The false-negative rate for screening mammography may be as high as 8% to 10%. Causes of missed breast cancers can relate to a variety of factors, including those related to the patient, technical issues, perception, and interpretation. This article addresses the causes of missed cancers and offers guidelines for reducing the false-negative rate, without unnecessarily increasing the false-positive rate.
Although mammography is the gold standard for the detection of
early breast cancer, according to data from the Breast Cancer
Detection Demonstration Project, the false-negative rate for
screening mammography may be as high as 8% to 10%.1 Since then,
others authors have suggested an even higher rate (up to 25%) of
missed breast cancers on screening mammography.2,3 Studies have
suggested that double reading4-6 or the use of computer-aided
diagnosis7,8 may increase the accuracy of mammographic
interpretation. Double reading of screening mammography has been
found to improve the sensitivity for breast cancer detection by 5%
Causes of missed breast cancers can relate to a variety of
factors, including those related to the patient, technical issues,
perception, and interpretation. In a review of 320 cases of breast
cancer, Bird et al2 found that 24% were missed at screening by one
reader. Of the missed cancers, 61% were visible in retrospect and
not called, and 18% were interpreted incorrectly. Only 5% were
accounted for by technical errors.2 Careful attention to quality
control, positioning, comparison with prior studies, and the
meticulous use of additional views and adjuvant studies are
necessary to minimize the false-negative rate of mammography. This
article will discuss the causes of missed cancers and guidelines
for reducing the false-negative rate.
Inherent breast density can certainly compromise the ability to
detect a mass, particularly a noncalcified, non-distorting lesion.
In the interpretation of the mammogram of a patient with dense
parenchyma, particular attention to any areas of architectural
distortion and careful assessment for faint microcalcifications are
needed. A patient with dense parenchyma, a negative mammogram, and
a palpable mass needs ultrasound for further lesion evaluation.
Other patient factors relate to difficulties in positioning and
visualizing posterior breast tissue. This may occur in patients who
are very tense, but also occurs in patients who have had strokes,
who have shoulder problems, and in those who are otherwise
Lesions that are located in areas that are difficult to image
with mammography are inherently challenging to diagnose. Lesions
located at the chest wall, particularly those high in the upper
inner quadrant near the sternum or in the posterior-inferior aspect
of the breast, are difficult to visualize.
Proper positioning and image contrast are absolute requirements
for mammography. The technologist must adhere to positioning
standards in order to maximize the amount of tissue included on the
films.9 In order to include an area of palpable abnormality on the
images, the examination must be tailored appropriately and the
necessary views must be performed. Palpable areas should be
identified with radiopaque markers, and the radiologist should
verify that any posteriorly located palpable lesion is included in
the field of view.
For densities seen on the mediolateral oblique (MLO) view only,
a mediolateral (ML) view is helpful to determine if the lesion is
real and whether it is located medially or laterally. Lateral
lesions project lower on the ML view than on the MLO view, and
medial lesions show the reverse displacement. Exaggerated
craniocaudal (CC) views are also helpful to demonstrate a
posteriorly located lesion seen on the MLO view only. The use of a
spot compression view alone may be misleading in the assessment of
a density seen on one view only. A true lesion may look less
apparent on spot compression as other overlying tissue is displaced
from it. Additional off-angle projections (i.e., ML or rolled CC
views) should be utilized to complete the evaluation of a possible
The technologist must optimize image contrast and avoid
underpenetrated or overpenetrated images. Proper placement of the
photocell is necessary to achieve correct optical density on the
images. Careful attention to daily processor quality control is
also necessary to optimize contrast.
Two major causes of missed breast cancers reflect radiologist
errors, namely, perception and interpretation problems. In
perception errors, the lesion is included in the field of view and
is evident, yet the radiologist fails to observe it. The lesion may
or may not have subtle features of breast cancer, rendering it less
visible than more obvious lesions.
Types of lesions that are more easily not perceived are small
non-spiculated masses (figure 1), areas of asymmetry and
architectural distortion, or small clusters of faint amorphous
calcifications. Bird et al2 found most cancers were missed because
of perception problems, and the common types of lesions missed were
noncalcified indistinct or spiculated densities. Goergen et al10
found that missed cancers were statistically significantly of lower
density and were seen on only one of two views more often than were
There are several steps that should be taken routinely to avoid
missed perception of a lesion. Films should always be placed as
mirror images, MLOs together and CCs together. The radiologist's
search pattern should include comparing portions of the images side
by side to look for any focal density. A suggested search pattern
emphasizing a mirror image approach is shown in Figure 2. This
search pattern enhances the ability to identify focal asymmetry
density and small masses. The identification of a focal density on
one view should prompt a search in the same arc (measured from the
nipple) on the other view (figure 3). The posterior aspect of the
breast in the retroglandular region is an area sometimes not
observed by the non-expert mammographer, and attention must be
applied to this zone specifically (figure 4).
Architectural distortion may be the only sign of breast cancer
in a dense breast. The parenchyma must be scrutinized for any
disruption of the orientation of the elements or for an area of
focal pulling or tethering of the tissue (figure 5). Architectural
distortion must be further evaluated unless it represents a
documented post-surgical scar.
The observation of microcalcifications optimally requires
careful evaluation of each film with a magnifying glass, as well as
the naked eye. Optimal reading conditions necessitate high
luminance viewboxes with obscuration of extraneous light.
Magnification views should be performed to evaluate questionable
faint microcalcifications and the morphology of observed
Another perception problem that is extremely important in its
impact on patient management is the diagnosis of multicentric
breast cancer. Multicentric breast cancer (two or more or cancers
in more than one quadrant) is a contraindication to breast
conservation therapy. The observation of an obvious finding (benign
or malignant) may cause the "happy eye syndrome," misleading the
radiologist into not looking carefully for other lesions (figure
Contralateral synchronous breast cancer occurs in 0.19% to 2.0%
of patients,11 so careful attention must also be paid to the
opposite breast. When one lesion that is suspicious for cancer is
observed, the next step should be the search for other suspicious
areas in both breasts that would require biopsy (figure 7).
Interpretation errors by the radiologist occur when a lesion
with suspicious features is mischaracterized as a benign or
probably benign lesion. This situation may occur because of lack of
experience, fatigue, or radiologist inattention.12 Other causes,
though, are that the radiologist does not use all the necessary
views to assess the lesion characteristics or that the lesion is
changing slowly and comparison with older examinations was not
When a seemingly circumscribed mass is identified, assessment of
its borders should be made with spot compression. A round mass may
have margins that are indistinct or microlobulated that become
apparent only with spot compression, and these findings warrant
biopsy. Microcalcifications require magnification views in order to
assess their morphology and number accurately. Decisions about the
characteristics of a lesion identified on screening are made based
on diagnostic mammographic images and not the screening views
Decisions about lesion location should not be made without
verification of the position on multiple views. For example, one
should not assume that a lesion overlying the pectoralis muscle in
the superior aspect of the MLO view is a lymph node. If its
features are not that of a node, additional views are performed to
determine its location and significance (figure 8). Ultrasound may
be a helpful adjunct in the evaluation of a posteriorly located
mass seen on one view only.
Cancers that present with subtle signs of carcinoma are most
challenging to diagnose. Such subtle signs include relatively
circumscribed masses, focal asymmetric densities, architectural
distortion, and small groups of punctate or amorphous
calcifications. Well-circumscribed cancers are very uncommon, but
do exist. Swann et al13 found at least a partial halo sign around
25 of 1000 breast cancers. A well-defined mass found on a baseline
mammogram is considered to be probably benign and is followed at an
early interval; increase in size of a non-cystic circumscribed mass
warrants further intervention (figure 9).
Asymmetric densities are frequently present on mammography and
are associated with a relatively low positive predictive value of
malignancy. However, asymmetries that are developing, that are
associated with microcalcifications or architectural distortion, or
that are palpable are more worrisome and are often biopsied.
Invasive lobular carcinoma accounts for approximately 8% to 10% of
breast cancers, and is a type of cancer easily missed. Common
presentations of invasive lobular carcinoma are an asymmetric
density, architectural distortion, or with negative
As more women undergo screening mammography on a routine basis,
the possibility that a slowly changing cancer goes undetected may
increase. The doubling time for breast cancer ranges from 44 to
1869 days.15 Low-grade malignancies may not change to an obvious
degree between annual interval mammograms. Malignant calcifications
have been reported to be stable for as long as 63 months. However,
comparison with older studies 3 or more years before may
demonstrate the change in size of the lesion. A mammographic
abnormality should be judged by its worst features, not its most
benign features. Therefore, a lesion that has suspicious features,
but seems to be stable for 1 or even 2 years, may still need to be
biopsied (figure 10).
Radiologists must make every effort to reduce the false-negative
rate of mammography without unnecessarily increasing the
false-positive rate. Perception and interpretation problems account
for many missed breast cancers. One must pay careful attention to
film review; searching for developing densities, focal asymmetries,
and masses; and perform complete diagnostic evaluation of potential
lesions detected. AR
The author gratefully thanks Ms. Louise Logan for her
preparation of the manuscript.
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