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THE BREAST
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ORIGINAL ARTICLE
a
Breast Imaging Unit, European Institute of Oncology, 435, Ripamonti Street, 20141 Milan, Italy
b
Division of Radiology, DAPI Clinic, 913 Padre Agostinho Street, 80430-050 Curitiba, Brazil
c
Division of Epidemiology and Biostatistics, European Institute of Oncology, 435 Ripamonti Street,
20141 Milan, Italy
d
Division of Senology, European Institute of Oncology, 435 Ripamonti Street, 20141 Milan, Italy
e
Division of Pathology and Laboratory Medicine, European Institute of Oncology, 435, Ripamonti Street,
20141 Milan, Italy
f
Division of Radiology, European Institute of Oncology, 435 Ripamonti Street, 20141 Milan, Italy
g
Istituto di Scienze Radiologiche, Universita
` degli Studi di Milano, 435 Ripamonti Street, 20141 Milan, Italy
Received 12 July 2005; received in revised form 14 February 2006; accepted 17 February 2006
KEYWORDS Summary The aim of this study was to present mammography and ultrasound
Breast cancer; features, and accuracy, in 348 young women (under 35 years old) with breast cancer,
Young women; and to determine whether such features could be correlated with pathological and
Diagnosis; biological factors. We performed a retrospective review of the radiological,
Radiology; pathological and biological features of women under 35 years old with breast
Tumour markers cancer who were seen in our institute between January 2000 and December 2002. A
total of 348 women were analysed. The sensitivity of mammography was 84.9% and
that of ultrasound was 88%. There is a statistically signicant positive correlation
between the high sensitivity of ultrasound and the histology type (P 0:004) as well
as the expression of PgR (P 0:01). Also, there is a correlation between the
sensitivity of mammography and the histology type (P 0:004). Microcalcications
are associated with age (P 0:05) and overexpression of HER2/neu (P 0:007).
Ultrasound may be the appropriate initial imaging test for symptomatic young
women, and mammography may be useful in conrming the features, although there
Corresponding author. Division of Radiology, DAPI Clinic, 913 Padre Agostinho Street, 80430-050 Curitiba, Brazil.
Tel.: +55 41 32341469; fax: +55 41 32503010.
E-mail address: lineiurban@hotmail.com (L.A.B.D. Urban).
0960-9776/$ - see front matter & 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.breast.2006.02.006
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Radiological features and pathologicalbiological correlations in women with breast cancer 745
was no signicant difference in the accuracy of the two tests. Histological and
biological proles may be correlated with imaging sensitivity.
& 2006 Elsevier Ltd. All rights reserved.
6. Ultrasound features: categories 1/2/3 and complete moderate expression) and 410%
category 4. (complete intense expression).
7. Histology: inltrating ductal, other tu-
mours and DCIS.
8. G: grades 1/2 and grade 3. Results
9. VI: absent and present.
10. ER: o10% and X10%. Of the 348 patients under 35 years old with primary
11. PgR: o10% and X10%. breast cancer, data on clinical features were
12. Ki-67: p25% and 425%. available in 256 cases, mammographic features in
13. HER2/neu: p10%/410% (incomplete and 233, ultrasound features in 239, pathological
Figure 1 A 30-year-old woman with a recently discovered palpable mass in the left breast. An oblique mammograms (a)
demonstrated a mass with extremely dense breast tissue and obscured margins at the site of clinical suspicion. The
ultrasound examination (b) revealed irregular, heterogeneous, microlobulated contours, 30-mm in diameter, and a
hypoechoic mass in the upper quadrants. The pathological diagnosis was inltrating ductal carcinoma.
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Radiological features and pathologicalbiological correlations in women with breast cancer 747
Figure 3 A 31-year-old woman with a palpable mass in the left breast. The examination showed a well-dened
hypoechoic mass with an increase in its diameter (initial ultrasound performed at another institution showed a probably
benign mass 6 months before). The pathological diagnosis was mucinous carcinoma.
The statistical analysis of the association be- slightly higher than that reported in the literature,
tween radiological features, age and family history which varies from 1% to 3%.1,3,4,16 Such discordance
is shown in Table 2. There was a signicant may be explained based on the fact that our
statistical correlation (P 0:05) between age and institute is an oncological referral centre, and as
presence of microcalcications. There was also such our series is prone to selection bias.
some correlation between age and the capacity of The usefulness of mammography in women under
ultrasound to classify the lesion as suspicious, but 35 years old is controversial, mainly because of the
this was not signicant (P 0:09). great density of the glandular parenchyma and
The association between the radiological and the radiosensitivity.1,4,17,18,19,20,21 In a study of 577
histological features is also shown in Table 2. There breast cancer cases, Saarenma et al. reported that
was a signicant statistical correlation between the sensitivity of mammography decreases in young
histological type of the tumour and the capacity patients.22 Initial reports described how approxi-
of mammography (Po0:0001) or ultrasound (P mately 60% of breast cancer cases in younger
0:004) to correctly classify the lesions as suspicious. women were not detected through mammo-
The association between biological proles and grams.23,24 However, recent studies reported that
radiological features is shown in Table 3. There was mammography was able to detect as many as 90% of
a signicant statistical correlation (P 0:01) be- the breast cancer cases in women under 35 years
tween the expression of PgR and an ultrasound old, despite 4070% with dense parenchyma. This
result of suspected malignancy. The expression of increase in sensitivity may be due to technical
HER2/neu had a signicant correlation (P 0:0007) improvements in the mammographic equip-
with the presence of microcalcications. There was ment.4,16,19,25
borderline correlation between the expression of In our study, mammograms were dense in 87% of
PgR and the presence of microcalcications the cases (grade 3/4 BI-RADS) and the sensitivity
(P 0:09), between the expression of HER2/neu was 85%. Several hypotheses might account for the
and mammographic density (P 0:09), and be- high percentage of mammographic ndings suggest-
tween tumour grade and ultrasound classication ing malignancy, despite the high density of gland-
of suspected malignancy (P 0:07). ular parenchyma. Firstly, the radiologist might be
inuenced by clinical information (97% were symp-
tomatic) and by ultrasound (88% had suspected
malignancy) features at the moment of reporting
Discussion the mammography. In our institute, when patients
are symptomatic, mammography and ultrasound
The incidence of breast cancer in women under 35 are usually requested together, and it is frequently
years old in our institute was 5.3%. This gure is the same doctor who performs both examinations.
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Radiological features and pathologicalbiological correlations in women with breast cancer 749
Table 1 Histological and biological characteris- number of lesions with microcalcications than
tics of the breast cancer in young women. older women (3135 years).
Ultrasound has been considered the method of
N (%)
choice for symptomatic young women. The higher
Tumor size percentage of glandular tissue and the presence of
o1 cm 42 (16.1) a palpable mass favour the sensitivity of this
12 cm 96 (36.9) method.2628 Recently, Houssami et al. published
25 cm 98 (37.6) a study comparing the sensitivity of mammography
45 cm 24 (9.2) and ultrasound in young symptomatic women, using
Tumor type independent prospective interpretation of the two
Inltrating ductal 275 (79.0) imaging tests. The authors demonstrated that
Inltrating lobular 7 (2.0) ultrasound has a signicantly greater sensitivity
Inltrating ductal+lobular 8 (2.3) than mammography (84 and 76% respectively) in
Mucinous 6 (1.7) women who are 35 years old or younger.29 In our
Medullary 5 (0.1) study, the sensitivity of US was slightly higher than
Papillary 2 (0.5) that of mammography (88.7% versus 84.9%, respec-
Others 15 (4.2)
tively), but this difference was not statistically
DCIS 26 (7.4)
signicant. However, we recognise that our design
LCIS 4 (1.1)
may be prone to some bias, and the accuracy of the
Tumor grade (G) two imaging tests presented by Houssami and
G1 21 (8.5) colleagues may be the more valid estimate based
G2 102 (41.63) on the study design.29
G3 122 (49.8)
The false-negative rate found in the literature
Vascular invasion has been reported in up to 30% of ultrasound
Absent 181 (59.74) procedures.16,19,25,30 This occurs because the dif-
Present 122 (40.26) ferential diagnosis between well-differentiated
ER (%) carcinomas and benign tumours is very difcult to
o10 103 (30.9) obtain, mainly because broadenoma is the most
X10 230 (69.1) common lesion in young women.4,17,31 In our study,
we found a low proportion of benign and probably
PgR (%)
benign reports (8.3%). This may be due to the way
o10 168 (50.3)
X10 166 (49.7) in which our institute is structured. Our radiologists
are dedicated only to breast diagnosis. Another
Ki-67 (%) important factor is the use of high-quality ultra-
p25 159 (49.3) sound equipment.
425 163 (50.7)
The histopathological examination in our study
HER2/neu (%) revealed that almost all tumours in young women
p10 163 (48.5) were invasive, as approximately 70% of the cases
o10 (incomplete moderate) 28 (8.3) were inltrating ductal carcinomas. These ndings
410 (complete moderate) 39 (11.6) are similar to others reported in the litera-
410 (complete intense) 106 (31.5) ture.3,32,33,34 Some series reported an increasing
incidence of medullary carcinomas in younger
women, but this was not present in our study.1,3,31
Carcinomas in situ have a low incidence in this
Secondly, around 42% of the patients had suspect group of patients, being reported in approximately
calcications that were easily visible in the dense 710% of the cases, similar to what was reported in
breast. Finally, in patients with a mass (74%), the our series. This is typical of a non-screened
lesions were very large (average 3 cm), thereby population.2,3,32
facilitating diagnosis. When we compared pathological and radiological
When we analysed the association between features, we observed that the capacity of mam-
mammographic features and age, it came as no mography and ultrasound to indicate suspected
surprise that breasts were denser in the group of malignancy is related to histological types. For
very young women (p30 years old). However, the ductal carcinoma, the mammography and the
mammography showed similar sensitivity in the two ultrasound were able to indicate suspected malig-
groups. This may result from the fact that very nancy in almost all cases. However, it did not occur
young patients had a statistically signicant higher in the group of other tumours (lobular, medullary,
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750 B. Di Nubila et al.
Table 2 Association between radiological features, age, family history and histological types.
2030 years 3135 years No. 11 Inltrating ductal Other (4) DCIS
(1) Scale 1 fat breast; scale 2 scattered broglandular densities; scale 3 heterogeneous breast; and scale 4 dense
breast.
(2) Category 0 need additional imaging evaluation; category 1 negative; category 2 benign nding; category
3 probably benign nding; category 4 suspected abnormality; and category 5 highly suggestive of malignancy.
(3) Category 1 normal; category 2 benign; category 3 probably benign; and category 4 suspected malignancy.
(4) Others tumours inltrating lobular, mucinous, medullary, papillary and other tumours.
mucinous, papillary, and tubular), in which the sound had more sensitivity to enable malignancy to
sensitivity of mammography was low (57%), but be suspected. Although this nding was statistically
that of the ultrasound was high (86%). Carcinoma in signicant in terms of the PgR and grade of tumours
situ has a low sensitivity on mammography and on only, it could have resulted from the fact that less
ultrasound. differentiated tumours show more echographic
Several reports in which young women with features of malignancy. The second point is that
breast cancer have a higher prevalence of adverse the capacity of mammography to indicate sus-
prognostic factors have been published.7,9,18 The pected malignancy is not inuenced by the biolo-
tumours often have a higher grade of vascular gical proles of the tumours. Only overexpression
invasion (4050%), poorer histological grade of HER2/neu was associated with the mammary
(5075%), more lymph node involvement, more density, but it did not inuence the sensitivity of
frequent involvement of the margins, and a more mammography. The nal point is that the micro-
extensive intraductal component.5,6 Furthermore, calcications are associated with less differen-
it has been reported that this group presents with tiated (negative PgR) and highly proliferative
worse biological proles, such as overexpression of (overexpression of HER2/neu) tumours, which
HER-2/neu (3040%), high levels of Ki-67 (6070%), shows that this group of patients may have more
and decreased expression of ER (4050% negative) aggressive tumours. However, it is relevant to
and PgR (5060% negative) compared with groups of mention that there is always a risk of association
older women.2,5,6,32,34,35,36 Our study showed simi- between the described factors, which can inuence
lar results in this group of patients. results, in spite of sample size.
The correlation between radiological features The main limitation of this study was the fact
and biological factors showed some interesting that we did not have access to all radiological and
points. The rst point is that the ability of biological data of the patients, due to the retro-
ultrasound to classify the lesion as suspicious spective nature of this type of work. In only a total
correctly is correlated with biological proles. If of 233 patients were all sets of data available.
the lesions had poor prognostic factors the ultra- However, all patients in the sample were included
Table 3 Association between radiological features and biological prole.
Category 13 5 (8) 21 (12) 6 (5) 20 (16) 14 (12) 11 (9) 23 (13) 4 (6) 16 (18) 7 (8) 17 (12) 9 (10)
Category 4 59 (92) 149 (88) 105 (95) 104 (84) 99 (88) 109 (91) 149 (87) 62 (94) 74 (82) 82 (92) 119 (87) 82 (90)
P 0:48 P 0.01 P 0:53 P 0:17 P 0.07 P 0:67
(1) scale 1 fat breast; scale 2 scattered broglandular densities; scale 3 heterogeneous breast; and scale 4 dense breast.
(2) category 0 need additional imaging evaluation; category 1 negative; category 2 benign nding; category 3 probably benign nding; category 4 suspected abnormality;
and category 5 highly suggestive of malignancy.
(3) category 1 normal; category 2 benign; category 3 probably benign; and category 4 suspected malignancy.
Radiological features and pathologicalbiological correlations in women with breast cancer
751
ARTICLE IN PRESS
752 B. Di Nubila et al.
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