Time to brain metastasis (TTBM) from initial diagnosis of distant metastasis in breast cancer: Prediction of TTBM according to breast cancer subtypes and treatment effect.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 644-644 ◽  
Author(s):  
Yeon Hee Park ◽  
Hee Kyung Ahn ◽  
Silvia Park ◽  
Chi Hoon Maeng ◽  
Su Jin Lee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Treatment Effect ◽  
Distant Metastasis ◽  
Therapeutic Strategy ◽  
Medical Center ◽  
Metastatic Breast ◽  
Initial Diagnosis ◽  
Cancer Subtypes ◽  
Cancer Prediction

644 Background: Brain metastasis (BM) from breast cancer (BC) is a growing problem. About 10-15% patients with metastatic breast cancer (MBC) developed BM, with a 1 year survival of 20%. Currently, one-third of MBC patients with either HER2+ve tumors or triple negative BC (TNBC) tumors develop brain metastases. We hypothesized that MBC patients may predispose to BM differently during the disease courses according to BC subtype and treatment. We analyzed TTBM from initial diagnosis of distant metastasis how BC subtypes and treatment affect on TTBM. Methods: We retrospectively investigated 189 consecutive patients who were diagnosed with BM from BC between 2000 and 2009 at Samsung Medical Center. We analyzed TTBM according to BC subtypes and treatment effect. Results: The median age of 189 BM patients from BC was 48 (range 26-87) years. The numbers of patients with hormone receptor (HR)+ve and HER2-ve, HER2+ve irrespective of HR status, and TNBC were 43 (22.8%), 88 (46.6%), and 58 (30.7%), respectively. Median TTBM of all 189 patients was 10.4 (95% CI, 7.7-13.1) months. We analyzed TTBC into four groups considering BC subtypes and treatment; HR+ve/HER2-ve (n=43), HER2+ve with trastuzumab (T) (n=59), HER2+ve without T (n=29), and TNBC patients (n=58). The median TTBMs for each group were 17.7 months, 13.8 months, 4.3 months, and 2.9 months, respectively (p=0.002). BM as an initial site of distant metastasis was much more common in HER2+ve without T and TNBC patients than in the other patients’ groups (40.2% vs 20.6%, p= 0.003). Conclusions: TTBMs were much shorter in patients with HER2+ve without T and TNBCs than in other BC patients. Different approaches for evaluation and therapeutic strategy for BM at the time of distant metastasis may be considered for these populations.

scholarly journals Breast cancer subtypes and the risk of distant metastasis at initial diagnosis: a population-based study

2018 ◽  
Vol Volume 10 ◽  
pp. 5329-5338 ◽  
Author(s):  
Weikai Xiao ◽  
Shaoquan Zheng ◽  
Anli Yang ◽  
Xingcai Zhang ◽  
Yutian Zou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Distant Metastasis ◽  
Population Based ◽  
Initial Diagnosis ◽  
Breast Cancer Subtypes ◽  
Population Based Study ◽  
Cancer Subtypes

α-basic-crystallin expression in basal-like breast cancer and its association with brain metastasis

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1025-1025
Author(s):  
H. F. Kennecke ◽  
D. Voduc ◽  
S. Leung ◽  
V. L. Cryns ◽  
C. M. Perou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Metastatic Disease ◽  
Distant Metastasis ◽  
Growth Factor Receptor ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Chi Square ◽  
Ki 67 ◽  
Cancer Subtypes

1025 Background: Basal-like breast cancers are high grade tumors with poor prognosis, having propensity for brain and lung metastasis (Perou et al. Nature 406:747–52, 2000, Cheang et al. Clin Cancer Res 14:1368–76, 2008, Luck et al. Clin Oncol (R Coll Radiol) 20:40–5, 2008). α-basic-crystallin (αBC), a small heat shock protein with anti-apoptotic and oncogenic activity, is expressed in about half of basal-like breast cancers but only 6% of other types (Moyano et al. J Clin Invest 116:261–70, 2006). Here we investigate the association of αBC with sites of distant metastasis in a large cohort of breast cancer patients. Methods: Our cohort consists of 4046 early invasive breast cancers referred to the British Columbia Cancer Agency from 1986 to 1992. Archival paraffin tissue blocks were used to construct tissue microarrays. Breast cancer subtypes were defined using a surrogate of six immunohistochemical markers: ER, PR, HER2, Ki-67, epidermal growth factor receptor and cytokeratin 5/6. αBC immunostaining was scored by pre-established, published criteria. All documented sites of distant metastasis were abstracted by chart review according to predefined categories. The null hypothesis was tested using chi-square and Fisher's Exact tests; all tests were two-sided. Results: Among 3,248 cases with interpretable αBC data, 11% were αBC +. Among patients who developed distant metastatic disease, the 10-yr BCSS survival in αBC+ and - tumors was 12% and 29%. Sites of metastatic disease included: brain (15%), lung (35%), liver (35%) and bone (65%). Brain metastasis was significantly more common among αBC positive tumors (Fisher's Exact test p<10e-8). Basal-like tumors with brain metastasis commonly co-expressed αBC (Chi-square p=0.006). Conclusion: αBC is significantly associated with brain metastasis, particularly among basal breast cancers. These findings suggested that αBC may be involved in tumor cell metastasis and may allow early identification of a subset of patients at particularly high risk of brain metastasis. [Table: see text] No significant financial relationships to disclose.

CA 15-3 elevations according to breast cancer subtypes at initial diagnosis of metastatic breast cancer (MBC).

2011 ◽  
Vol 29 (15_suppl) ◽  
pp. e11109-e11109
Author(s):  
S. Park ◽  
H. K. Ahn ◽  
T. Lim ◽  
Y. H. Park ◽  
J. S. Ahn ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Initial Diagnosis ◽  
Breast Cancer Subtypes ◽  
Cancer Subtypes

scholarly journals O28: M6A DEMETHYLASE FTO A POTENTIAL TARGET IN BRAIN METASTATIC BREAST CANCER

2021 ◽  
Vol 108 (Supplement_1) ◽  
Author(s):  
S Keelan ◽  
S Charmsaz ◽  
S Purcell ◽  
D Varešlija ◽  
S Cocchiglia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Brain Metastasis ◽  
Disease Progression ◽  
Therapeutic Target ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Potential Therapeutic Target ◽  
Rna Methylation ◽  
Pharmacological Inhibition

Abstract Introduction Brain metastasis (BrM) occurs in 10-30% of patients with advanced breast cancer (BC). BrM is increasing in incidence and confers a poor prognosis. We aimed to investigate the contribution of global epi-transcriptomic alterations in N6-methyladenosine (m6A) RNA-methylation as a therapeutic target in brain metastatic breast cancer. Method In preliminary studies we have demonstrated m6A demethylase – FTO as the main contributor to the progression of ER+ breast cancer. Furthermore an association between FTO and reduced disease-free-survival (n=870, p=0.018) was observed. Here we conducted an epigenetic inhibitor screen using two therapeutic agents, ethyl-ester-meclofenamic acid (MA2) and FB23-2 on matched 2D cell line, 3D organoid cultures and patient-derived xenografts (PDX) explant models of brain metastasis. Result Upon integration of mapped global RNA methylation landscape with matched proteomic analysis, we observed genome-wide RNA hypo-methylation of key pluripotency genes, including SOX2 and KLF4, as key players underlying tumour progression to the brain.  Genetic and pharmacological inhibition of FTO in novel ex vivo models of BrM significantly reduced protein expression levels of KLF4 and SOX2. Moreover, pharmacological inhibition of FTO with MA2 and FB23-2, inhibited cell proliferation in endocrine-resistant BC and patient BrM cells. We translate our findings to the clinic by demonstrating the efficacy of anti-FTO therapies in several unique PDX and 3D organoid BrM models. Conclusion Our results reveal epi-transcriptional remodelling events as a key mechanism in BrM. This study establishes an early role for targeting RNA methylation in the management of disease progression and presents FTO as a potential therapeutic target in BrM. Take-home message This study establishes an early role for targeting RNA methylation in the management of disease progression and presents FTO as a potential therapeutic target in brain metastatic breast cancer.

scholarly journals The gastrin releasing peptide, GRP, is differentially expressed in brain metastatic breast cancer.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Brain Metastasis ◽  
Microarray Data ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
Primary Tumors ◽  
Gastrin Releasing Peptide ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes to discover genes associated with brain metastasis in patients with metastatic breast cancer. We found that the gastrin releasing peptide, encoded by GRP, was among the genes whose expression was most different in the brain metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. Molecular functions of gastrin releasing peptide may be relevant to the processes by which tumor cells of the breast metastasize to the breast. Down-regulation of GRP may be an important event for metastasis of primary tumor-derived cancer cells to the brain in humans with metastatic breast cancer.

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