Original Research Distinct MR Imaging Features of Triple-Negative Breast Cancer with Brain Metastasis Ren-Hua Yeh, MD, Jyh-Cherng Yu, MD, Chi-Hong Chu, MD, Ching-Liang Ho, MD, Hung-Wen Kao, MD, Guo-Shiou Liao, MD, Ho-Wen Chen, MS, Woei-Yau Kao, MD, PhD, Cheng-Ping Yu, MD, Tsu-Yi Chao, MD, PhD, Ming-Shen Dai, MD, PhD From the Division of Hematology/Oncology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan (R-HY, M-SD, C-LH, W-YK); Division of General Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan (C-HC, G-SL, J-CY); Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan (H-WK); Cancer Center, Tri-Service General Hospital, Taipei, Taiwan (H-WC); Department of Pathology, Tri-Service General Hospital, Taipei, Taiwan (C-PY); and Division of Hematology/Oncology, Shuang-Ho Hospital, Taipei Medical University, Taipei, Taiwan (T-YC).
ABSTRACT BACKGROUND
Patients with triple-negative breast cancer (TNBC) are at increased risk of brain metastases (BMs). In this retrospective single-institutional study, we assessed the radiographic features from a cohort of breast cancer (BC) patients with confirmed BM. METHODS
Women diagnosed with BC with BM from January 1, 1996 to May 31, 2012 were identified through institutional databases. Relevant medical records were reviewed to assess patterns of recurrence, treatment, magnetic resonance imaging (MRI) features of BM, and survival after BM. The MRI finding of BM was classified as solid, necrotic, leptomeningeal spread, or mixed type. We assigned the patient into three groups according to histologic subtype of primary BC. RESULTS
In total, 62 patients, median age 53 years (range 20-78), were identified and specific treatment for BM consisted of radiotherapy, surgical resection, and systemic chemotherapy. The initial stage, post-BM survival and overall survival were not significantly different. However, cystic necrotic BMs appeared on MR images were significantly more associated with the TNBC group. CONCLUSION
Patients with BMs from TNBC have distinct MRI features helping the assessment of newly developed BM. A large confirmatory study with correlated histology in this unique patient population will be required.
Introduction Breast cancer (BC) is the second most common primary tumor responsible for the development of brain metastases (BMs).1 The prevalence of central nervous system metastasis from BC is increasing with reported incidence of 10-16%,2,3 attributed to improved systemic therapy for extracranial disease. Clinical behavior of BC and relevant prognosis differs between subtypes.4–6 Patients of BC with BM tend to have poor prognosis, with a median survival of 4-6 months despite optimal treatment. Risk factors reported for BM include younger age, estrogen-receptor (ER)-negative status, HER2/neu oncogene overexpression, poor nuclear differentiation, and presence of nodal metastasis. Patients with triple-negative breast cancers (TNBC), defined by the absence of ER, progesterone receptor (PR) and HER2, are at higher risk of being diagnosed with BM compared with the luminal (either ER or PR positive) or HER2-
474
Copyright
Acceptance: Received June 2, 2013, and in revised form April 1, 2014. Accepted for publication April 26, 2014. Correspondence: Address correspondence to Ming-Shen Dai MD, PhD, No. 325, Sec. 2, Cheng-Gong Road, NeiHu Dist., Taipei, Taiwan. Division of Hematology/Oncology, Department of medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. E-mail: [email protected]. Conflicts of Interest: The authors declare no financial or commercial conflict of interest. J Neuroimaging 2015;25:474-481. DOI: 10.1111/jon.12149
positive subtypes.7 TNBC is characterized by a more aggressive clinical course and higher incidence of earlier development of local/distant recurrence, resulting in dismal outcomes. HER2positive BC patients also have a higher incidence of BM than patients with HER2-negative.8 As anti-Her2 antibody improves systemic disease control, an intracranial sanctuary led to growing incidence of BM. The ER, PR and HER2 expression may differ between the primary and recurrence or distant metastases after initial treatment. Therefore, biopsy of recurrent or metastatic lesions for reassessment of biological features is necessary for subsequent treatment.9 However, brain metastatic lesions are difficult in sampling for histological confirmation. Brain magnetic resonance imaging (MRI) is the modality of choice in detecting and following cerebral neoplasms and to differentiate from other nonmalignant causes. There are very few studies reporting MRI
◦ 2014 by the American Society of Neuroimaging C
Keywords: Breast cancer, triplenegative, brain metastasis, necrotic lesion.
Table 1. Breast Cancer Patients with Brain Metastasis Luminal
Number Initial stage (%) I II III IV Symptomatic BM (%) Diagnosis time to BM median months (range) Survival time after BM median months (range) Overall survival median months
Her2
TNBC
31
19
12
3 (9.7) 12 (38.7) 11 (35.5) 5 (16.1) 24 (77.4) 22 (7-174) 7 (2-34) 35.5
1 (5.3) 13 (68.4) 3 (15.8) 2 (10.5) 14 (73.7) 35 (1-66) 14 (2-34) 46
2 (16.7) 6 (50) 4 (33.3) 0 9 (75) 33 (17-54) 9 (2-25) 38
P value
.392
.526 .533
BM = brain metastasis, TNBC = triple-negative breast cancer.
features of BM from BC in the literature. Clinical treatment strategies for BM are limited such as whole brain irradiation or stereotactic surgery with/without additional systemic therapies, largely depend on the subtype of primary breast tumor. In this study, we aim to retrospectively examine the MRI feature of BM from different subtypes of recurrent BC in order to subclassify the BMs.
Patients and Methods Patients This study was approved by the Institutional Review Board of Tri-Service General Hospital. Women diagnosed with BC with BM from January 1, 1996 to August 31, 2012 were iden-
tified through institutional databases. Patients with secondary parenchymal involvement from contiguous skull or dural-based disease, or any alternative diagnosis for the enhancing brain lesions, such as demyelinating disease or infection, were excluded. In addition, patients were not included in this study if the available clinical and imaging data could not be confidently supported to the diagnosis. Sixty-two patients were considered to have parenchymal BM from BC. Seven of these patients had pathologically proven BC metastasis to the brain with gross total resection. Twenty patients had pathologic sampling from other sites in the body that demonstrated widely disseminated BC metastases. Thirty-five patients treated for BMs only had biopsies of the primary site, but they demonstrated radiographic evidence of widespread systemic metastases in a pattern
Fig 1. Common representative MR imaging features of breast cancer with brain metastasis on contrast-enhanced T1-weighted images: (A) solid-enhancing tumor with perifocal edema, (B) necrotic tumor with thick enhancing wall, (C) (cystic) necrotic tumor with thin enhancing wall, (D) leptomenigeal metastasis, (E) coexistence of solid and necrotic tumors in separated lobes, and (F) coexistence of solid and necrotic tumors in the same lobe.
Yeh et al: TNBC with Cystic Necrotic Brain Metastasis
475
Table 2. MRI Features of Brain Metastasis
Number MRI pattern of BM Solid Cystic-necrotic Thick-necrotic Leptomeningeal spread Mixed Mean number of metastatic lesions (range) Presence of other metastasis (liver/bone/lung/node)
Luminal
Her2
TNBC
31
19
12
24 1 2 1 3 4.3 (1-48) 20
15 0 1 1 2 3.5 (1-53) 17
0 9 2 0 1 5.4 (1-26) 10
P value
*
ABSTRACT BACKGROUND
Patients with triple-negative breast cancer (TNBC) are at increased risk of brain metastases (BMs). In this retrospective single-institutional study, we assessed the radiographic features from a cohort of breast cancer (BC) patients with confirmed BM. METHODS
Women diagnosed with BC with BM from January 1, 1996 to May 31, 2012 were identified through institutional databases. Relevant medical records were reviewed to assess patterns of recurrence, treatment, magnetic resonance imaging (MRI) features of BM, and survival after BM. The MRI finding of BM was classified as solid, necrotic, leptomeningeal spread, or mixed type. We assigned the patient into three groups according to histologic subtype of primary BC. RESULTS
In total, 62 patients, median age 53 years (range 20-78), were identified and specific treatment for BM consisted of radiotherapy, surgical resection, and systemic chemotherapy. The initial stage, post-BM survival and overall survival were not significantly different. However, cystic necrotic BMs appeared on MR images were significantly more associated with the TNBC group. CONCLUSION
Patients with BMs from TNBC have distinct MRI features helping the assessment of newly developed BM. A large confirmatory study with correlated histology in this unique patient population will be required.
Introduction Breast cancer (BC) is the second most common primary tumor responsible for the development of brain metastases (BMs).1 The prevalence of central nervous system metastasis from BC is increasing with reported incidence of 10-16%,2,3 attributed to improved systemic therapy for extracranial disease. Clinical behavior of BC and relevant prognosis differs between subtypes.4–6 Patients of BC with BM tend to have poor prognosis, with a median survival of 4-6 months despite optimal treatment. Risk factors reported for BM include younger age, estrogen-receptor (ER)-negative status, HER2/neu oncogene overexpression, poor nuclear differentiation, and presence of nodal metastasis. Patients with triple-negative breast cancers (TNBC), defined by the absence of ER, progesterone receptor (PR) and HER2, are at higher risk of being diagnosed with BM compared with the luminal (either ER or PR positive) or HER2-
474
Copyright
Acceptance: Received June 2, 2013, and in revised form April 1, 2014. Accepted for publication April 26, 2014. Correspondence: Address correspondence to Ming-Shen Dai MD, PhD, No. 325, Sec. 2, Cheng-Gong Road, NeiHu Dist., Taipei, Taiwan. Division of Hematology/Oncology, Department of medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. E-mail: [email protected]. Conflicts of Interest: The authors declare no financial or commercial conflict of interest. J Neuroimaging 2015;25:474-481. DOI: 10.1111/jon.12149
positive subtypes.7 TNBC is characterized by a more aggressive clinical course and higher incidence of earlier development of local/distant recurrence, resulting in dismal outcomes. HER2positive BC patients also have a higher incidence of BM than patients with HER2-negative.8 As anti-Her2 antibody improves systemic disease control, an intracranial sanctuary led to growing incidence of BM. The ER, PR and HER2 expression may differ between the primary and recurrence or distant metastases after initial treatment. Therefore, biopsy of recurrent or metastatic lesions for reassessment of biological features is necessary for subsequent treatment.9 However, brain metastatic lesions are difficult in sampling for histological confirmation. Brain magnetic resonance imaging (MRI) is the modality of choice in detecting and following cerebral neoplasms and to differentiate from other nonmalignant causes. There are very few studies reporting MRI
◦ 2014 by the American Society of Neuroimaging C
Keywords: Breast cancer, triplenegative, brain metastasis, necrotic lesion.
Table 1. Breast Cancer Patients with Brain Metastasis Luminal
Number Initial stage (%) I II III IV Symptomatic BM (%) Diagnosis time to BM median months (range) Survival time after BM median months (range) Overall survival median months
Her2
TNBC
31
19
12
3 (9.7) 12 (38.7) 11 (35.5) 5 (16.1) 24 (77.4) 22 (7-174) 7 (2-34) 35.5
1 (5.3) 13 (68.4) 3 (15.8) 2 (10.5) 14 (73.7) 35 (1-66) 14 (2-34) 46
2 (16.7) 6 (50) 4 (33.3) 0 9 (75) 33 (17-54) 9 (2-25) 38
P value
.392
.526 .533
BM = brain metastasis, TNBC = triple-negative breast cancer.
features of BM from BC in the literature. Clinical treatment strategies for BM are limited such as whole brain irradiation or stereotactic surgery with/without additional systemic therapies, largely depend on the subtype of primary breast tumor. In this study, we aim to retrospectively examine the MRI feature of BM from different subtypes of recurrent BC in order to subclassify the BMs.
Patients and Methods Patients This study was approved by the Institutional Review Board of Tri-Service General Hospital. Women diagnosed with BC with BM from January 1, 1996 to August 31, 2012 were iden-
tified through institutional databases. Patients with secondary parenchymal involvement from contiguous skull or dural-based disease, or any alternative diagnosis for the enhancing brain lesions, such as demyelinating disease or infection, were excluded. In addition, patients were not included in this study if the available clinical and imaging data could not be confidently supported to the diagnosis. Sixty-two patients were considered to have parenchymal BM from BC. Seven of these patients had pathologically proven BC metastasis to the brain with gross total resection. Twenty patients had pathologic sampling from other sites in the body that demonstrated widely disseminated BC metastases. Thirty-five patients treated for BMs only had biopsies of the primary site, but they demonstrated radiographic evidence of widespread systemic metastases in a pattern
Fig 1. Common representative MR imaging features of breast cancer with brain metastasis on contrast-enhanced T1-weighted images: (A) solid-enhancing tumor with perifocal edema, (B) necrotic tumor with thick enhancing wall, (C) (cystic) necrotic tumor with thin enhancing wall, (D) leptomenigeal metastasis, (E) coexistence of solid and necrotic tumors in separated lobes, and (F) coexistence of solid and necrotic tumors in the same lobe.
Yeh et al: TNBC with Cystic Necrotic Brain Metastasis
475
Table 2. MRI Features of Brain Metastasis
Number MRI pattern of BM Solid Cystic-necrotic Thick-necrotic Leptomeningeal spread Mixed Mean number of metastatic lesions (range) Presence of other metastasis (liver/bone/lung/node)
Luminal
Her2
TNBC
31
19
12
24 1 2 1 3 4.3 (1-48) 20
15 0 1 1 2 3.5 (1-53) 17
0 9 2 0 1 5.4 (1-26) 10
P value
*
