Breast cancer patients with brain metastasis undergoing GKRS

Abu-Khalaf, Maysa; Muralikrishnan, Sivraj; Canchi, Deepti; Yu, James B.; Chiang, Veronica

doi:10.1007/s12282-018-0903-3

Cited by 6 publications

(7 citation statements)

References 19 publications

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“…Firstly, regarding the overall survival, an MST of 19.7 months was obtained, which is comparable with what is portrayed in different studies of radiosurgery treatment using GK-RS: Jo et al (MST 18.2 months) 32 , Matsunaga et al (MST 13 months) 33 or Abu-Khalaf (13.1 months) 34 , although the sample size of our study is smaller. Among the variables that we determined to be significant for the overall survival of the patients in our study are the KPS, the molecular subtype and the modified breast-GPA.…”

Section: Discussionsupporting

confidence: 89%

“…En primer lugar, en lo que respecta a la supervivencia global, se obtuvo un MST de 19.7 meses, que es comparable con lo que se muestra en diferentes estudios de tratamiento de radiocirugía con GK-RS: Jo et al (MST 18.2 meses) 32 , Matsunaga et al (MST 13 meses) 33 o Abu-Khalaf (13.1 meses) 34 , aunque el tamaño muestral de nuestro estudio es menor. Entre las variables que determinamos como significativas para la supervivencia global de las pacientes de nuestro estudio se encuentran el KPS, el subtipo molecular y el GPA modificado de cáncer de mama.…”

Section: Discussionunclassified

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Volumetric modulated arc radiosurgery for brain metastases from breast cancer: A single-center study

Sánchez-Villalobos¹,

Serna-Berna²,

Salinas-Ramos³

et al. 2021

Colomb Med

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Background: Whole-brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) are two treatment modalities commonly utilized to treat brain metastases (BMs). Aim: The purpose of this study is to analyze retrospectively the local control and survival of patients with BMs of breast cancer (BC) treated via radiosurgery using Volumetric Modulated Arc Therapy (VMAT-RS). Methods: 18 patients with 41 BMs of BC and treated by VMAT-RS were studied. They were classified according to the molecular subtype of BC and the modified breast graded prognostic assessment -GPA- index. Patients presented 1-4 BMs, which were treated with 5 non-coplanar VMAT arcs. The spatial distribution of BMs, the influence of receptor status on the location of the lesions and survival assessed via the Kaplan-Meier model were analyzed. Results: The median survival time (MST) was 19.7 months. Statistically significant differences were determined in the MST according to the Karnofsky performance status (p= 0.02) and the HER2 status (p= 0.004), being more prolonged in the HER2+ patients. Finally, our results showed that the cerebellum is the predominant site of breast cancer BMs, and also suggested that HER2+BMs had a predilection for some structures of the posterior circulation, such as the cerebellum, brainstem and occipital lobes (p= 0.048). Conclusions: The VMAT-RS is a technique with an overall survival compared to other radiosurgery techniques. The baseline situation at the time of treatment, the modified breast-GPA and the molecular subtypes are factors that significantly influence patient survival.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionunclassified

Volumetric modulated arc radiosurgery for brain metastases from breast cancer: A single-center study

Sánchez-Villalobos¹,

Serna-Berna²,

Salinas-Ramos³

et al. 2021

Colomb Med

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“…Brain metastases represent the most common intracranial neoplasm in adults, and breast cancer is the second most common cause of brain metastases 1 , 2 . Approximately 10% to 30% of breast cancer patients will develop brain metastases 3 .…”

Section: Introductionmentioning

confidence: 99%

Circular RNA circBCBM1 promotes breast cancer brain metastasis by modulating miR-125a/BRD4 axis

Fu¹,

Liu²,

Zhu³

et al. 2021

Int. J. Biol. Sci.

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Circular RNAs (circRNAs) play critical roles in tumorigenesis and the progression of various cancers. We previously identified a novel upregulated circRNA, circBCBM1 (hsa_circ_0001944), in the context of breast cancer brain metastasis. However, the potential biological function and molecular mechanism of circBCBM1 in breast cancer brain metastasis remain largely unknown. In this study, we confirmed that circBCBM1 was a stable and cytoplasmic circRNA. Functionally, circBCBM1 promoted the proliferation and migration of 231-BR cells in vitro and growth and brain metastasis in vivo . Mechanistically, circBCBM1 acted as an endogenous miR-125a sponge to inhibit miR-125a activity, resulting in the upregulation of BRD4 (bromodomain containing 4) and subsequent upregulation of MMP9 (matrix metallopeptidase 9) through Sonic hedgehog (SHH) signaling pathway. Importantly, circBCBM1 was markedly upregulated in the breast cancer brain metastasis cells and clinical tissue and plasma samples; besides, circBCBM1 overexpression in primary cancerous tissues was associated with shorter brain metastasis-free survival (BMFS) of breast cancer patients. These findings indicate that circBCBM1 is involved in breast cancer brain metastasis via circBCBM1/miR-125a/BRD4 axis. CircBCBM1 may serve as a novel diagnostic and prognostic biomarker and potential therapeutic target for breast cancer brain metastasis.

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“…3E). We further categorized the metastasis nodules into large (> 50 µm 2 ) and micro-metastases (≤ 50 µm 2 ) (Fig. 3F).…”

Section: Circbcbm1 Facilitates Growth and Brain Metastasis Of 231-br mentioning

confidence: 99%

“…Brain metastases represent the most common intracranial neoplasm in adults and breast cancer is the second most common cause of brain metastases [1,2]. Approximately 10-30% of breast cancer patients will develop brain metastases [3].…”

Section: Introductionmentioning

confidence: 99%

CircBCBM1 Promotes Breast Cancer Brain Metastasis via miR-125a/BRD4 Axis

Liu

et al. 2020

Preprint

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Background: Accumulating evidence indicates that circular RNAs (circRNAs) play critical roles in tumorigenesis and progression of various cancers. We previously identified a novel upregulated circRNA, circBCBM1 (hsa_circ_0001944), in the context of breast cancer brain metastasis. However, the potential biological function and molecular mechanism of circBCBM1 in breast cancer brain metastasis remain largely unknown.Methods: In this reserch, we validated the expression and characterization of circBCBM1 through RT-qPCR, Sanger sequencing, RNase R assay and fluorescence in situ hybridization (FISH). Functional experiments were performed to determine the effect of circBCBM1 on growth and metastasis of 231-BR cells both in vitro and in vivo. The regulatory mechanisms among circBCBM1, miR-125a (has-miR-125a-5p), and BRD4 (bromodomain containing 4) were investigated by RNA immunoprecipitation (RIP), RNA pull-down, luciferase reporter assay and western blot. Results: Our findings demonstrated that circBCBM1 is a stable and cytoplasmic circRNA. Functionally, silencing of circBCBM1 led to decreased proliferation and migration of 231-BR cells whereas elevated circBCBM1 expression showed reverse effects in vitro. These findings were confirmed in vivo in mouse models, as knockdown of circBCBM1 significantly decreased growth and brain metastases of 231-BR cells. Mechanistically, circBCBM1 functions as an endogenous miR-125a sponge to inhibit miR-125a activity, resulting in the upregulation of BRD4 expression and subsequent upregulation of MMP9 (matrix metallopeptidase 9) through Sonic hedgehog (SHH) signaling pathway. Importantly, circBCBM1 was markedly upregulated in the breast cancer brain metastasis cells and clinical tissue and plasma samples; besides, the overexpression of circBCBM1 in primary cancerous tissues was associated with shorter brain metastasis-free survival (BMFS) of breast cancer patients.Conclusions: These findings indicate that circBCBM1 is involved in breast cancer brain metastasis via circBCBM1/miR-125a/BRD4 axis, which sheds light on the pathogenic mechanism of circBCBM1 and provides translational evidence that circBCBM1 may serve as a novel diagnostic or prognostic biomarker and potential therapeutic target for breast cancer brain metastasis.

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Breast cancer patients with brain metastasis undergoing GKRS

Cited by 6 publications

References 19 publications

Volumetric modulated arc radiosurgery for brain metastases from breast cancer: A single-center study

Volumetric modulated arc radiosurgery for brain metastases from breast cancer: A single-center study

Circular RNA circBCBM1 promotes breast cancer brain metastasis by modulating miR-125a/BRD4 axis

CircBCBM1 Promotes Breast Cancer Brain Metastasis via miR-125a/BRD4 Axis

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