Download Interval cancer: a review of cases among patients included in the

Interval cancer: a review of cases among patients included
in the breast cancer screening programme of Galicia
Poster No.:
C-2249
Congress:
ECR 2016
Type:
Scientific Exhibit
Authors:
A. Novo Amado , M. Vázquez Caruncho , L. Graña Lopez , Á.
1
1
1
1
2
Villares Armas , M. Fraga, J. R. Varela Romero , J. Mosquera
2 1
2
Osés, M. A. Sarandeses Portela ; Lugo/ES, A Coruña/ES
Keywords:
Breast, Mammography, Screening, Observer performance, Cancer
DOI:
10.1594/ecr2016/C-2249
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Page 1 of 24
Aims and objectives
Breast cancer still remains both in Spain and in Europe as one of the leading causes of
death among women. It represents a disease that causes a serious social concern and
dismay among the population. It has been estimated that in 2008 about 332,770 new
cases of breast cancer were diagnosed in Europe, which represents 30% of all cancers
in women. [1]
In 2008, 413 deaths were recorded in Galicia from breast cancer, corresponding to
29.30% of women between 50 and 69 years, 54.72% of women aged 70 or older and
15.98% to the group of women under 50 years. [2]
BCSPG invites women aged 50-69 years. A previous breast cancer is the only exclusion
criteria. Two views mammograms are performed on each breast every two years. Images
are read by two independent radiologists with at least ten years of experience reading
screening mammography. The worst result prevails.
If the result is negative, women will receive personalized information by letter and they
will be encouraged to continue in the program, inviting them to repeat the study after two
years. In the case that additional evaluation is required to get the diagnosis, they will be
given an appointment to be diagnosed in a hospital unit.
Although the screening program has succeeded at reducing the mortality from
breast cancer, today its effectiveness begins to be questioned due to overdiagnosis,
overtreatment and the appearance of interval cancers.[4,5]
At that time, the BCSPG rate of stage II or higher was 39.7% in first round, and 29.37%
in successive rounds, higher than the ones established in the European Guidelines
(<30% in the first round, and <25% in successive rounds). Having missed cancers could
contribute to this high rate, so our objective is to review the breast cancers stage II
or higher that appeared in the Breast Cancer Screening Program of Galicia (Spain)
(BCSPG) during the period 2009-2010. [3]
Methods and materials
237,546 women attended the screening program between 2009 and 2010, what
represents the 81% of the invited population. 6045 mammograms were positive. The
Page 2 of 24
breast cancer detection rate was 2, 96/1000 and the detection rate of the test was 41,
8%. [2]
The mammograms of these 212 cases were reviewed and classified as it were interval
cancers.
In a first phase a radiologist reviews the screening mammogram knowing no feature of
the cancer or its localization. At this time the study can be classified as:
•
•
•
Normal/ benign
Uncertain: it may exist minimal changes, hard to perceive or with no specific
features of malignancy or benignity.
Suspicious: there is a lesion suspicious of malignancy
In a second phase the screening mammogram is compared with the one performed at
the previous round. Mammograms were classified as follows:
a. True negative mammograms: The mammogram at the previous round is normal.
b. False-negative mammograms: The mammogram at the previous round showed the
suspicious lesion of cancer.
c. Minimal signs: There were detectable but non-specific signs of cancer at the previous
round.
This procedure was followed by 3 radiologists, all of them with a broad experience in
reading screening mammograms. [5]
Images for this section:
Page 3 of 24
Fig. 1: Chart of selected population included in the Screening Program and the results
of the test obtained.
© Radiology, Programa Gallego de Detección Precoz del Cáncer de Mama de la Xunta
de Galicia - Lugo/ES
Page 4 of 24
Fig. 2: Chart of total of selected women included in the Screening Program between
years 2009 and 2010 included in our study.
© Radiology, Programa Gallego de Detección Precoz del Cáncer de Mama de la Xunta
de Galicia - Lugo/ES
Page 5 of 24
Results
Nine hundred and ninety two breast cancers were detected in the 2009-2010 period; four
hundred and thirteen breast cancers were diagnosed in 2009 (77 in the first round and 336
in successive rounds). Five hundred and seventy nine breast cancers were diagnosed in
2010 (105 cancers in the first round, and 474 in successive rounds. (Figure 3)
The number of breast carcinomas in stage II or higher were 212 (21.4%).
•
•
•
106 cases were classified as true negative mammograms, so the previous
mammograms did not shown any radiological sign of disease in the place
where the cancer finally appeared.
65 women presented minimal signs in the previous round mammograms.
41 cases were classified as false negative recognizable signs of breast
cancer have not been noticed in the previous round.
In order to understand the main causes of missing carcinomas we have reviewed each
case and we have made an analysis of the mammographic imaging findings.
Minimal signs and false negative mammograms were revised to analyze the imaging
findings overlooked in the previous screening round.
A total of 65 studies were considered as minimal changes and 41 were false negatives.
Imaging findings detected in both cases were classified into these categories:
•
•
•
•
•
•
Architectural distortion (31)
Circumscribed mass or poorly circumscribed mass (29)
Radio-opacity (26)
Microcalcifications (10)
Presence of axillary lymphadenopathy (1)
Unclassified (9)
Architectural distortion was the first cause of undetected cancer in both minimal signs
(26, 1%) and false negatives (31, 7 %) with almost a 50% of all the re-reads. For the
minimal sign cases, 14 (21.5%) were pure architectural distortions, and 3 (4, 6%) were
microcalcifications with architectural distortion.
The fifth edition of the Breast Imaging Reporting and Data System (BI-RADS)© defines
architectural distortion as an appearance in which the normal architecture of the breast
is distorted with no definite mass visible. This includes spiculations radiating from a point
and focal retraction or distortion at the edge of the parenchyma.
Page 6 of 24
Detection of architectural distortion is a challenge for the radiologist, even for the most
experienced ones, because it can be subtle and variable in its presentation. Architectural
distortion represents the third most common mammographic appearance of non-palpable
breast cancer.
Fig. 7: False negative. In the screening mammography there is a distortion in the
upper external quadrant of the right breast that was seen in the previous mammogram.
Diagnosis: Lobular carcinoma.
References: Radiology, Programa Gallego de Detección Precoz del Cáncer de Mama
de la Xunta de Galicia - Lugo/ES
A radio-opacity was the next most frequent finding after the architectural distortion and
the presence of a poorly circumscribed mass, accounting for almost 25% of all cases
seen in 19 (46,3%) of false-negative mammograms, and in 7 (10,7%) of minimal signs
mammograms.
A radio-opacity can be unilateral and have the appereance of normal breast tissue. It is
a challenge in a mammogram seen at a first round as it can be interpreted as normal
breast tissue asymmetrically distributed because they often lack of other specific signs
Page 7 of 24
of breast cancer. In some cases, the radio-opacity was seen apparently unchanged with
respect to previous mammograms.
Fig. 8: Minimal signs. Dense breast with radiopacity in the upper external quadrant
of the left breast. In the screening mammogram a mass with architecture distortion is
seen. Diagnosis: Invasive ductal carcinoma
References: Radiology, Programa Gallego de Detección Precoz del Cáncer de Mama
de la Xunta de Galicia - Lugo/ES
Eight minimal sign had microcalcification: 5 cases (5, 6%) were isolated
microcalcifications and 3 cases (4, 61%) had accompanied in architectural distortion. As
for the false negatives mammograms, 5 cases (12, 1%) were pure microcalcifications.
Microcalcifications are also a diagnostic challenge for the radiologists, even for the most
experienced, because they may not have the typical appearance.
Page 8 of 24
Fig. 10: Minimal signs. Round calcifications with regional distribution that were
interpreted as benign. In the screening mammogram polymorphic calcifications with
segmental distribution and a spiculated mass are seen. Diagnosis: Invasive ductal
carcinoma
References: Radiology, Programa Gallego de Detección Precoz del Cáncer de Mama
de la Xunta de Galicia - Lugo/ES
A mass was missed just in 1 case of minimal signs cases (1, 5%) and in 2 cases of falsenegative mammograms (4, 8%).
Page 9 of 24
Fig. 11: False negative. Ill-defined mass in the upper external quadrant of the right
breast. In the screening mammogram the mass had grown. Diagnosis: Invasive lobular
carcinoma.
References: Radiology, Programa Gallego de Detección Precoz del Cáncer de Mama
de la Xunta de Galicia - Lugo/ES
The total of the imaging findings are summarized in the bar codes of the figures 5 and 6.
Stage of the disease at the time of cancer diagnosis is a fundamental point to analyze as
missed cancers are supposed to bare a poorer prognosis.
Stage of breast cancer is important to determine prognosis and treatment. The goal of the
screening is to reduce the rate of late-stage disease, so these cases, which run away from
the detection, are supposed to be in a higher stage at the diagnosis and consequently,
predict a poor prognosis.
th
The American Joint Committee on Cancer staging system 7 edition was used at the
time of classification of the cancers of this series. [7]
Page 10 of 24
All of our cases were women diagnosed of breast cancer with stage II or higher, not being
included the stages 0 to IB.
Most cases were stage 2A: 69 (65.1%) for the true negative cases, 37 (56.9%) for the
minimal signs cases, and 26 (63.4%) for the false negative ones.
Stage 4 was the less frequent, with only 2 (1.9%) cases of true negatives and another 2
(4.9%) for the false negatives, with no cases in the minimal signs group.
There were most 2B and 3C cases within the minimal signs group, but there were no
significant differences between them.
The table 1 and the bar code of the figure 14 represent the stage of the disease at the
time of the diagnosis in each case.
Images for this section:
Fig. 3: Breast cancer detected in the first and successive rounds in the years 2009 and
2010.
Page 11 of 24
© Radiology, Programa Gallego de Detección Precoz del Cáncer de Mama de la Xunta
de Galicia - Lugo/ES
Fig. 4: Classification and proportion of types of interval cancer included in our study
© Radiology, Programa Gallego de Detección Precoz del Cáncer de Mama de la Xunta
de Galicia - Lugo/ES
Page 12 of 24
Fig. 5: Bar code of the imaging findings detected in the re-reading of breast carcinomas
mammograms, classified as minimal changes in comparison with the mammogram of
the previous round.
© Radiology, Programa Gallego de Detección Precoz del Cáncer de Mama de la Xunta
de Galicia - Lugo/ES
Page 13 of 24
Fig. 6: Bar code of the imaging findings detected in the re-reading of breast carcinomas
mammograms, classified as false negative in comparison with the mammogram of the
previous round
© Radiology, Programa Gallego de Detección Precoz del Cáncer de Mama de la Xunta
de Galicia - Lugo/ES
Page 14 of 24
Fig. 7: False negative. In the screening mammography there is a distortion in the
upper external quadrant of the right breast that was seen in the previous mammogram.
Diagnosis: Lobular carcinoma.
© Radiology, Programa Gallego de Detección Precoz del Cáncer de Mama de la Xunta
de Galicia - Lugo/ES
Page 15 of 24
Fig. 8: Minimal signs. Dense breast with radiopacity in the upper external quadrant of
the left breast. In the screening mammogram a mass with architecture distortion is seen.
Diagnosis: Invasive ductal carcinoma
© Radiology, Programa Gallego de Detección Precoz del Cáncer de Mama de la Xunta
de Galicia - Lugo/ES
Page 16 of 24
Fig. 9: Minimal signs. Ill-defined mass in the union of the upper quadrants of the left
breast. In the previous round, a radiopacity is seen at the same site. Diagnosis: Invasive
ductal carcinoma.
© Radiology, Programa Gallego de Detección Precoz del Cáncer de Mama de la Xunta
de Galicia - Lugo/ES
Page 17 of 24
Fig. 10: Minimal signs. Round calcifications with regional distribution that were
interpreted as benign. In the screening mammogram polymorphic calcifications with
segmental distribution and a spiculated mass are seen. Diagnosis: Invasive ductal
carcinoma
© Radiology, Programa Gallego de Detección Precoz del Cáncer de Mama de la Xunta
de Galicia - Lugo/ES
Page 18 of 24
Fig. 11: False negative. Ill-defined mass in the upper external quadrant of the right
breast. In the screening mammogram the mass had grown. Diagnosis: Invasive lobular
carcinoma.
© Radiology, Programa Gallego de Detección Precoz del Cáncer de Mama de la Xunta
de Galicia - Lugo/ES
Page 19 of 24
Fig. 12: Minimal signs. An ill-defined mass in the external upper quadrant of the right
breast was seen at the screening round. In the previous round a radiopacity was seen.
Diagnosis: Invasive ductal carcinoma
© Radiology, Programa Gallego de Detección Precoz del Cáncer de Mama de la Xunta
de Galicia - Lugo/ES
Page 20 of 24
Fig. 13: Minimal signs. In the screening mammogram a spiculated mass is seen (arrow).
In the previous round, a radiopacity is seen. Diagnosis: Lobular carcinoma.
© Radiology, Programa Gallego de Detección Precoz del Cáncer de Mama de la Xunta
de Galicia - Lugo/ES
Table 1
Page 21 of 24
© Radiology, Programa Gallego de Detección Precoz del Cáncer de Mama de la Xunta
de Galicia - Lugo/ES
Fig. 14: Relationship between stage of the disease and missed cancers
© Radiology, Programa Gallego de Detección Precoz del Cáncer de Mama de la Xunta
de Galicia - Lugo/ES
Page 22 of 24
Conclusion
Systematic analysis of missed carcinomas and their classification according to their main
causes is particularly relevant to assess the quality of a screening program.
The rate of II+ in the BCSPG is higher than the established by the European guidelines.
Twenty one percent of cancers diagnosed in the 2009-2010 had a stage II or higher. Half
of these tumours were missed in the previous round, being 19.3% false negative results.
Architectural distortions, radio-opacities, presence of masses and microcalcifications
were the most frequent misinterpreted mammographic signs.
Lack of experience is not an explanation for these results as all radiologists involved in
the BCSPG have more than ten years of experience and each of them reads more than
5000 mammograms per year.
Biopsy of sentinel node implies considering positives some axillas than otherwise would
be negative, especially when OSNA technique is used. On the other hand, it implies a
change in the staging method.
Surprisingly, missed cancers had the same staging that the true negatives, so a few
cancers have a slow growth rate that would not affect prognosis.
In the BCSPG, breast cancer mortality rate has decreased by 18% since its inception
in 1991.[2]
Personal information
References
[1] Globocan 2008. Available from: http://www.iarc.fr/en/publications/pdfs-online/
wcr/2008/index.php
[2] Programa gallego de detección precoz del cáncer de mama (PGDPCM) Resultados
1992-2010. Available from: http://www.sergas.es/Saude-publica/Programa-de-detecci
%C3%B3n-precoz-do-cancro-de-mama
Page 23 of 24
[3] Data were obtained from the database of the PGDPCM, between the years 2009 and
2010.
[4] Luis Apesteguía Cirizaa y Luis Javier Pina Insaustib. Cribado poblacional
de cáncer de mama. Certezas, controversiasy perspectivas de futuro. Radiología.
2014;56(6):479-484.
[5] M.A. Prieto Garcíaa, R. Delgado Sevillano b, C. Baldó Sierrab, E. González Díaz.
Classification and characteristics of interval cancers in the Principality of Asturias's breast
cancer screening program. Radiología. 2013;55(5):408-415
[6] Payne JI, Caines JS, Gallant J, Foley TJ. A review of interval breast cancers diagnosed
among participants of the Nova Scotia Breast Screening Program. Radiology 2013
Jan;266(1):96-103.
[7] American Joint Committee on Cancer. Breast. In: Edge SB, Byrd DR, Compton CC,
et al, eds. AJCC cancer staging manual. 7th ed. New York, NY: Springer, 2010; 347-376
Page 24 of 24