scholarly journals Liposomal Irinotecan Accumulates in Metastatic Lesions, Crosses the Blood-Tumor Barrier (BTB), and Prolongs Survival in an Experimental Model of Brain Metastases of Triple Negative Breast Cancer

2018 ◽  
Vol 35 (2) ◽  
Author(s):  
Afroz S. Mohammad ◽  
Jessica I. Griffith ◽  
Chris E. Adkins ◽  
Neal Shah ◽  
Emily Sechrest ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Experimental Model ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Metastatic Lesions ◽  
Liposomal Irinotecan

scholarly journals THER-06. GENOMIC AND IMMUNE CHARACTERIZATION OF TRIPLE NEGATIVE BREAST CANCER BRAIN METASTASES

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i11-i12
Author(s):  
Benjamin Vincent ◽  
Maria Sambade ◽  
Shengjie Chai ◽  
Marni Siegel ◽  
Luz Cuaboy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cell ◽  
Brain Metastases ◽  
T Cell Receptor ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cell Receptor ◽  
Gene Signature ◽  
Specific Response ◽  
Immune Gene

Abstract INTRODUCTION: Approximately 50% of patients with metastatic triple negative breast cancer (TNBC) will develop brain metastases (BM). Routinely treated with radiotherapy and/or surgery, survival is generally less than one year. There are no approved systemic therapies to treat TNBC BM. We characterized the genomic and immune landscape of TNBC BM to foster the development of effective brain permeable anti-cancer agents, including immunotherapy. EXPERIMENTAL PROCEDURES: A clinically-annotated BCBM biobank of archival tissues was created under IRB approval. DNA (tumor/normal) and RNA (tumor) were extracted from TNBC primaries and BM; whole exome (WES) and RNA sequencing (RNASeq) was performed. Mutations were determined from WES as those co-identified by two variant callers (Strelka|Cadabra). Immune gene signature expression, molecular subtype identification, and T cell receptor repertoires were inferred from RNAseq. RESULTS: 32 TNBC patient tissues (14 primaries, 18 BCBM, 6 primary-BCBM matched), characterized as basal-like by PAM50, were analyzed. Top exome mutation calls included ten genes in ≥19% of BCBMs including TP53, ATM, and PIK3R1, and four genes in ≥18% of primaries including TP53 and PIK3R1. Many immune gene signatures were lower in BM compared to primaries including B cell, dendritic cell, regulatory T cell, and IgG cluster (p< 0.05). A signature of PD-1 inhibition responsiveness was higher in BM compared with primaries (p< 0.05). BCBM T cell receptor repertoires showed higher evenness and lower read count (both p < 0.01) compared to primaries. CONCLUSIONS: TNBC BM compared to primaries that metastasize to the brain show lower immune gene signature expression, higher PD-1 inhibition response signature expression, and T cell receptor repertoire features less characteristic of an active antigen-specific response. Mutations common to TNBC BM and primaries include TP53 and PIK3R1. Given that non-BCBM (i.e. lung and melanoma) show response to checkpoint inhibitors, these findings collectively support further study of immunotherapy for TNBC BM.

The role of systemic treatment after whole brain radiotherapy (WBRT) in breast cancer patients with brain metastases: Differences depending on biological subtype

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1027-1027
Author(s):  
A. Niwinska ◽  
M. Murawska ◽  
I. Lemanska ◽  
J. Milewska
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Median Survival ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Systemic Treatment ◽  
Performance Status ◽  
Poor Performance Status ◽  
Breast Cancer Patients ◽  
Her 2

1027 Background: The aim of the study was to analyze the efficacy of systemic treatment (chemotherapy [chth], endocrine therapy, targeted therapy) performed after WBRT in patients (pts) with breast cancer and brain metastases. Methods: The group of 222 consecutive breast cancer pts with brain metastases treated in one institution in the years 2003–2006 was divided into four biological subgroups based on ER, PR, and HER-2 receptors’ expression: HER-2(+++)ER/PR(-); HER-2(+++)ER/PR(+); ER(-)PR(-)HER-2(-); and ER/PR(+)HER-2(-). WBRT was performed in 219 (99%) pts. Systemic therapy after WBRT was continued in 160 (72%) pts. Clinically, patients with triple-negative breast cancer were more often in poor performance status (KPS<60%) than the others (51% vs. 28%, respectively). Survivals from brain metastases without and with systemic treatment were compared in four mentioned biological subgroups. Results: Median survival from brain metastases in the entire group was 7.5 months. In the group of ER/PR(+)HER-2(-) median survival without and with systemic therapy was 3 and 14 months, respectively (p = 0.007). In the group of HER-2(+++)ER/PR(+) median survival without further treatment, after chth and after chth with trastuzumab was 2, 8, and 13 months, respectively (p = 0.000) and in the group of HER-2(+++)ER/PR(-) median survival without further treatment, after chth and after chth with trastuzumab was 4, 8, and 10 months, respectively (p = 0.004). In triple-negative breast cancer patients median survival without and with chemotherapy was 3 and 4 months, respectively (p = 0.75). Conclusions: Systemic treatment (chth, endocrine therapy, targeted therapy) continued after WBRT in breast cancer pts with brain metastases prolongs survival in three of four biological subgroups. In the group of HER-2-positive breast cancer pts, trastuzumab added to chth had independent positive impact on survival. No benefit was observed in the subgroup of triple-negative breast cancer pts; it would be the result of refractory disease and the fact, that more pts were in poor performance status. No significant financial relationships to disclose.

TBCRC 018: Phase II study of iniparib plus chemotherapy to treat triple-negative breast cancer (TNBC) brain metastases (BM).

2011 ◽  
Vol 29 (15_suppl) ◽  
pp. TPS127-TPS127 ◽  
Author(s):  
C. K. Anders ◽  
R. Nanda ◽  
M. C. Liu ◽  
K. L. Blackwell ◽  
C. H. Van Poznak ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Phase Ii ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Phase Ii Study

scholarly journals Apatinib + CPT-11 + S-1 for treatment of refractory brain metastases in patient with triple-negative breast cancer

Medicine ◽  
2018 ◽  
Vol 97 (15) ◽  
pp. e0349 ◽  
Author(s):  
Ting Hu ◽  
Cuiwei Liu ◽  
Qiuhui Li ◽  
Jie Xiong ◽  
Yuxi Ma ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Triple Negative Breast Cancer ◽  
Triple Negative

scholarly journals RADI-17. Outcomes for patients with triple negative breast cancer treated with upfront stereotactic radiosurgery for brain metastases

2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii21-iii21
Author(s):  
Ran An ◽  
Yan Wang ◽  
Fuchenchu Wang ◽  
Akshara Singareeka Raghavendra ◽  
Chao Gao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factors ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Univariate Analysis ◽  
Karnofsky Performance Score ◽  
Risk Of Death ◽  
Metastatic Sites

Abstract Background Triple-negative breast cancer (TNBC) is an aggressive subtype with high propensity of developing brain metastases (BM). Clinical outcomes and prognostic factors after stereotactic radiosurgery (SRS) for BM were not well defined. Methods We identified 57 consecutive TNBC patients (pts) treated with single fraction SRS for BM during 05/2008–04/2018. Overall survival (OS) from BM diagnosis and freedom from BM progression (FFBMP) after initial SRS were evaluated. BM progression was defined as local and/or distant brain failure (LBF, DBF) after SRS. Kaplan-Meier analyses and Cox proportional hazard regression were used to estimate survival outcomes and identify prognostic factors. Results The median time to BM development from TNBC diagnosis was 23.7 months (mo) (range 0.7‒271.1). Median OS was 13.1 mo (95%CI 8.0‒19.5). On univariate analysis, Karnofsky performance score (KPS) &gt;70 (p=0.03), number of BMs &lt;3 (p=0.016), and BM among the first metastatic sites (p=0.04) were associated with longer OS. On multivariate analysis, KPS ≤70 was associated with higher risk of death (HR 3.0, p=0.03). Of 46 pts with adequate imaging follow-up, 29 (63%) had intracranial progression with a median FFBMP of 7.4 mo (95% CI 5.7–12.7). At 12 mo the estimated cumulative DBF rate was 61.1% (95%CI 40.8%–74.4%) and LBF rate was 17.8% (95%CI 2%–31.1%). Number of BMs (≥3 vs &lt;3) was not associated with FFBMP (p=0.7). Of the 29 pts with BM progression, additional radiation therapy (RT) (vs. no RT) was associated with improved survival (21.7 vs. 7.0 mo, p&lt;0.0001). Conclusions TNBC pts with BM treated with SRS had an OS of 13.1 mo and FFBMP of 7.4 mo. Good KPS was an independent prognostic factor for OS. Further studies with more pts or conducted prospectively are needed to better understand and to improve treatment outcomes in this pt population.

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