Breast cancer brain metastasis: Current evidence and future directions

Sun, Hongna; Xu, Junnan; Dai, Shuang; Ma, Yiwen; Sun, Tao

doi:10.1002/cam4.5021

Cited by 32 publications

(31 citation statements)

References 121 publications

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“…MBC is more likely to metastasize to liver (15%–32.0%), lung (21%–32.0%), bone (30%–60.0%) and brain (4%–10.0%) 15,16 . The proportion of brain metastasis is relatively low, which may be related to a special brain structure (blood–brain barrier) 17 . A total of 55 patients were included in this study, 15 patients with liver metastasis (27.3%), 33 patients with lung metastasis (60.0%), six patients with brain metastasis (10.9%) and 21 patients with bone metastasis (38.2%), which is consistent with previous studies 18– 21 .…”

Section: Discussionmentioning

confidence: 99%

Efficacy of anlotinib in Chinese patients with metastatic breast cancer: A retrospective observational study

Liu,

Zhi,

Zhang

2023

J Cellular Molecular Medi

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Anlotinib, a multitarget tyrosine kinase inhibitor, can inhibit tumour angiogenesis proliferation, metastasis, promote vascular normalization, increase T cell and NK cell activity and infiltration, remodel tumour microenvironment and synergistic immune enhancement. Our study aimes to evaluate the efficacy of anlotinib in the treatment of advanced metastatic breast cancer (MBC) after multiple lines of therapy. Patients included were treated with anlotinib for advanced MBC in the Affiliated Cancer Hospital of Zhengzhou University from 1 January 2019 to 30 June 2023. The objective remission rate, disease‐free progression survival and adverse reactions were analysed. We compared and analysed the efficacy of anlotinib in the treatment of advanced metastatic breast cancer, which showed that ORR was 23.6% and DCR was 69.1%. The DCR of monotherapy was 66.7% and that of combination therapy was 69.6% in MBC patients. The combination therapy, combined with chemotherapy had the best effect (79.3%), combined with immunotherapy came second. In addition, the DCR (88.9%) was higher in MBC patients having received prior antiangiogenic therapy. According to the Kaplan–Meier (K‐M) survival estimate analysis, the mPFS was 4.17 months (95% CI, 1.758–6.582 months) in Her‐2 positive MBC patients, and 7.83 months (95% CI, 2.416–9.104) in Her‐2 negative MBC patients. The mPFS was 5.76 months (95% CI, 3.231–8.298 m) in HR positive MBC patients, 7.83 months (95% CI, 3.182–12.478 m) in TNBC patients. Fatigue (20.0%), hypertension (21.8%) and liver dysfunction (18.2%) were common adverse reactions, followed by bone marrow suppression (16.4%), anorexia (14.5%), hypothyroidism (14.5%) and diarrhoea (14.5%). Altogether, Anlotinib monotherapy or combination therapy provides a viable third (or above)‐line therapeutic strategy in patients with metastatic breast cancer. The adverse reactions of anlotinib are well tolerated and controllable.

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Section: Discussionmentioning

confidence: 99%

Efficacy of anlotinib in Chinese patients with metastatic breast cancer: A retrospective observational study

Liu,

Zhi,

Zhang

2023

J Cellular Molecular Medi

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“…To spread to the brain, cancerous cells from the breast must adhere to endothelial cells that line the microvessel and subsequently penetrate the blood–brain barrier (BBB). − The BBB is a structure that isolates the blood in circulation from the brain tissue, establishing a stable environment crucial for proper neural function and activity. , It comprises endothelial cells forming the vessel walls, pericytes firmly embedded in basement membranes, and astrocytes enveloping the blood vessels . Dysfunction of the BBB may result in cognitive impairment and the onset of dementia and has been linked to neurodegenerative disorders. , The BBB has also been implicated in the permission of breast cancer cells’ extravasation and colonization of the brain. , Although a series of attempts were aimed at elucidating the molecular mechanism of breast cancer cell penetration of the BBB, there is a need for further investigation to unravel the metastatic process.…”

Section: Introductionmentioning

confidence: 99%

“…2 For this reason, coupled with low clinical research in this field, BCBM detection is too often delayed. 7 To spread to the brain, cancerous cells from the breast must adhere to endothelial cells that line the microvessel and subsequently penetrate the blood−brain barrier (BBB). 8−11 The BBB is a structure that isolates the blood in circulation from the brain tissue, establishing a stable environment crucial for proper neural function and activity.…”

Section: Introductionmentioning

confidence: 99%

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O-Glycome Profiling of Breast Cancer Cell Lines to Understand Breast Cancer Brain Metastasis

Onigbinde,

Peng,

Reddy

et al. 2024

J. Proteome Res.

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Breast cancer is the second leading cause of cancer-related death among women and a major source of brain metastases. Despite the increasing incidence of brain metastasis from breast cancer, the underlying mechanisms remain poorly understood. Altered glycosylation is known to play a role in various diseases including cancer metastasis. However, profiling studies of O-glycans and their isomers in breast cancer brain metastasis (BCBM) are scarce. This study analyzed the expression of O-glycans and their isomers in human breast cancer cell lines (MDA-MB-231, MDA-MB-361, HTB131, and HTB22), a brain cancer cell line (CRL-1620), and a brain metastatic breast cancer cell line (MDA-MB-231BR) using nanoLC-MS/MS, identifying 27 O-glycan compositions. We observed significant upregulation in the expression of HexNAc 1 Hex 1 NeuAc 2 and HexNAc 2 Hex 3 , whereas the expression of HexNAc 1 Hex 1 NeuAc 1 was downregulated in MDA-MB-231BR compared to other cell lines. In our isomeric analysis, we observed notable alterations in the isomeric forms of the O-glycan structure HexNAc 1 Hex 1 NeuAc 1 in a comparison of different cell lines. Our analysis of Oglycans and their isomers in cancer cells demonstrated that changes in their distribution can be related to the metastatic process. We believe that our investigation will contribute to an enhanced comprehension of the significance of O-glycans and their isomers in BCBM.

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“…Breast cancer brain metastasis (BCBM) is the second most common cause of brain metastasis, and its occurrence has been rising in the past two decades with signi cant improvement in the survival of advanced breast cancer patients [23]. The current treatment options for ER-positive breast cancer patients with brain metastases are limited, including surgical resection and local radiotherapy.…”

Section: Introductionmentioning

confidence: 99%

SCR-6852, an oral and highly brain-penetrating estrogen receptor degrader (SERD) effectively shrinks tumors both in intracranial and subcutaneous ER+ breast cancer models

Yang

Liu

et al. 2023

Preprint

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Background: Targeted estrogen receptor degradation has been approved to effectively treat ER + breast cancers. Due to the poor bioavailability of fulvestrant, the first generation of SERD, many efforts were made to develop oral SERDs. With the approval of Elacestrant, oral SERDs demonstrated superior efficacy than fulvestrant. However, due to the poor ability of known SERDs to penetrate the blood-brain barrier (BBB), breast cancer patients with brain metastasis cannot benefit from clinical SERDs.Methods The ER inhibitory effects were evaluated on ERα protein degradation, and target genes downregulation. And anti-proliferation activities were further determined in a panel of ER + breast cancer cell lines. The subcutaneous and intracranial ER + tumor models were used to evaluate the efficacy of anti-tumor effects. Brain penetrability was determined in multiple animal species.Results SCR-6852 is a novel SERD and currently is under early clinical evaluation. In vitro, studies demonstrated that it strongly induced both wildtype and mutant ERα degradation. It potently inhibited cell proliferation in a panel of ER + breast cancer cell lines, including the cell lines containing ESR1 mutations (Y537 and D538). Furthermore, SCR-6852 showed completely antagonistic activity on the ERɑ signal axis identified both in vitro and in vivo. Oral administration of SCR-6852 at 10mpk resulted in tumor shrinkage which was superior to Fulvestrant at 250mpk, Notably, in the intracranial tumor model, SCR-6852 effectively inhibited tumor growth and significantly prolonged mice survival, which correlated well with the high exposure in brains. In addition to mice, SCR-6852 also exhibited high brain penetrability in rats and dogs.Conclusions SCR-6852 is a best-in-class SERD with high potency in inducing ERα protein degradation and completely antagonistic activity on ERɑ signaling in vitro and in vivo. Due to the high brain penetrability, SCR-6852 could be used to treat breast patients with brain metastasis.

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Breast cancer brain metastasis: Current evidence and future directions

Cited by 32 publications

References 121 publications

Efficacy of anlotinib in Chinese patients with metastatic breast cancer: A retrospective observational study

Efficacy of anlotinib in Chinese patients with metastatic breast cancer: A retrospective observational study

O-Glycome Profiling of Breast Cancer Cell Lines to Understand Breast Cancer Brain Metastasis

SCR-6852, an oral and highly brain-penetrating estrogen receptor degrader (SERD) effectively shrinks tumors both in intracranial and subcutaneous ER+ breast cancer models

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