Keywords
interval breast cancer - National Breast Screening Program - screening mammogram
Introduction
The National Health Service Breast Screening Program (NHSBSP) in England defines interval
breast cancers as cancers that develop in women in the interim between two screening
mammograms. In the United Kingdom, this is usually within 3 years from the most recent
screening mammogram. For every 1,000 women screened in the United Kingdom, 8 are diagnosed
with a screen detected breast cancer and 992 women are reported to have normal mammograms.[1] Three out of the 992 women will be diagnosed with an interval breast cancer before
their next screening mammogram.[1] This could manifest symptomatically or be picked up incidentally either by clinical
examination or through opportunistic screening. Out of 100 interval cancers, 80 cancers
are called true interval cancers as they are not seen on previous screening mammogram
and have either developed after or are occult (category 1). Twenty cancers are seen
on the prior mammogram as a subtle finding (category 2) or as a definite abnormality
(category 3).
The NHSBSP recommends that all interval cancers are reviewed as a feedback learning
loop for mammography readers, as a quality improvement tool and to feedback to patients
if they wanted to know whether their cancer was present on the most recent screening
mammogram.[2]
[3]
[4]
In this essay, we are describing the mammographic features of interval cancers and
learning points from such a review undertaken in the North Yorkshire breast screening
program.
Learning Points
Type of Interval Cancer
Most interval cancers are not visible on the initial screening mammogram, and these
category 1 intervals account for nearly 80% of cases.[1] The cancer could have developed in the interim, could be masked previously by the
high-density breast, or could not be included in the mammogram due to its peripheral
location ([Figs. 1],[2],[3]). Interval cancers are generally higher grade and likely to be estrogen receptor
negative in comparison to screen detected cancers.[5]
Fig. 1 Mediolateral oblique (above) and craniocaudal (below) views of the right breast show
BI-RADS C density with a normal mammogram in December 2018 (A, B) and a new 5 cm mass requiring mastectomy and axillary node clearance in April 2021
(C, D). Category 1 interval cancer.
Fig. 2 Left breast mediolateral oblique view (above) and craniocaudal (CC) (below) shows
BI-RADS B density with no focal abnormality on either view in 2019 (A, B). In 2021 (C, D), there is a new mass with calcification best seen in the CC view.
Fig. 3 Magnified view of the new mass with calcification that was a category 1 interval
cancer.
Mass Lesions
Most interval cancers present as mass lesions.[6] When these are small, they can be misinterpreted as benign ([Fig. 4]). If there is a new mass in an incident screen, be cautious and recall especially
if there is a past personal history of breast cancer, or a family history of breast
cancer.
Fig. 4 Prior mammograms from 9 years ago (A, B). New mass with popcorn calcification misinterpreted as calcifying fibroadenoma (C, D). Grade 2 hormone receptor positive, HER 2 negative cancer.
Calcification
The next common abnormality is microcalcification. As many cases of microcalcifications
are benign, these are likely to be misinterpreted as such ([Fig. 5]). When the microcalcifications are seen in dense breasts and mixed with bilateral
benign calcification, they can be difficult to detect or easy to misinterpret. Ductal
calcification could be misinterpreted as vascular calcification ([Fig. 6]).
Fig. 5 Prevalent screen in January 2018 (A, B) shows solitary cluster of pleomorphic calcification seen best in part (A). It was misinterpreted as benign. Patient presented in December 2020 (C, D) with a lump and mass associated with the calcification.
Fig. 6 Good case demonstrating how new branching ductal calcification can be misinterpreted
as vascular calcification as this case was.
Postsurgical Breast
Abnormalities are difficult to detect when there has been prior surgery. It is important
that the surgical scar is included in the mammogram as best as possible to pick up
subtle changes ([Fig. 7]).
Fig. 7 This case demonstrates the importance of a well-positioned mammogram, especially
in prior cancer surgery to show the site of post operative scar. This may have demonstrated
the changing scar and resulted in an earlier pick up. (A–D) are prior mammograms while (E, F) are mammograms when the patient presented with a lump at the site of previous surgery.
Distribution
Small prepectoral and pectoral masses can be mistaken for lymph nodes if not compared
with priors carefully ([Fig. 8]). Tomosynthesis may help characterize the lesion, but it is sometimes difficult
to differentiate benign from suspicious appearance based on imaging alone and the
lesion may require a biopsy. The screening with tomosynthesis or standard mammography
trial suggested that there is a marginal reduction in interval cancer rates when tomosynthesis
is used in screening, but the sample size and the number of interval cancers were
small in this study. Tomosynthesis is currently not used in screening in the United
Kingdom until further evidence emerges.[7]
Fig. 8 Mass on the pectoral muscle. (A, B) A prior mammogram and (C, D) a new mass on the pectoral muscle that was misinterpreted as a lymph node. The patient
presented with a symptomatic lump in the upper inner quadrant 9 months after her false-negative
screening mammogram (E, F).
Lesions close to nipple are particularly difficult to detect and characterize. It
is important to have technically sound mammograms and to compare serial examinations
to detect abnormalities ([Fig. 9]). Subtle increase in density particularly on the craniocaudal view may be a sign
of cancer.
Fig. 9 Mammograms of the left breast from 2015 (A, B), 2018 (C, D) and 2021 (E, F). BI-RADS B breast density. The ill-defined mass seen only on the oblique view in
2018 was misinterpreted as composite; in retrospect the density has subtly increased
on the craniocaudal. This is clearly seen on both views when it got bigger and became
symptomatic in 2021. Category 2 interval cancer.
Do not forget to check for abnormal lymph nodes overlying the pectoral muscle. These
can represent locally advanced breast cancer, lymphoma, or axillary recurrence in
a previous breast cancer patient ([Fig. 10]).
Fig. 10 Mammograms from 2015 (A) and 2018 (B). Changes in the lymph node cannot be appreciated if the image is technically inadequate
and the periphery of the mammogram is not scrutinized. This lady presented 18 months
after a screening mammogram with left axillary mass as seen on ultrasound (C), category 2 interval cancer.
Temporal Evolution
Small changes are best appreciated on reviewing serial mammograms going back several
years and not just the immediate priors ([Figs. 11] and [12]). It is easy to overlook small and subtle abnormalities when compared with the immediate
prior and assume that appearances are stable.
Fig. 11 Temporal evolution. In comparison to 2016 (A, B), there is a subtle increasing asymmetric density in the upper outer quadrant in
2019 (C, D) that was misinterpreted as composite overlap. Four months after the screening mammogram
(E, F), the patient presents with a lump proven to be a cancer.
Fig. 12 Mass seen on mediolateral oblique view can be misinterpreted as composite, as lesion
is subtle on craniocaudal. Review of serial mammograms (A–F) enables better detection.
Technical Recalls
Diagnostic accuracy is enabled by a technically sound mammogram. Sometimes the images
are blurred, the nipple is not in profile or due to inadequate compression, a mass
or asymmetric density looks like composite overlap. The lesion may not be included
if the positioning is inadequate. This highlights the importance of training mammography
technicians to acquire optimal images and for those reading the mammograms to consistently
recall women with suboptimal images unless there is a good reason not to ([Figs. 7] and [13]).
Fig. 13 Mammogram reported as normal in February 2019 (A, B) and presented with lump in May 2019 (C, D). Note that (A) does not include the lower pectoralis muscle as it is not a well-positioned
mammogram. This was a 42 mm G3 node negative hormone receptor positive, Her 2 negative
cancer. Patient had a left wide local excision and sentinel lymph node biopsy then
died of progressive bone metastases in 2021.
Lesions Visible on One View Only
When mammographic abnormalities are small, they can be misinterpreted as composite
overlap of fibroglandular tissue as they are best seen only on one view. Also, lesions
are often only seen on one view in women with breast implants ([Figs. 14] and [15]).
Fig. 14 Breast implants with new mass only seen on one view, in the lower half of the oblique
view (C). Prior mammograms (A) and (B) are normal. Maintain a low threshold for abnormalities seen on 1 view in women with
implants.
Fig. 15 Prior mammogram (A, B) with the back of breast excluded on the craniocaudal (CC) view. A subtle spiculated
density can be seen in the lower half of the oblique view and at the back of the CC
view on the current mammogram (C, D). This was overlooked as the prior CC was technically inadequate with the retromammary
fat not pulled on. Note both CC views are zoomed in to illustrate the density better.
Conclusion
Interval cancers are an integral part of any screening program. Through adherence
to robust quality standards such as regular reviews of false-negative screening, mammograms
and application of the lessons learnt can improve the screening performance.
