicious

9
0
0
0

100.0
0.0
0.0
0.0

16
4
3
3

61.5
15.4
11.5
11.5

3
0
0
0

100.0
0.0
0.0
0.0

19
1
0
1

90.5
4.8
0.0
4.8

1
3
5

11.1
33.3
55.6

6
13
6

24.0
52.0
24.0

0
3
0

0.0
100.0
0.0

6
14
2

27.3
63.6
9.1

FNIC, interval cancers following false negative screen; TPSC, true positive screen detected cancers.

for spiculate masses (p-value of 0.021, x2 test) than for

poorly defined masses (p-value of 0.113, x2 test).
Suspicious and comedo were the most commonly
reported calcification types in the two cancer groups.
Table 8 lists the invasive lesion type and histological grade
for these two calcification types. For both cancer groups
the majority of invasive lesions were ductal carcinoma.

Interval cancer lag time

Figure 6 shows the lag time between a false negative
screening mammogram and a cancer becoming symptomatic and being confirmed by mammography (later

Recall rates
The percentages of women recalled for further assessment in the FNIC and matched normal groups following
routine screening are compared in Table 9. This shows
that while 3.3% were recalled from the normal group of
screened women, 16.7% of the false negatives were recalled
for further assessment.
Table 9. Number and percentage of interval cancers following
false negative screen (FNIC) and FNIC matched normal
women who were recalled following routine screening
Group

No. originally recalled

% recalled

FNIC
FNIC normals

15
3

16.7
3.3

18

Figure 6. Chart showing time lag between false negative

screening mammogram and breast cancer being confirmed by
mammography. (Labels on the lag time axis represent the
upper limit of the ranges used to sort the data.)
The British Journal of Radiology, January 2003

Image features of true positive and false negative cancers

Discussion

(b)

(a)

Figure 7. Cancer centre locations shown for both the interval

cancers following false negative screen (a) and true positive
screen detected cancers (b) cases.

confirmed by pathology). The lag time has been divided

into 6-month bands. The majority of the FNIC were
detected in the period 1230 months after the false
negative screening mammogram.

Cancer locations
The cancer centre locations for the FNIC and the TPSC
are shown in Figure 7. There are large numbers of cancer
centres located in the central region (a subsection of the
main breast that represents the majority of dense glandular
tissue) for both cancer groups. There is a cluster of FNIC
at the chest wall edge of the breast image below the
pectoral muscle that are not similarly located in the TPSC
image. Using the regions of interest identified in Figure 2,
the numbers of cancer centres in each region were determined for the two images in Figure 7. Table 10 shows the
results of this analysis. There are similar numbers of
cancer centres in the pectoral muscle and central ROI. A
small percentage of cancers are located in the skin edge
regions of the two images. The main difference is in the
lower retroglandular region of the images. 10% of the
FNIC occur in this region of the breast image while no
TPSC were found in this region (overall group difference
had a p-value of 0.011; x2 test). 22% of the FNIC cancer
centres were found within the chest wall band whereas
10% of the TPSC were found in this region (p-value of
0.020; x2 test).

Table 10. Number of cancer centres that are located in each

region of interest (ROI) for both cancer groups
ROI

Pectoral muscle
Upper retroglandular
Lower retroglandular
Central
Skin edge
Chest wall band

FNIC

TPSC

Frequency

Frequency

4
18
10
61
4
21

4
19
10
63
4
22

3
28
0
65
7
10

3
27
0
63
7
10

FNIC, interval cancers following false negative screen; TPSC,

true positive screen detected cancers.

The British Journal of Radiology, January 2003

For this study, 360 cases were assessed. These comprised

four groups: women with true positive screen detected
cancer; women with false negative interval cancer; and
matched normals for both groups of women. The case
selection process was randomized to prevent bias. The
matched normals were selected to ensure that target
density, imaging system including film type and X-ray set,
location and film review were all as closely matched as
possible.
Both cancer groups had similar numbers of cancer
features that were classified as masses without calcifications. More FNIC than TPSC were classified as masses
with calcifications, but where a cancer could be detected by
calcifications alone it had a relatively low probability of
being a FNIC (p50.010). Similar results were reported in
previous studies [1, 13].
Figure 3 shows that the mean OD in the main breast
region of the MLO view mammograms varied widely from
mammogram to mammogram, with an overall mean of
1.6 OD. These variations in the mean OD can be explained
by the way the AEC functions. The AEC system varies
exposure to achieve the desired OD for only a relatively
small area of the mammogram, i.e. that immediately above
the detector. The mean OD in the main breast ROI will
therefore vary depending upon the distribution of breast
tissue. This contention is supported by similar results
reported in earlier work [8, 9]. The mean OD in the cancer
background ROIs also varied over a wide range of optical
densities, with the majority of cancers being located
against mean background ODs between 1.1 and 2.0.
For the TPSC and the two matched normal groups, the
mean OD in the main breast ROI were related to the
breast tissue type. The mean OD was lowest for the dense
breasts and highest for the fatty breasts. This suggests that
the AECs on the X-ray sets used operated imperfectly,
leading to systematic underexposure for dense breasts.
This may be a factor that reduces the effectiveness of
mammograms in dense breasts. The mean OD in dense
breasts was similar for both cancer groups. FNIC were
more common in dense breasts than TPSC, in agreement
with work relating breast density to interval cancer
occurrence [14]. The local cancer contrast was lower in
the FNIC fatty breasts than in the TPSC fatty breasts, but
equivalent to the FNIC mixed density breasts. It is likely
that identifying cancers in FNIC fatty breasts was made
more difficult by this lower density contrast, accounting
for why FNIC also occur in some types of fatty breasts.
In both cancer groups the local cancer contrast was
approximately a factor of two lower in the dense breasts
than in other types of breast, making visualizing suspicious
breast features more difficult. This lower contrast in dense
breasts is likely to be one factor explaining the difficulty
radiologists have in detecting lesions in this type of breast.
Spiculate masses were the most common feature in both
cancer groups, with comparable local cancer contrast. A
greater number of spiculate masses that became interval
cancers were histological grade III rather than grade I or
II compared with those detected by screening (p50.021). A
poorly defined mass is at increased risk of being a FNIC,
which may be related to these features being more difficult
to locate in screening mammograms. The local cancer
contrast of poorly defined masses that became FNIC were
19

S Meeson, K C Young, M G Wallis et al

approximately 0.1 OD lower than for TPSC, indicating

that lower local contrast may have been the reason they
were not detected by screening. This suggests that a
number of cancers appear in screening mammograms with
features that are at the borderline between being detectable
and not detectable, i.e. poorly defined masses with a low
local contrast. Thus variations in the presentation of image
information that affect local contrast can be expected to
affect cancer detection rates.
The recall rate for the FNIC normal group is based on a
small number of cases, which has a large associated error.
However, the recall rate expressed as a percentage of the
number of women is comparable to the national rate of
3.1% for approximately the mid-point of the study period
[15]. (NB. The national rate has since risen slightly to
3.9% for the period 1998/1999 [16]). Therefore in this
study, five times more women were recalled for further
assessment following their routine screening mammogram
from the false negative group than normal. This may be
related to the false negative group including women who
were considered to have had either benign or minimal
signs of abnormalities. On a retrospective review, many of
the interval cancers occurred in approximately the same
region of the breast that the initial referral investigated.
Recently reported work suggests a number of procedures
that may help when interpreting indeterminate microcalcifications and areas of architectural distortion [17].
In order to investigate cancer locations on false negative
and true positive mammograms, a warping technique was
used to map each screening mammogram to the selected
typical breast image. The use of an affine warping
transformation with manually obtained control points is
sufficient where the aim is to pool the locations of cancer
centres for a group of women. More sophisticated
algorithms [18] have been proposed and developed,
which are more accurate. However, these are designed to
accurately register two mammograms of the same woman
that have been exposed at different times to look for
changes that may suggest abnormalities and changes in the
breast. They will therefore need to be capable of dealing
with variations due to breast compression and positioning.
The distributions of cancer centres for the two cancer
groups are different. While there are similar numbers of
cancer centres in the central and pectoral muscle ROIs this
is not the case elsewhere in the breast. Small numbers of
cancers were found in the skin edge regions of both cancer
location images. Since cancers do appear in this region
there are associated implications for film design and use,
since it is important to effectively display the full extent of
the breast on a mammogram, including the darker parts of
the mammogram at the skin edge [19]. While many cancer
centres are located in the upper retroglandular region,
it is the lower retroglandular region where the greatest
difference was identified. 10% of FNIC were located in the
lower retroglandular region, whereas none of the TPSC
were centred there. Comparing the chest wall band of the
images with the rest of the breast image, 22% of the FNIC,
compared with 10% of the TPSC, were located in the chest
wall band (p50.020). A figure of 10% for TPSC is in line
with the 12% quoted following a study of cancers located
at the posterior edge of the film [20]. Another study has
also suggested that missed lesions are frequently found
in the retroglandular region of the breast [13]. Both
craniocaudal and mediolateral oblique views of the breast
20

were used in that study. The definitions of the breast

locations in that paper were not explicit and therefore may
be different to those used in this study. However, notably
more cancers were located towards the chest wall edge of
the mammogram and behind the central area of dense
glandular tissues in false negative than true positive cancer
groups. In other work, cancer locations have been
recorded for screen detected cancers in the UK [21, 22],
but no comparison was made with false negative interval
cancer locations. In those studies a mean breast was used
as a reference and a sites-of-occurrence map was constructed using a new coordinate system based on the
locations of the pectoral muscle and nipple. The warped
lesion centroids were found to most likely be in the upper
part of the breast. Further direct comparison between
the cancer centroids in the two studies is not a simple
task owing to the different methods of presenting the
data. A novel technique has also been used to record the
geographical distribution of breast cancers [4]. Cancer
locations were recorded using a stylized diagram and a
simple point and click technique. Whilst it did find that
the distribution of false negative and screen detected
cancers differed in the MLO view, and some clustering
observed in this study was also seen in the published maps,
a larger central distribution of cancers was recorded for
both the false negative and true positive cases reported in
our study than in the previous work. Overall, further
investigation is required to determine if the results of this
study are more widespread, but they do suggest that there
is an imbalance in cancer detection in mammograms and
that more attention should be given close to the chest wall
edge of the film, and particularly the lower retroglandular
region, during routine screening.

Conclusions
Results indicate the importance of effectively displaying
information in the lighter areas of mammograms, corresponding to glandular tissues. Mean OD in the main breast
was generally related to breast tissue type, with mean OD
lowest for dense breasts. Local cancer contrast was also
related to breast tissue type. For both cancer groups local
cancer contrast was approximately a factor of two lower in
dense breasts than in other types of breast. When combined, these characteristics understandably make it more
difficult to detect lesions in this type of breast.
Whilst a cancer detected by calcifications alone had a
relatively low probability of being false negative, spiculate
masses were the most common feature in both cancer
groups. Poorly defined masses are at increased risk of
being false negative interval cancers, which may be related
to the features being more difficult to locate since poorly
defined masses that became false negatives had local
cancer contrasts approximately 0.1 OD lower than for true
positives.
However, not all false negatives are necessarily related
to OD. More false negatives were located in the lower
retroglandular region of the mammograms than true positives, a typically more adipose region of the mammogram
than the main breast. This suggests more attention should
be given to this region of the mammogram during routine
screening.
There appears to be further scope to optimize the
presentation of mammographic images. Better contrast
The British Journal of Radiology, January 2003

Image features of true positive and false negative cancers

display, either using the new generation of very high

contrast film/screen systems or through further technological developments such as digital mammography, may
further reduce the incidence of false negative interval
cancers in the UK NHS Breast Screening Programme.

Acknowledgments
The authors would like to thank the clinical and support
staff at the Warwickshire, Solihull & Coventry Breast
Screening Centre and the Jarvis Breast Screening Centre in
Guildford, who helped to identify and locate the cases
used in this study.

References
1. Burrell HC, Sibbering DM, Wilson ARM, Pinder SE,
Evans AJ, Yeoman LJ, et al. Screening interval breast
cancers: mammographic features and prognostic factors.
Radiology 1996;199:8117.
2. Nystrom L, Rutqvist LE, Wall S, Lindgren A, Lindqvist M,
Ryden S, et al. Breast cancer screening with mammography:
overview of Swedish randomised trials. Lancet 1993;341:
9738.
3. Blanks RG, Moss SM, McGahan CE, Quinn MJ, Babb PJ.
Effect of NHS breast screening programme on mortality from
breast cancer in England and Wales, 19908: comparison of
observed with predicted mortality. BMJ 2000;321:6659.
4. Brown M, Eccles C, Wallis MG. Geographical distribution of
breast cancers on the mammogram: an interval cancer
database. Br J Radiol 2001;74:31722.
5. Forrest P. Breast cancer screening: report to the Health
Ministers of England, Wales, Scotland & Northern Ireland.
London: HMSO, 1986.
6. Day N, McCann J, Camilleri-Ferrante C, Britton P, Hurst G,
Cush S, Duffy S. Monitoring interval cancers in breast
screening programmes: the East Anglian experience. Quality
Assurance Management Group of the East Anglian Breast
Screening Programme. J Med Screen 1995;2:1805.
7. Woodman CB, Threlfall AG, Boggis CR, Prior P. Is the three
year breast screening interval too long? Occurrence of interval
cancers in NHS breast screening programmes north western
region. BMJ 1995;310:2246.

The British Journal of Radiology, January 2003

8. Meeson S, Young KC. Quantification of mammographic

image quality in the NHSBSP. NHS Breast Screening
Programme, 1999 (Occasional Report 99/2).
9. Meeson S, Young KC, Ramsdale ML, Wallis MG, Cooke J.
Analysis of optical density and contrast in mammograms.
Br J Radiol 1999;72:6707.
10. Meeson S, Young KC, Rust A, Wallis MG, Cooke J,
Ramsdale ML. Implications of using high contrast mammography X-ray film-screen combinations. Br J Radiol 2001;
74:82535.
11. Vitak B, Olsen KE, Manson JC, Arnesson LG, Stal O.
Tumour characteristics and survival in patients with invasive
interval breast cancer classified according to mammographic
findings at the latest screening: a comparison of true interval
and missed interval cancers. Eur Radiol 1999;9:4609.
12. Russ JC. The image processing handbook (2nd edn). Boca
Ration, FL: CRC Press, Inc., 1995.
13. Bird RE, Wallace TW, Yankaskas BC. Analysis of cancers
missed at screening mammography. Radiology 1992;184:
6137.
14. Mandelson MT, Oestreicher N, Porter PL, White D,
Finder CA, Taplin SH, et al. Breast density as a predictor
of mammographic detection: comparison of interval- and
screen-detected cancers. J Natl Cancer Inst 2000;92:10817.
15. NHS Breast Screening Programme Review 1995. Sheffield:
NHS Breast Screening Programme, 1995.
16. Reducing the risk: Breast Screening Programme 2000.
Sheffield: NHS Breast Screening Programme, 2000.
17. Burrell HC, Evans AJ, Wilson ARM, Pinder SE. False
negative breast screening assessment. What lessons can we
learn? Clin Radiol 2001;56:3858.
18. Sanjay-Gopal S, Chan H-P, Wilson T, Helvie M, Petrick N,
Sahiner B. A regional registration technique for automated
interval change analysis of breast lesions on mammograms.
Med Phys 1999;26:266979.
19. Meeson S, Young KC, Cooke J. Skin edge perception in
mammograms: a comparison of two film screen combinations. Br J Radiol 2000;73:3705.
20. Schmitt EL, Threatt B. Tumor location and detectability in
mammographic screening. AJR 1982;139:7615.
21. Asquith J, Boggis C. Mammographic location of breast
cancer. RAD Magazine 2000;26:212.
22. Caulkin S, Astley S, Asquith J, Boggis C. Sites of occurrence
of malignancies in mammograms. In Karssemeijer N,
Thijssen M, Hedriks J, Erning L, editors. Digital Mammography Nijmegen. Edited by Dordrecht, The Netherlands:
Kluwer Academic Publishers, 1998:27982.

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