Breast cancer with brain metastases: current treatment options

Breast cancer is the main cause of brain metastases in women. The incidence of brain metastases in breast cancer continues to increase, which is mainly associated with improved systemic therapy, which ensures the control of extracranial metastases and an increase in survival. The management brain metastases of breast cancer remain a challenge, despite the constant improvement of local and systemic therapies. This review of the scientific literature presents the latest data from clinical trials of local and systemic treatment of patients with brain metastatic of breast cancer.

P13.16 Metastatic potential of systemic glioblastoma stem cell lines in vivo

BACKGROUND Despite aggressive tumor behavior, extracranial metastases rarely develop in glioblastoma (GBM) patients. Two potential explanations have been suggested: 1) The blood-brain-barrier functions as a physical barrier that prevents the dissemination of GBM cells out of the central nervous system (CNS) or 2) that extracranial metastasis do occur, but the patients die before extracranial metastases manifest themselves. The first theory has been questioned based on the fact that circulating tumor cells (CTC) were found in blood samples of GBM patients without systemic metastases. To date it has not been proven if CTCs are able to reenter the brain and to what extent they are able to form systemic extracranial metastatic lesions. Therefore, the current study aimed at analyzing the dissemination patterns and the underlying mechanisms associated with the ability of GBM CTCs to form extracranial metastases. MATERIAL AND METHODS Five highly characterized human GBM stem cell (GSC) lines (P3, BG5, BG7, GG6, GG16), displaying GBM CNV patterns, were intracranially implanted in a first cohort, then transduced with a lentiviral Firefly Luciferase-eGFP vector and injected into the left cardiac ventricle of NOD/SCID mice in a second cohort. Mice were observed closely and tumor burden was assessed using in vivo as well as ex vivo bioluminescence imaging, MRI and PET. Mice were euthanized when the objective endpoint criteria (tumor burden) was met, then organs were harvested and fixed for further analysis. RESULTS First, a detailed characterization of the GSC line invasion patterns were assessed when grown as orthotopic xenografts in vivo dividing them into three categories: 1) Highly invasive without apparent angiogenesis (BG5) 2) Invasive with perivascular infiltration and angiogenesis (P3, BG7 and GG16) and 3) Angiogenic and highly circumscribed (GG6). Following intracardial injection, (7 out of 8) P3 animals developed extracranial and intracranial tumors with a distinctive pattern. Brain, adrenal gland, ovary and liver were amongst the organs most susceptible for tumor growth in the P3 group. For the BG5 and BG7 cell lines, no metastases were observed whereas only 1 animal out of 10 developed metastases in both groups GG16 and GG6. CONCLUSION Only one out of 5 GSC lines exhibited a strong metastatic potential when injected into the left cardiac ventricle. Compared to other tumors which exhibit a strong metastatic potential from the circulation, GSC lines do only to a very limited extent show this potential reflecting observations made in the clinic.

RNA Sequence Profiling Reveals Unique Immune and Metabolic Features of Breast Cancer Brain Metastases

There is an urgent need to improve our understanding of breast cancer brain metastases (BCBMs). Thus, we obtained transcriptome data of BCBMs, primary breast cancers (BCs), and extracranial metastases (BCEMs) from the Gene Expression Omnibus (GEO) database, including GSE43837, GSE14017, and GSE14018, for immune and metabolic analysis. Firstly, we performed immune and metabolic analysis on BCBMs and primary breast cancers of GSE43837 using RNA sequence. We identified significant immunosuppression and gene signatures associated with immune infiltration in BCBMs; the lower the expression of the signatures, the worse the prognosis of breast cancer patients in the Kaplan–Meier (KM) plotter [Breast cancer] database. We also identified increased oxidative phosphorylation (OXPHOS) utilization in BCBMs compared with BCs and gene signatures associated with increased OXPHOS utilization in BCBMs; the higher the expression of the signatures, the worse the prognosis of breast cancer patients in the KM plotter [Breast cancer] database, which can predict the prognosis of breast cancer patients better, as it can also predict the prognosis of patients with different breast cancer subtypes. In addition, we performed immune and metabolic analysis on BCBMs and extracranial metastases of GSE14017 and GSE14018 using RNA sequence. Compared with extracranial metastases, we identified more significant immunosuppression but no difference in OXPHOS utilization in BCBMs, which may be because OXPHOS was also involved in extracranial metastases. We have proven that OXPHOS was functionally significant in metastasis in vitro assays. Oligomycin, an OXPHOS inhibitor, substantially attenuated the migration and invasion potential of breast cancer cells. Our study provides new insights into the pathogenesis of BCBMs.SignificanceOur study reports the most comprehensive gene expression analysis of BCBMs, BCs and extracranial metastases to date. We identified immunosuppression and OXPHOS enrichment in BCBMs compared with BCs, which provide new insights into the pathogenesis of BCBMs and will facilitate the development of new therapeutic strategies for patients with BCBMs.

SURG-05. Neurosurgery for brain metastases from non-small cell lung cancer: survival outcome and prognostic factors

Background Surgery is an important approach to treat non-small cell lung cancer (NSCLC) brain metastases (BM). Here, we analyzed the survival outcome and prognostic factors for patients with NSCLC after BM resection. Methods The Surveillance Epidemiology and End Results (SEER) database was employed to address the incidence of BM from NSCLC and the current prognosis at population level. 674 contemporaneous NSCLC patients received BM resection at Sun Yat-sen University Cancer Center (SYSUCC) were used for survival comparison and Cox proportional hazards model was applied for identifying prognostic factors. Results 60,436 NSCLC patients diagnosed between 2010 to 2017 were enrolled from SEER database. Among them, 8,708 (14.4%) BM were identified at primary NSCLC diagnosis (synchronous BM, SBM). Median overall survival (OS) of SBM was 6 months with 1-, and 3-year survival percentages of 30.3% and 9.8%, respectively. Furthermore, the survival of BM patients without extracranial metastasis is significantly longer than those with extracranial metastases (median OS: 10 versus 5 months, P<0.001). 225 SBM (cohort A) and 449 BM with treatment history on primary NSCLC (cohort B) were collected from SYSUCC. In cohort A, 86 BM with extracranial metastases were found (38.2%) and the median OS was significantly shorter than those without extracranial metastases (15.2 versus 23.7 months, P<0.001). In cohort B, 255 cases with extracranial metastases were found (56.8%) and their prognosis was also worse than cases without extracranial metastases (median OS: 18.3 versus 22.1 months, P=0.002). Multivariate analyses revealed that younger age (HR=0.71, P=0.003), without extracranial metastases (HR=0.65, P<0.001) and radiation for BM (HR=0.78, P=0.005) were independent factors for better OS. Conclusion Improved survival of patients received BM resection was observed in SYSUCC cohort as comparison with SEER patients with NSCLC and BM. Aggressive local treatment including surgery and radiation is still important in Modern management of BM from NSCLC.

Skeletal Metastases in a Treated Case of WHO Grade IV Glioma without Relapse of Primary Tumor: A Rare Entity

Glioblastoma is the most common primary malignant brain tumors of the adult with a very dismal prognosis, representing 12-15% of all intracranial tumors in adult. The mean age of survival after diagnosis is approximately 14.6 months despite treatment. However, extracranial metastases are rare in the case of glioblastoma. We report a case of a 37-year-old female who had right frontal lobe glioblastoma and was operated on in December 2019 and received radiotherapy. There was complete remission of the tumor. After 1 year, she developed a low backache and pain in her right hip. Investigations revealed new-onset lesions in the bones. HPE proved the lesions to be metastatic glioblastoma.

Clinical and pathological characteristics of breast cancer with resected brain metastasis.

1089 Background: Breast cancer brain metastasis (BCBM) has poor prognosis and limited therapeutic options. Studies have shown that BCBM may differ from their matched primary tumors in receptor subtypes and genomic characteristics. However, studies have been limited by the tissue availability of BCBM. Taking advantage of our institutional database of resected BCBM with matched primary breast samples, this study aimed to investigate the clinical and pathological characteristics of patients with resected BCBM. Methods: We performed retrospective chart review for all breast cancer patients who had resected BCBM samples at our institution over the last 20 years. Hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status of the primary breast and BCBM samples, location of BCBM, and extracranial metastases at time of BCBM diagnosis were categorized. Overall survival (OS) from time of BCBM diagnosis was calculated using the Kaplan-Meier method. Progression interval and receptor subtype switching from primary diagnosis to brain metastasis were computed and compared using Wilcoxon rank sum test and Fisher’s exact test, respectively. Results: Eighty-six patients were included in this study (median age at time of BCBM diagnosis 54.3 [range 28.3-84.0] years, median follow up 26.0 months). These included 47 HR+, 15 HER2+, 20 triple negative (TN), 4 unknown subtype breast samples, and 42 HR+, 18 HER2+, 17 TN and 9 unknown subtype brain samples. OS was significantly shorter in patients with TN compared to HR+ or HER2+ subtype, whether the TN status was in the primary breast tumor (median 20.5 vs 34.0 months, p = 0.04, thresholded at year 2) or in the brain metastasis (median 16.0 vs 34.0 months, p = 0.02, thresholded at year 2). No significant difference in OS was observed between HR+ and HER2+ groups. There was no significant difference in the progression interval from primary diagnosis to brain metastasis among receptor subtypes. From primary tumor to brain metastasis, receptor subtype switching occurred in 10 out of 73 patients (13.7%) for estrogen, 20 out of 70 (28.6%) for progesterone (PR), and 6 out of 72 (8.3%) for HER2. Receptor subtype switching did not significantly correlate with OS. Presence of extracranial metastases at time of BCBM diagnosis corresponded to significantly lower OS compared to no extracranial metastasis (16.5 vs 36.0 months, p = 0.01). No significant difference in OS was observed between patients with cerebral vs cerebellar brain metastases. Conclusions: These data indicate that patients with TN BCBM disease have the worst overall survival among all receptor subtypes. Metastases in extracranial sites at time of BCBM diagnosis significantly decreased survival. Location of the brain metastasis and receptor subtype switching from primary diagnosis to BCBM, which was relatively infrequent outside of the PR group, did not significantly correlate with OS in this limited data set.

Clinical Oncology Research and Reports (E-ISSN: 2693-4787) Dear Dr. Wilma D. Heemsbergen, Greetings! I am writing this email to introduce our Journal “Clinical Oncology Research and Reports” due for release our upcoming issue in the End of May. We have just gone through your published manuscript which was quite interesting “Breast-shape changes during radiation therapy after breast-conserving surgery” so we would like to publish your valuable manuscript in our Journal too. We believe that your research experience and abundance of knowledge will help us in spreading the scientific knowledge throughout the world, we request you to kindly submit your unpublished manuscript towards our esteemed Journal. Note: If you are interested in joining our Editorial/Reviewer Board please send your CV and a recent photograph We look forward to a long-lasting scientific relationship. Best Regards, Tracy Roy Editorial Coordinator Clinical Oncology Research and Reports Disclaimer: If you don’t want to wish to get emails from us please revert us with unsubscribe

Extracranial metastases from glioblastoma multiforme (GBM) are rare, especially cutaneous metastasis. However, the metastatic mechanism of GBM remains unknown with no current consensus regarding the best therapeutic regimen. We report the clinical, imaging and pathological features of a case of a 47 years old man with primary glioblastoma; who 12 months after receiving a macroscopically total resection and adjacent radiotherapy, developed scalp metastasis and subsequent multiple skin metastasis. We also discuss the details of this case in comparison with the previously reported cases in literature in terms of clinical presentation, lesions’ site, management and survival.

A late systemic and brain metastasis from subcutaneous leiomyosarcoma of the right forearm: a case report and review of the literature

Background Leiomyosarcomas are rare malignant tumors which originate from smooth muscle cells and very seldom give rise to intracerebral metastases. Nearly all cases of intracranial metastases stem from leiomyosarcomas of the uterus. We present a 61-year-old Caucasian man who developed multiple intracranial and extracranial metastases from leiomyosarcoma of the right forearm, diagnosed and treated 9 years before the current presentation. Case presentation The Caucasian patient presented to the emergency department due to a progressive hemiparesis on the left side. Magnetic resonance imaging scans of the neurocranium showed multiple intracerebral masses with perifocal edema. One of these was located in the right parietal lobe, corresponding to the hemiparesis. The patient underwent microsurgical complete resection of the parietal mass and was subsequently subjected to further radiotherapy. Histopathological studies revealed metastasis of the former leiomyosarcoma. Conclusions Leiomyosarcomas represent a rare entity of mesenchymal tumors. Intracerebral metastasis of these tumors is even less frequent. This case shows the importance of long-term follow-up in patients with leiomyosarcoma.