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SPECIAL FEATURE Imaging findings of triple-negative breast cancer MR imaging of triple-negative breast cancer Takayoshi Uematsu Received: 30 August 2010 / Accepted: 23 September 2010 / Published online: 23 December 2010 Ó The Japanese Breast Cancer Society 2010 Abstract Little is known about the MR imaging features of triple-negative breast cancer (TNBC), but TNBC has a worse prognosis because it has no effective therapeutic targets, such as estrogen receptor for endocrine therapy and human epidermal growth factor receptor 2 (HER2) for anti- HER2 therapy. MR findings of a unifocal lesion, mass lesion type, smooth mass margin, rim heterogeneous enhancement, persistent enhancement pattern, and very high signal intensity on T2-weighted images are typical features of breast MR imaging associated with TNBC. Although TNBC can mimic a benign morphology, the early MR imaging recognition of TNBC could assist in both the pretreatment planning and the prognosis, as well as adding to our understanding of the biological behavior of TNBC. Keywords Triple-negative breast cancer Á Breast MRI Introduction Triple-negative breast cancer (TNBC) is defined by a lack of expression of estrogen receptor (ER), progester- one receptor (PR), and human epidermal growth factor receptor 2 (HER2). It is characterized by distinct molecular, histological, and clinical features including a particularly unfavorable prognosis despite increased sensitivity to standard cytotoxic chemotherapy regimens [1]. TNBC is used as a surrogate marker for basal-like breast cancer defined by gene expression profiling [2]. The basal-like subtype characterized by negativity for ER, PR, and HER2, is associated with an aggressive histology, poor prognosis, and unresponsiveness to the usual endocrine therapies, a shorter survival, and BRCA1-related breast cancer [2, 3]. Contrast-enhanced breast MR imaging is known for high sensitivities of 89–100%; however, the specificity is low or intermediate [4]. Breast MR imaging can provide important information not only on the morphology of the lesions but also on the pathology reflected by signal intensity characteristics on T1- and T2-weighted images and on the functional aspects reflected by the temporal and spatial uptake of contrast medium. Therefore, a recent study reported no rationale to criticize the low specificity of breast MR imaging [5]. In addition, a previous study showed that breast cancers with circumscribed mass could be differentiated from benign masses by using internal enhancement and the kinetic pattern of contrast-enhanced breast MR imaging [6]. Few reports exist on the MR imaging characteristics of TNBC [7, 8]; however, several breast MR imaging features can also be used for detecting TNBC. Breast MR imaging can be the most accurate imaging modality for diagnosis of TNBC by showing malignant MR imaging features that may not be identified by using mammography or ultrasonography. Breast MR imaging technique The technical requirements for breast MR imaging are challenging. High temporal and spatial resolutions are necessary although acquisition speed and spatial resolu- tion are diverging demands. Detailed descriptions of the T. Uematsu (&) Breast Imaging and Breast Intervention Section, Department of Clinical Physiology, Shizuoka Cancer Center Hospital, Naga-izumi, Shizuoka 411-8777, Japan e-mail: [email protected] 123 Breast Cancer (2011) 18:161–164 DOI 10.1007/s12282-010-0236-3

MR imaging of triple-negative breast cancer

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SPECIAL FEATURE Imaging findings of triple-negative breast cancer

MR imaging of triple-negative breast cancer

Takayoshi Uematsu

Received: 30 August 2010 / Accepted: 23 September 2010 / Published online: 23 December 2010

� The Japanese Breast Cancer Society 2010

Abstract Little is known about the MR imaging features

of triple-negative breast cancer (TNBC), but TNBC has a

worse prognosis because it has no effective therapeutic

targets, such as estrogen receptor for endocrine therapy and

human epidermal growth factor receptor 2 (HER2) for anti-

HER2 therapy. MR findings of a unifocal lesion, mass

lesion type, smooth mass margin, rim heterogeneous

enhancement, persistent enhancement pattern, and very

high signal intensity on T2-weighted images are typical

features of breast MR imaging associated with TNBC.

Although TNBC can mimic a benign morphology, the early

MR imaging recognition of TNBC could assist in both the

pretreatment planning and the prognosis, as well as adding

to our understanding of the biological behavior of TNBC.

Keywords Triple-negative breast cancer � Breast MRI

Introduction

Triple-negative breast cancer (TNBC) is defined by a

lack of expression of estrogen receptor (ER), progester-

one receptor (PR), and human epidermal growth factor

receptor 2 (HER2). It is characterized by distinct

molecular, histological, and clinical features including a

particularly unfavorable prognosis despite increased

sensitivity to standard cytotoxic chemotherapy regimens

[1]. TNBC is used as a surrogate marker for basal-like

breast cancer defined by gene expression profiling [2].

The basal-like subtype characterized by negativity for

ER, PR, and HER2, is associated with an aggressive

histology, poor prognosis, and unresponsiveness to the

usual endocrine therapies, a shorter survival, and

BRCA1-related breast cancer [2, 3].

Contrast-enhanced breast MR imaging is known for

high sensitivities of 89–100%; however, the specificity is

low or intermediate [4]. Breast MR imaging can provide

important information not only on the morphology of the

lesions but also on the pathology reflected by signal

intensity characteristics on T1- and T2-weighted images

and on the functional aspects reflected by the temporal and

spatial uptake of contrast medium. Therefore, a recent

study reported no rationale to criticize the low specificity of

breast MR imaging [5]. In addition, a previous study

showed that breast cancers with circumscribed mass could

be differentiated from benign masses by using internal

enhancement and the kinetic pattern of contrast-enhanced

breast MR imaging [6]. Few reports exist on the MR

imaging characteristics of TNBC [7, 8]; however, several

breast MR imaging features can also be used for detecting

TNBC. Breast MR imaging can be the most accurate

imaging modality for diagnosis of TNBC by showing

malignant MR imaging features that may not be identified

by using mammography or ultrasonography.

Breast MR imaging technique

The technical requirements for breast MR imaging are

challenging. High temporal and spatial resolutions are

necessary although acquisition speed and spatial resolu-

tion are diverging demands. Detailed descriptions of the

T. Uematsu (&)

Breast Imaging and Breast Intervention Section,

Department of Clinical Physiology,

Shizuoka Cancer Center Hospital, Naga-izumi,

Shizuoka 411-8777, Japan

e-mail: [email protected]

123

Breast Cancer (2011) 18:161–164

DOI 10.1007/s12282-010-0236-3

Page 2: MR imaging of triple-negative breast cancer

technical requirements for breast MR imaging have been

published elsewhere [4, 9–11]. As an example, we present

the clinical breast MR imaging protocol used during the

study period [7]. The breast MR examinations were per-

formed with the patients in the prone position. The

instrument used was a 1.5-T commercially available sys-

tem (Gyroscan Intera; Philips Medical Systems, Best,

Netherlands) with double breast-surface coils. The imag-

ing protocol included a localizing sequence followed by

sagittal fast spin-echo T2-weighted imaging (repetition

time/echo time (TR/TE), 5056/90; echo train length

(ETL), 15; matrix, 158 9 320) with fat suppression

(spectral presaturation inversion recovery, SPIR) of the

affected breast. Other parameters were field-of-view

18 cm, section thickness 4 mm, interslice gaps 0.8 mm.

This examination was followed by a dynamic study of the

affected breast, consisting of serial imaging of a three-

dimensional (3D) sagittal turbo field-echo T1-weighted

sequence (TR/TE 11/5.4, flip angle 20, matrix 143 9 256)

with fat suppression (principle of selective excitation

technique, ProSet). The parameters were field-of-view

18 cm, section thickness 2 mm, slices were interpolated to

1 mm. Gadopentetate dimeglumine (Magnevist; Bayer

Schering Pharma AG, Berlin, Germany) was administered

as a bolus intravenous injection (2 mL/s) at a dose of

0.1 mmol/kg body weight. This was followed by a 20-mL

saline solution flush. For dynamic studies, 1 pre- and 3

post-enhancement scans were acquired. The scan time was

2 min per scan.

MR imaging characteristics of TNBC

Enhancement lesion type

The BI-RADS lexicon [12] describes three types of

enhancing lesions seen on contrast-enhanced breast MR

imaging: first, ‘‘focus/foci’’ defined as a tiny spot

enhancement, less than 5 mm that is too small to allow

further morphologic characterization; second, ‘‘mass’’

defined as a 3D space-occupying lesion that is one process,

usually round, oval, or irregular in shape; and third, ‘‘non-

mass-like enhancement’’ that is not a mass enhancement

and is characterized by distribution and internal enhance-

ment patterns. Previous studies [7, 8] have shown that

TNBC most often presents as mass (Fig. 1) enhancement

and less commonly non-mass-like enhancement.

Mass shape

Triple-negative breast cancer did not tend to have an

irregular mass shape, but this difference was not statisti-

cally significant in contrast to ER?/PR?/HER2- breast

cancer [7]. TNBC tended to have a round, oval, or lobu-

lated mass shape [7, 8]. For mass shape, TNBC tends to

have a benign mass shape (Fig. 1) although mass shape is

not very important to differentiate malignancy from

benignancy.

Mass margin

Uematsu et al. [7] reported that the majority of these

tumors were a mass lesion type on MR images (95%), and

of the 56 mass lesions studied 39% had smooth mass

margins. Dogan et al. [8] also reported that of the 34 mass

lesions studied 38% had smooth mass margins. A smooth

mass margin (Fig. 1) tended to be associated with TNBC.

This is important because a smooth border of a mass is

frequently used as being indicative of a benign lesion.

Schrading and Kuhl [13] reported that familial breast

cancer tended to exhibit smooth mass margins. High-

grade tumors, such as triple-negative and familial breast

cancer, are likely to manifest as benign morphologic

features.

Mass enhancement

Uematsu et al. [7] reported that 80% of TNBC had rim

enhancement, and rim enhancement was associated with

smooth margins of the mass. Dogan et al. [8] reported that

76.5% of TNBC had rim enhancement. Teifke et al. [14]

reported that visible rim enhancement was the most accu-

rate prognostic enhancement criterion for estrogen receptor

status. The results of these studies show that rim

enhancement may be the most useful MR finding for

identifying TNBC.

Kinetic pattern

Uematsu et al. [7] reported that a persistent enhancement

pattern was significantly associated with TNBC. Initially

rapid enhancement and a washout pattern are generally

regarded to be a malignant pattern on breast MR imaging;

however, this may not apply to TNBC. This different

enhancement pattern of TNBC may come from the hetero-

geneity of the TNBC because TNBC showed no homoge-

neous internal enhancement in our study [7]. Schrading and

Kuhl [13] reported a high percentage (33%; 25/76) of

familial breast cancer to exhibit benign kinetic features. The

results of our study and Schrading’s study show that high-

grade breast cancer is therefore likely to manifest as benign

kinetic features. However, Dogan et al. [8] reported that

time–intensity analysis revealed type 3 in 91% of the 44

TNBC studied. This difference may come from the different

populations of these studies and the inter- and intraobserver

variabilities in breast MR imaging interpretation.

162 Breast Cancer (2011) 18:161–164

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Nevertheless, further study is needed to evaluate the time–

intensity curve pattern of TNBC.

Intratumoral very high signal on T2-weighted images

Uematsu et al. [7] reported that intratumoral very high

signal on T2-weighted images was significantly associated

with TNBC. Intratumoral very high signal on T2-weighted

images (Fig. 1) corresponds to necrosis, and necrosis is a

prognostic factor in invasive breast cancer. An area of in-

tratumoral very high signal on T2-weighted images is a

common finding identified in 34–48% of TBNC [7, 8].

Contrast-enhanced breast MR imaging without T2-weighted

images can not reveal the presence of intratumoral necrosis.

Dynamic contrast-enhanced breast MR imaging with

T2-weighted images can increase the specificity of breast

MR imaging.

Unifocal lesion

The frequency depends on the population studied, the

methods used, and the cutoff point separating multifocal/

multicentric lesions from unifocal lesions. Uematsu et al.

[7] showed unifocal lesions to be significantly associated

with TNBC. Unifocal type may be a characteristic of

TNBC.

Conclusion

Unifocal lesion, mass lesion type, smooth mass margin, rim

enhancement, persistent enhancement pattern, and very

high signal intensity on T2-weighted images are typical

features of breast MR imaging associated with TNBC.

Contrast-enhanced breast MR imaging can be the most

Fig. 1 Triple-negative breast

cancer of right breast in

60-year-old woman. a Sagittal

fat-suppressed T2-weighted MR

image shows a mass with a

relatively smooth border with an

area of intratumoral very high

intensity. b Sagittal turbo

field-echo T1-weighted

contrast-enhanced MR image

with fat suppression shows a

rim enhancing mass with a

relatively smooth border.

c Kinetic analysis shows a fast

and persistent enhancement

pattern in the thick rim

enhancement area (L10 and

L12). A necrosis selected as a

region of interest (ROI) (L11)

shows no enhancement

Breast Cancer (2011) 18:161–164 163

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Page 4: MR imaging of triple-negative breast cancer

accurate imaging modality for diagnosis of TNBC by

showing malignant MR imaging features that may not be

identified by using mammography or ultrasonography.

Breast MR imaging can be an effective noninvasive

imaging technique for detecting TNBC. The MR findings

could assist in both the pretreatment planning and the

prognosis, as well as adding to our understanding of the

biological behavior of TNBC.

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