MRI features of Triple-negative breast cancer: our experience.

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1 MRI features of Triple-negative breast cancer: our experience. Poster No.: C-1852 Congress: ECR 2013 Type: Scientific Exhibit Authors: V. Bertani, A. Gualano, V. Londero, A. Dal Col, M. Marcon, P Clauser, C. Zuiani, M. Bazzocchi ; Udine/IT, Udine, Italy/IT Keywords: Decision analysis, MR, Breast, Cancer DOI: /ecr2013/C-1852 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 27

2 Purpose To investigate the appearance of Triple Negative Breast Cancers (TNBCs) on Magnetic Resonance Imaging (MRI). TNBCs are a subgroup of breast tumors which do not express Estrogen Receptor (ER-), Progesteron Receptor (PR-), and Human Epidermal Growth Factor Receptor 2 (HER2-) and represent 10-20% of all breast cancers [1; 2]. This subtype of breast cancer is characterized by high malignancy potential and poor prognosis. In fact, TNBCs are often associated with high histological grade but they can appear like no-suspicious lesions and so their diagnosis often is delayed. [3; 4]. TNBCs are unresponsive to the usual endocrine therapies; therefore, the primary adjuvant therapy for these cancers is chemotherapy [1] and they have a shorter mean time to distant metastatic disease than no-tnbcs. All these conditions contribute to a poor survival rate [4]. On mammography TNBCs are most commonly visible as masses, with or without calcifications [3; 4; 5]. On mammography about 10% (9-11%) of TNBCs remain occult. [3; 4]. Like masses, TNBCs occur both as irregular shape and ill-defined margins that regular shape and circumscribed margins (Fig.1). This subtype of breast cancer presents higher rate of no suspicious mammographic features compared to no-tnbcs lesions. [6; 7] On ultrasound they appear usually like masses, less commonly as architectural distortion [3]. Echo pattern of mass lesions is oftenhypoechoic or markedly hypoechoic [4;5] and shape more commonly is irregular or lobulated [5], with circumscribed margins [3; 5]. On US, TNBCs also present abrupt interface [4; 5], posterior acoustic enhancement or no posterior features and parallel orientation to the skin [3; 4; 5;] (Fig. 2, 3 and 4). On MRI, TNBCs are usually mass-like lesions with oval or lobulated shape and speculated or smooth margins [2; 3; 8; 9]. In these lesions internal enhancement pattern is most commonly characterized by "rim" [2; 3; 8; 9]. It is defined as greater enhancement in the periphery relative to the center of the lesion, in which central area can represent fibrosis or necrosis [10]. Rim enhancement may be the most useful MRI finding for identifying TNBCs and some authors have identified it as an accurate prognostic enhancement criterion for Estrogen Receptor negative status [11]. This subtype of breast cancer presents kinetic pattern suggestive for malignancy with curves that show washout (type III) [2; 3; 9;]. On T2-weighted images they are most commonly hyperintense lesions because of higher necrotic content [2; 10]. Very high intratumoral signal intensity on T2-weighted images is significantly more frequent in masses with a smooth border than in masses with an infiltrative border. Necrosis is a prognostic factor in invasive breast cancer. The presence of moderate to marked central necrosis in tumor decreases Page 2 of 27

3 relapse-free survival and increases mortality in both patients with node-positive disease and patients with node-negative disease [9]. This study was performed to asses MRI appearance of TNBCs. Images for this section: Fig. 1: Triple negative breast cancer in a 57 year-old woman in the right breast (IDC, high grade). Mammogram (magnified craniocaudal, A, and oblique, B, view) shows a lobulated mass with circumscribed margins (arrows). Page 3 of 27

4 Fig. 2: Ultrasound features of triple negative breast cancer in a 65 year-old woman in the right breast (IDC, high grade): an hypoechoic heterogeneus oval mass (A) with illdefined margins and posterior enhancement (arrowheads); this lesion shows moderate vascularization at color Doppler examination (B). Page 4 of 27

5 Fig. 3: Sonographic features of the triple negative breast cancer in a 63 year-old woman in the right breast (IDC, high grade): an homogeneous hypoechoic oval mass with smooth margins, posterior enhancement and no vascularization at color Doppler examination. Page 5 of 27

6 Fig. 4: Sonographic features of the triple negative breast cancer in a 72 year-old woman in the right breast (medullary carcinoma, high grade): an homogeneous hypoechoic oval mass with smooth margins and posterior enhancement(arrowheads). Page 6 of 27

7 Methods and Materials Patients A computerized search of radiologic and pathologic information systems from January 2010 to October 2012 helped identify 45 patients with 47 biopsy-proved TNBCs (two patients had a synchronous bifocal TNBC). Of the 45 patients, 35 patients (36 biopsy-proved TNBCs) underwent dynamic MRI before surgery for locoregional staging. Patients' age of the 35 patients ranged from 41 to 77 years (mean age: 60 years). MR imaging protocol MR imaging was performed using a 1.5 T MR scanner (Magnetom, Avanto Siemens Medical System,Erlagen,Germany) with a dedicated, bilateral, 7-channels surface breast coil and the patient in the prone position. In case of pre-menopausal patients MR was performed regardless of the phase of menstrual cycle in order not to delay surgery. T1weighted (T1w) images were acquired on the axial plane using a 3D fast low-angle shot pulse sequence (FLASH); T2-weighted (T2w) images were acquired on the axial plane using a fast spin-echo short-time inversion recovery sequence (STIR). Imaging acquisition parameters are summarized in Table 1. Gadobenate Dimeglumine (Gd-BOPTA - Multihance, Bracco, Milan, Italy) was administered IV as an automated bolus injection at a dose of 0.1 ml/kg body weight at a flow rate of 2 ml/s, followed by flushing of 20 ml of saline. Serial dynamic images were acquired before injection of contrast agent and five times after the start of injection. After the examination, images underwent post-processing: subtraction of the pre-contrast images from the post-contrast images, multi-planar reconstruction (MPR) and maximum intensity projection (MIP). Curves of the variations time/signal intensity were constructed placing a region of interest (ROI) on detected foci. In patients with MR suspicious findings, a second-look ultrasonography was performed by the same breast radiologist who evaluated breast MR images. Interpretation of MR images MR images were retrospectively reviewed by two experienced breast radiologists in consensus. At the time of reading sessions, readers were aware of the purpose of the study and of the location of the lesion. Each lesion was described according to enhancement morphology (mass-like-ml or non mass-like-nml), shape (round, oval, lobular, irregular) and margins (smooth, Page 7 of 27

8 ill-defined, spiculated) or distribution (focal, ductal, segmental, regional). We also considered signal intensity in T2-weighted Short-Tau-Inversion-Recovery images (T2wSTIR).Internal enhancement pattern, enhancement rate, dynamic curves were also evaluated both for ML-lesions that for NML-lesions. Internal enhancement pattern was classified in homogeneous, heterogeneous and rim for ML-lesions and homogeneous, heterogeneous, clumped or other subtypes for NML-lesions. The evaluation of enhancement rate was based on initial phase (within the first 2 minutes or when the curve starts to change). The evaluation of type of curve was based on the late phase (after 2 minutes or after the change). The enhancement rate was categorized in <50%, between 50% and 100% or >100%. The type of curve was described as persistent (curve type I), plateau (curve type II) or wash-out (curve type III). Data analysis We analyzed characteristics of TNBCs on MRI using proportions. Images for this section: Table 1 Page 8 of 27

9 Results Of 35 patients, 4 (11.4%) presented familiar history for breast cancer, 6 patients (17.1%) had previous personal history of breast cancer and 2 patient (5.7%) showed other synchronous controlateral breast carcinoma with ER+/PR+/HER- immunophenotype. Furthermore, 1 patient (2.9%) had previous personal history of Hodgkin's lymphoma treated with radiotherapy. Of the 36 TNBCs, 13 (36.1%) were symptomatic, showing palpable nodules (11 patients, 30.5%) or carcinomatous mastitis (2 patients, 5.6%). Clinical history of 35 patients underwent MRI and clinical presentation of 36 TNBCs are showed respectively in Tables 2 and 3. About histological diagnosis of the 36 carcinomas, 28(77.9%)were Invasive Ductal Carcinomas (IDC), 3 (8.3%) were medullary carcinomas, 2(5.5%) were Ductal In Situ Carcinoma (DCIS), 1 (2.8%) was Invasive Lobular Carcinoma (ILC) and 2 lesions (5.5%) showed other histological subtypes (adenoid cystic carcinoma and metaplastic carcinoma) Histological patterns of TNBCs are summarized in Table 4. About the histological grade of all lesions, 24/36 (66.7%) were high grade carcinomas, 9/36 (25.0%) moderate grade carcinomas, 2/36 (5.6%) low grade carcinomas and one lesion (2.7%) was a metaplastic carcinoma. These data are reported in Table 5 Of all lesions, only one was not visible on MRI.Of the 35 MRI-positive lesions, 32 (91.4%) were ML and 3 (8.6%) were NML. Of ML lesions, 15/32 (46.9%) showed oval shape, 8/32 (25.0%) irregular shape, 6/32 (18.7%) lobular shape and 3/32 (9.4%) round shape. Margins were ill-defined in 15/32 (46.9%), smooth in 9/32 (28.1%) and spiculated in 8/32 (25.0%). Internal enhancement was represented by rim enhancement in 13/32 lesions (40.6%), heterogeneous enhancement in 11/32 lesions (34.4%) and homogeneous enhancement in 8/32 lesions (25.0%). High signal intensity was identified on T2w-STIR images in 24/32 lesions (75.0%) (Fig. 5, 6, 7 and 8) MRI morphological features and internal enhancement of ML-lesions are reported in Table 6. Page 9 of 27

10 NML lesions showed segmental distribution in 2 cases and regional distribution in the remaining case with clumped enhancement in each one. (Fig. 9 and 10) MRI distribution and internal enhancement of NML-lesions are summarized in Table 7. Of the 35 MRI-positive lesions, it was not possible to evaluate enhancement rate and dynamic curve in 4 lesions (2 ML and 2 NML) because of the difficult to place ROI in areas of enhancement. In the two cases of ML, one lesion had rim enhancement with thin margins, (Fig. 11) the other one lesion was in a deep localization, near to limits of FOV (field of view) (Fig.12 and 13). In the remaining 31 lesions enhancement rate was >100% in 22 (71.0%), between % in 8 (25.8%) and <50% in one lesion (3.2%). Dynamic curve showed wash-out in 13/31 lesions (41.9%), plateau in 13/31 lesions (41.9%) or persistent enhancement in 5/31 lesions (16.2%) Kinetic patterns of TNBCs are showed in Table 8. Images for this section: Page 10 of 27

11 Table 2 Table 3 Page 11 of 27

12 Table 4 Page 12 of 27

13 Table 5 Page 13 of 27

14 Fig. 5: MRI appearance of a triple negative breast cancer in a 41 year-old woman in the left breast (medullary carcinoma, high grade): axial pre-contrast (A) and early enhanced 3D T1-weighted images (B) with early subtraction (C) showing a mass-like lesion with homogeneous, rapid (type III of kinetic curve) and strong (210%) enhancement rate; this lesion presents smooth margins and oval shape (arrow). It appears hyperintense in axial STIR T2-weighted image (arrowhead, D). Page 14 of 27

15 Fig. 6: MRI appearance of the triple negative breast cancer in a 44 year-old woman in the right breast (IDC, high grade): axial pre-contrast (A) and early enhanced 3D T1-weighted images (B) with early subtraction (C) showing a mass-like lesion with homogeneous, rapid (type III of kinetic curve) and moderate (99%) enhancement rate; this lesion presents smooth margins and oval shape (arrow). It has hyperintense signal in axial STIR T2-weighted image (D). Page 15 of 27

16 Fig. 7: MRI appearance of the triple negative breast cancer in a 63 year-old woman in the left breast (IDC, moderate grade): axial pre-contrast (A) and early enhanced 3D T1-weighted images (B) with early subtraction (C) showing a mass-like lesion with homogeneous, rapid (type III of kinetic curve) and strong (127%) enhancement rate; this lesion presents smooth margins and lobular shape (arrow). It has hyperintense signal in axial STIR T2-weighted image (arrowhead, D). Page 16 of 27

17 Fig. 8: MRI appearance of the triple negative breast cancer in a 72 year-old woman with a palpable nodule in the right breast (IDC, moderate grade): axial pre-contrast (A) and early enhanced 3D T1-weighted images (B) with early subtraction (C) showing a mass-like lesion with rim enhancement; the kinetic curve of the lesion shows plateau (II) and moderate (89%) enhancement rate. The morphological features are smooth margins and irregular shape (arrow). It has central hyperintense signal in axial STIR T2-weighted image (arrowhead, D). Page 17 of 27

18 Table 6 Page 18 of 27

19 Fig. 9: MRI appearance of the triple negative breast cancer in a 64 year-old woman in the left breast (ILC, moderate grade): axial pre-contrast 3D T1-weighted image (A) with early subtraction after contrast injection (B) showing a NML lesion with heterogeneous enhancement and regional distribution; the cancer shows strong (104%) enhancement rate and kinetic curve with plateau (II). Page 19 of 27

20 Fig. 10: The lesion shown in Fig. 9 occurs as diffuse, asymmetric, hyperintense signal in the left breast in axial STIR T2-weighted image. Page 20 of 27

21 Table 7 Page 21 of 27

22 Fig. 11: MRI appearance of the triple negative breast cancer in a 47 year-old woman in the right breast (DCIS, high grade): axial pre-contrast (A) 3D T1-weighted images (B) with early subtraction after contrast injection (C) showing a mass-like lesion with rim enhancement, ill-defined margins and oval shape (arrow). It has central hyperintense signal in axial STIR T2-weighted image (D). It was not possible to evaluate enhancement rate and kinetic curve because of thinness of rim enhancement. Page 22 of 27

23 Fig. 12: MRI appearance of the triple negative breast cancer in a 48 year-old woman with palpable nodule in the left breast (IDC, high grade): axial pre-contrast 3D T1-weighted images (A) with early subtraction after contrast injection (B) and detail (C) showing a ML lesion with rim enhancement, smooth margins and oval shape (arrows). It was not possible to evaluate enhancement rate and kinetic curve because of its deep localization. Page 23 of 27

24 Fig. 13: The lesion shown in Fig.12 presents heterogeneous, hyperintense signal in axial STIR T2-weighted image (arrow). The left breast appears smaller than the controlateral, with thickening of skin and diffuse hyperintense signal (arrowheads). These signs are related to carcinomatous mastitis. Page 24 of 27

25 Table 8 Page 25 of 27

26 Conclusion In MRI the morphology of TNBCs often did not have suspicious features. Enhancement rate >100%, rim enhancement and dynamic curves with wash-out or plateau in our study were more suggestive for malignancy than shape and margins. So, the role of MRI could be to identify into the group of uncertain cases, the lesions that must undergo to percutaneous biopsy. References 1. Irvin et al. What is triple negative breast cancer? European Journal of Cancer (2008) 44: Youk et al. Triple negative invasive breast cancer on dynamic contrastenhanced and diffusion-weighted MR imaging: comparison with other breast cancer subtypes. European Radiology (2012) 22: Dogan et al. Multimodality imaging of triple receptor-negative tumors with mammography, ultrasound and MRI. American Journal of Roentgenology (2010) 194: Krizmanich-Conniff et al. Triple receptor-negative breast cancer: imaging and clinical characteristics. American Journal of Roentgenology (2012) 198: Ko et al. Triple-negative breast cancer: correlation between imaging and pathological findings. Eur Radiol (2010) 20: Kojima et al. Mammography and ultrasound features of TNBC. Breast Cancer (2011) 18: Yang et al. Mammographic features of triple receptor-negative primary breast cancers in young premenopausal women. Breast Cancer Research and Treatment (2008) 111: Uematsu. MR imaging of triple-negative breast cancer. Breast Cancer (2011) 18: Uematsu et al. Triple-negative breast cancer: correlation between MR imaging and pathologic findings. Radiology (2009) 250: Kobayashi et al. Two different types of ring-like enhancement on dynamic MR imaging in breast cancer: correlation with the histopathologic findings. Journal of Magnetic Resonance Imaging (2008) 28: Teifke et al. Dynamic MR imaging of breast lesions: correlation with microvessel distribution pattern and histologic characteristics of prognosis. Radiology (2006) 239: Page 26 of 27

27 Personal Information Page 27 of 27

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