scholarly journals 33. SYSTEMATIC REVIEW AND META-ANALYSIS OF BREAST CANCER BRAIN METASTASIS AND PRIMARY TUMOR RECEPTOR EXPRESSION DISCORDANCE

2020 ◽  
Vol 2 (Supplement_2) ◽  
pp. ii6-ii6
Author(s):  
Rupesh Kotecha ◽  
Raees Tonse ◽  
Muni Rubens ◽  
Michael McDermott ◽  
Yazmin Odia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Brain Metastasis ◽  
Primary Tumor ◽  
Expression Profiles ◽  
Receptor Expression ◽  
Her2 Status ◽  
Tumor Subtype ◽  
Primary Tumors ◽  
Breast Cancer Brain Metastasis

Abstract BACKGROUND Discordance in hormone receptor (estrogen [ER] and progesterone [PR]) and human epidermal growth factor receptor2 (HER2) status between the primary tumor and brain metastases and its effect on tumor classification subtype switching has been described but remains understudied. METHODS Using the PRISMA guidelines, a systematic review was performed of series published prior to April 2020 of biopsied or resected breast cancer brain metastasis (BCBM) from the Medline database using the keywords “breast cancer” and “brain metastasis” combined with “estrogen receptor/ER,” “progesterone receptor/PR,” “HER2/neu,” and “receptor conversion/dis- or concordance.” Weighted random effects models were used to calculate pooled estimates. RESULTS Fifteen full-text articles met inclusion criteria and cumulatively reported on 1373 patients who underwent biopsy or resection of at least one BCBM to compare to their primary tumor. At initial diagnosis, receptor expression profiles were 45.0% ER+, 41.0% ER-, 31.0% PR+, 51.0% PR-, 35% HER2+, and 47.0% HER2-. Corresponding receptor expression profiles from the BCBM were 19.0% ER+, 31.0% ER-, 13.0% PR+, 40.0% PR-, 21.0% HER2+, and 26.0% HER2-. Intra-patient receptor discordance comparisons revealed that 540 patients (42.6%) exhibited discordance in any receptor with 17.0% (95% CI: 13.0%-23.0%) discordance for ER status, 23.0% (95% CI: 18.0%-30.0%) for PR status, and 12.0% (95% CI: 8.0%-16.0%) for HER2 status. The most common receptor discordance events found in BCBM compared to primary tumors were ER loss 11.0% (95% CI: 8.0%-16.0%), PR loss 15.0% (95% CI: 11.0%-21.0%), and HER2 gain 9.0% (95% CI: 7.0%-11.0%). CONCLUSIONS BCBM commonly exhibit receptor expression changes on comparison to primary tumors including a 10% HER2 gain rate, a potential actionable target. Classification patterns need to be updated to reflect changes in overall tumor subtype grouping and which factors predict for BCBM/primary tumor discordance. Overall, tumor subtype switching and its effect on clinical management remains underappreciated.

scholarly journals Systematic Review and Meta-analysis of Breast Cancer Brain Metastasis and Primary Tumor Receptor Expression Discordance

2021 ◽  
Author(s):  
Rupesh Kotecha ◽  
Raees Tonse ◽  
Muni Rubens ◽  
Michael W McDermott ◽  
Yazmin Odia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Brain Metastasis ◽  
Primary Tumor ◽  
Meta Analysis ◽  
Metastatic Breast ◽  
Receptor Expression ◽  
Her2 Status ◽  
Primary Tumors ◽  
Breast Cancer Brain Metastasis

Abstract Background Change in hormone receptor (estrogen [ER] and progesterone [PR]) and/or HER2 status during the evolutionary course of metastatic breast cancer and the effect of tumor classification subtype switching remain understudied and underappreciated in brain metastasis patients. Methods Using PRISMA guidelines, a systematic review of series published prior to April 2020 obtained from the Medline database of biopsied or resected breast cancer brain metastasis (BCBM) was performed. Weighted random effects models were used to calculate pooled estimates. Results 15 full-text articles were included with receptor expression analyses on 1373 patients who underwent biopsy or resection of at least one intracranial lesion to compare to the primary tumor. Primary tumor receptor expression immunophenotypes were 45.0% ER+, 41.0% ER-, 31.0% PR+, 51.0% PR-, 35% HER2+, and 47.0% HER2-. Corresponding BCBM immunophenotypes were 19.0% ER+, 31.0% ER-, 13.0% PR+, 40.0% PR-, 21.0% HER2+, and 26.0% HER2-. On primary/BCBM comparison, 540 patients (42.6%) exhibited discordance in any receptor with 17.0% (95% CI: 13.0%-23.0%) discordant on ER, 23.0% (95% CI: 18.0%-30.0%) discordant on PR, and 12.0% (95% CI: 8.0%-16.0%) discordant on HER2 status. The most common receptor conversions found in BCBM were ER loss 11.0% (95% CI: 8.0%-16.0%), PR loss 15.0% (95% CI: 11.0%-21.0%), and HER2 gain 9.0% (95% CI: 7.0%-11.0%). Conclusions BCBM exhibit significant receptor expression discordance in comparison to primary tumors in approximately 40% of patients. Classification patterns need to be analyzed to determine factors predictive of BCBM/primary tumor discordance. Overall, tumor subtype switching and its effect on clinical management remains underappreciated.

Number of tumor-infiltrating lymphocytes in breast cancer brain metastases compared to matched breast primaries.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 2049-2049 ◽  
Author(s):  
Jessie Narloch ◽  
Catherine Luedke ◽  
Gloria Broadwater ◽  
Nolan Priedigkeit ◽  
Allison Hall ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Tumor Infiltrating Lymphocytes ◽  
Cox Proportional Hazards Model ◽  
Her2 Status ◽  
Primary Tumors ◽  
Metastatic Setting ◽  
Breast Cancer Brain Metastasis ◽  
Infiltrating Lymphocytes

2049 Background: Breast cancer brain metastasis (BCBM) is frequent in advanced disease, has limited therapies, and is associated with poor prognosis. Increased stromal tumor infiltrating lymphocytes (sTILs) are prognostic in triple-negative breast cancer (TNBC) and predictive of therapeutic response in early breast cancer (BC). However, little is known about sTILs in the metastatic setting. We compared %sTILs between the largest known cohort of matched primary tumors and BCBM and correlated the results with clinical endpoints. Methods: We retrospectively investigated 37 matched primary tumors and BCBM tissue from three institutions. In addition, we identified 29 primary tumors from patients later diagnosed with BCBM. H&E-stained sections were manually measured for %sTILs using standard criteria. Wilcoxon signed rank tests assessed for changes in %sTILs between primary and metastatic lesions. A Cox proportional hazards model was used to determine if %sTILs in the breast tissue predicts time from primary tumor biopsy to diagnosis of brain metastasis (TTDBM) while adjusting for clinicopathologic features. Results: Average age at time of BCBM diagnosis was 53.6 (SD 12.3). 52% (34/66) of primary tumors were hormone receptor (HR) positive. Of 60 patients with known HER2 status, 28% (17) were HER2 positive and 40% (24) TNBC. Median %sTILS was significantly different between all primary tumors (15, IQR 5-20) and brain metastases (10, IQR 5-10), p = 0.001. The TNBC subtype (n = 11) showed the largest decrease in %sTILs between primary tumors (20, IQR 10-20) and brain metastases (5, IQR 5-10), p = 0.022. Comparing primary tumors and brain metastases, there was a 5% decrease in %sTILs in HR-/HER2+ (n = 5, p = 0.13) and HR+/HER2- (n = 7, p = 0.13), and a 5% increase in %sTILs in the HR+/Her2+ subtype (n = 9, p = 0.69). Percent sTILs in the primary tumors was not a significant predictor of TTDBM, when adjusting for race, age, HR status, and HER2 status, p = 0.87. Conclusions: BCBM have a significantly decreased %sTILs compared to their primary tumors, most prominent in TNBC. These results suggest altered tumor immunogenicity in the metastatic setting which has broad implications for the development of immunotherapy.

scholarly journals OTHR-07. Systematic Review and Meta-analysis of Lung Cancer Brain Metastasis and Primary Tumor PD-L1 Expression Discordance

2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii15-iii16
Author(s):  
Raees Tonse ◽  
Muni Rubens ◽  
Haley Appel ◽  
Martin C Tom ◽  
Matthew D Hall ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Systematic Review ◽  
Brain Metastasis ◽  
Tumor Cell ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Primary Tumor ◽  
Small Cell ◽  
Receptor Expression ◽  
Small Cell Lung

Abstract Background Novel immunotherapeutic strategies, such as those targeting the PD-1/PD-L1 axis, are promising in patients with metastatic lung cancer and are often administered when tumors show PD-L1 positivity. The objective of this study was to analyze PD-L1 receptor discordance in tumor cell between the primary tumor and lung cancer brain metastasis (LCBM). Methods A systematic review of series published prior to April 2021 obtained from the Medline database of biopsied or resected LCBM evaluating PD-L1 discordance was performed using PRISMA guidelines. Weighted random effects models were used to calculate pooled estimates. Results Six full-text articles (n=247 patients) with a median of 32 patients in each study (range: 24–73 patients) reported PD-L1 receptor expression analyses of both primary lung tumors and brain metastases. The majority of patients (81%) were smokers, with 67% non-small cell lung cancer and 33% small cell lung cancer. The pooled estimate for overall PD-LI receptor concordance between primary and LCBM was 76% (95% CI: 52%-90). The positivity rate varied when analyzed by various cutoff levels of PD-L1 expression; for <1% expression, it was 41% (95% CI: 22%-62%) for primary vs. 58% (95% CI: 35%-78%) for LCBM; for PD-L1 expression of 1–50%, it was 24% (95% CI: 13%-40%) vs. 19% (95% CI: 10%-33%); and for PD-L1 >50% it was 12% (95% CI: 4%-33%) vs. 21% (95% CI: 14%-29%) (p=0.425). The pooled estimate for overall PD-LI receptor discordance between primary and LCBM was 17% (95% CI: 10%-27%). Meta-regression analysis showed that age, sex, smoking status, and histology were not associated with PD-LI receptor discordance. Conclusions PD-L1 status discordance in tumor cell occurs in approximately 20% of LCBM, with the greatest discordance in the <1% expression category. Awareness of this discordance is important for the selection of immune checkpoint inhibitor therapy as well as in the analysis of patterns of failures.

scholarly journals Systematic Review and Meta-analysis of PD-L1 Expression Discordance between Primary Tumor and Lung Cancer Brain Metastasis

2021 ◽  
Author(s):  
Raees Tonse ◽  
Muni Rubens ◽  
Haley Appel ◽  
Martin C Tom ◽  
Matthew D Hall ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Systematic Review ◽  
Brain Metastasis ◽  
Meta Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Receptor Expression ◽  
Primary Tumors ◽  
Random Effects Models ◽  
Expression Category ◽  
Metastatic Sites

Abstract Background Novel immunotherapeutic strategies targeting the PD-1/PD-L1 axis are often administered when metastatic tumors show PD-L1 positivity, even in the setting of lung cancer brain metastasis (LCBM). However, biological differences exist between primary tumors and metastatic sites. The objective of this study was to analyze rates of PD-L1 receptor discordance between primary tumors and LCBM. Methods A systematic review of studies of biopsied or resected LCBM evaluating PD-L1 discordance published in the Medline database was performed using PRISMA guidelines. Weighted random effects models were used to calculate pooled estimates. Results Six full-text articles (n=230 patients) with a median of 32 patients in each study (range: 24-73) reported PD-L1 receptor expression analyses of both primary lung tumors and brain metastases and met inclusion criteria. The pooled estimate for tumor cell (TC) PD-L1 receptor discordance between primary tumors and LCBM was 19% (95% CI: 10%-27%). For PD-L1 receptor expression in tumor infiltrating lymphocytes (TIL), the weighted pooled estimate for discordance was 21% (95% CI: 8%-44%). For primary versus LCBM, the positive rates by expression levels of <1%, 1-50%, and >50% were 52% (95% CI: 30-73%) vs. 56% (95% CI: 34-76%), 30% (95% CI: 22-40%) vs. 20% (95% CI: 10-35%), and 15% (95% CI: 6-36%) vs. 22% (95% CI: 15-31%) (p=0.425), respectively. Conclusions PD-L1 discordance occurs in ~20% of LCBM, with the greatest discordance in the 1-50% expression category. Although controversial, confirming discordance might be important for selection of immune checkpoint inhibitor therapy and in the analysis of patterns of failure after treatment.

scholarly journals Estrogen/progesterone receptor and HER2 discordance between primary tumor and brain metastases in breast cancer and its effect on treatment and survival

2020 ◽  
Vol 22 (9) ◽  
pp. 1359-1367 ◽  
Author(s):  
Paul W Sperduto ◽  
Shane Mesko ◽  
Jing Li ◽  
Daniel Cagney ◽  
Ayal Aizer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Primary Tumor ◽  
Hormone Receptors ◽  
Statistical Significance ◽  
Growth Factor Receptor ◽  
Subsequent Treatment ◽  
Her2 Status ◽  
Primary Tumors ◽  
Discordance Rate

Abstract Background Breast cancer treatment is based on estrogen receptors (ERs), progesterone receptors (PRs), and human epidermal growth factor receptor 2 (HER2). At the time of metastasis, receptor status can be discordant from that at initial diagnosis. The purpose of this study was to determine the incidence of discordance and its effect on survival and subsequent treatment in patients with breast cancer brain metastases (BCBM). Methods A retrospective database of 316 patients who underwent craniotomy for BCBM between 2006 and 2017 was created. Discordance was considered present if the ER, PR, or HER2 status differed between the primary tumor and the BCBM. Results The overall receptor discordance rate was 132/316 (42%), and the subtype discordance rate was 100/316 (32%). Hormone receptors (HR, either ER or PR) were gained in 40/160 (25%) patients with HR-negative primary tumors. HER2 was gained in 22/173 (13%) patients with HER2-negative primary tumors. Subsequent treatment was not adjusted for most patients who gained receptors—nonetheless, median survival (MS) improved but did not reach statistical significance (HR, 17–28 mo, P = 0.12; HER2, 15–19 mo, P = 0.39). MS for patients who lost receptors was worse (HR, 27–18 mo, P = 0.02; HER2, 30–18 mo, P = 0.08). Conclusions Receptor discordance between primary tumor and BCBM is common, adversely affects survival if receptors are lost, and represents a missed opportunity for use of effective treatments if receptors are gained. Receptor analysis of BCBM is indicated when clinically appropriate. Treatment should be adjusted accordingly. Key Points 1. Receptor discordance alters subtype in 32% of BCBM patients. 2. The frequency of receptor gain for HR and HER2 was 25% and 13%, respectively. 3. If receptors are lost, survival suffers. If receptors are gained, consider targeted treatment.

scholarly journals BSCI-13. TUMOR-SPECIFIC tGLI1 TRANSCRIPTION FACTOR MEDIATES BREAST CANCER BRAIN METASTASIS VIA ACTIVATING METASTASIS-INITIATING CANCER STEM CELLS AND ASTROCYTES IN THE TUMOR MICROENVIRONMENT

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i3-i3
Author(s):  
Sherona Sirkisoon ◽  
Richard Carpenter ◽  
Tadas Rimkus ◽  
Daniel Doheny ◽  
Dongqin Zhu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Brain Metastasis ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Ectopic Expression ◽  
Tumor Type ◽  
Primary Tumors ◽  
Breast Cancer Brain Metastasis

Abstract Breast cancer is the second leading cause of brain metastases in women; patients with breast cancer brain metastasis (BCBM) survive only 6–18 months after diagnosis. Mechanisms for BCBM remain unclear, which contributes to ineffective treatments and dismal prognosis. Truncated glioma-associated oncogene homolog 1 (tGLI1) belongs to the GLI1 family of zinc-finger transcription factors and functions as a tumor-specific gain-of-function mediator of tumor invasion and angiogenesis. Whether tGLI1 plays any role in metastasis of any tumor type remains unknown. Using an experimental metastasis mouse model, via intracardiac implantation, we showed that ectopic expression of tGLI1, but not GLI1, promoted preferential metastasis to brain. Conversely, selective tGLI1 knockdown using tGLI1-specific antisense oligonucleotides led to decreased brain metastasis of intracardially inoculated breast cancer cells. Furthermore, intracranial implantation mouse study revealed tGLI1 enhanced intracranial colonization and growth of breast cancer cells. Immunohistochemical staining of patient samples showed that tGLI1, but not GLI1, was increased in lymph node metastases compared to matched primary tumors, and that tGLI1 was expressed at higher levels in BCBM specimens compared to primary tumors. Whether tGLI1 plays any role in radioresistance is unknown; we found radioresistant BCBM cell lines and patient specimens expressed higher levels of tGLI1 than radiosensitive counterparts, and that tGLI1 promotes radioresistance. Since cancer stem cells (CSCs) are highly metastatic and radioresistant, we examined whether tGLI1 promotes BCBM and radioresistance through activating CSCs. Results showed that tGLI1 transcriptionally activates stemness genes CD44, Nanog, Sox2, and OCT4, leading to stem cell activation. Furthermore, we observed that tGLI1-positive CSCs strongly activated and interacted with astrocytes, the most abundant brain tumor microenvironmental cells known to promote tumor growth, in vitro and in vivo. Collectively, our findings establish a novel role of that tGLI1 plays in promoting breast cancer preferential metastasis to brain, radioresistance, and astrocytes in the metastatic niche.

P14.03 Shifting trends and entity-specific aspects in patients with brain metastasis: real-life analysis from 6031 individuals over an observation period of 30 years

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii38-ii38
Author(s):  
A Steindl ◽  
T J Brunner ◽  
K Heimbach ◽  
K Schweighart ◽  
G M Moser ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lung Cancer ◽  
Brain Metastasis ◽  
Primary Tumor ◽  
Renal Cell ◽  
Cell Cancer ◽  
Real Life ◽  
Neurosurgical Procedures ◽  
Primary Tumors ◽  
Observation Period

Abstract BACKGROUND We aimed to investigate the changing clinical characteristics of patients with brain metastases (BM) over the last three decades as the foundation for modern BM specific clinical trial planning. MATERIAL AND METHODS 6031 patients with newly diagnosed BM from different solid tumors treated between 1986–2020 were identified from the Vienna Brain Metastasis Registry. RESULTS The fraction of BM originating from the most common BM causing primary tumors (lung cancer, breast cancer and melanoma) was stable over the observation period from 1986–2020. BM from renal cell carcinoma, colorectal cancer and cancer of unknown primary (CUP) decreased over time (p<0.001). Synchronous diagnosis of BM and primary tumor was more frequently observed in lung cancer and CUP patients compared to breast cancer patients (p<0.001). An increasing fraction of patients presented with asymptomatic BM (1986–1999: 20.2% vs. 2010–2020: 30.4%; p<0.001), specifically in lung cancer (p<0.001), melanoma (p<0.001) and renal cell cancer (p=0.004). A decrease of neurosurgical procedures (1986–1999: 39.3% vs. 2010–2020: 20.4%) and an increase of radiation treatments (1986–1999: 56.5% vs. 2010–2020: 73.0%) and systemic therapies (1986–1999: 0.6% vs. 2010–2020: 2.4%; p<0.001) was observed. Furthermore, median overall survival significantly increased across entities (1986–1999: 5 months vs. 2010–2020: 7 months; p=0.001). Intracranial progression as the cause of death increased across entities (p< 0.001). The prognostic DS-GPA (Hazard ratio [HR] 1.42; p< 0.001) and the Lung-molGPA (HR 1.67; p<0.001) could be validated. CONCLUSION We observed changes of BM presentation and clinical parameters during the observation period depending on primary tumor origins. Future BM studies should follow an entity-specific approach and address the characteristics of modern BM cohorts.

scholarly journals 67. INCREASED RISK OF BREAST CANCER BRAIN METASTASIS WITH EGFR AND Ki-67 EXPRESSION: A SYSTEMATIC REVIEW AND META-ANALYSIS

2020 ◽  
Vol 2 (Supplement_2) ◽  
pp. ii14-ii14
Author(s):  
Arun Job ◽  
Alexander Hulsbergen ◽  
Ray Jhun ◽  
Charissa Jessurun ◽  
Timothy Smith ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Brain Metastasis ◽  
Prediction Models ◽  
Significant Risk ◽  
Pooled Analysis ◽  
Ki 67 ◽  
P53 Expression ◽  
Increased Risk ◽  
Breast Cancer Brain Metastasis

Abstract PURPOSE This study aims to conduct a systematic review of the literature to identify biomarkers associated with breast cancer brain metastasis (BCBM). METHODS A systematic search was conducted in PubMed, Embase, Web of Science, and Cochrane for relevant literature up until October 1, 2018. Case reports, conference abstracts, and expert opinions/letters were excluded. Studies were included if they investigated risk factors for BCBM in a cohort of patients with locoregional or metastatic breast cancer of any subtype. RESULTS From the 4866 studies that were screened, 117 were selected for inclusion and review. Twenty-eight unique biomarkers were investigated, of which three (EGFR, Ki-67, and p53) were assessed by more than two authors. In a pooled analysis of 3 studies, EGFR expression was associated with an increased risk of BM (RR 3.48, 95% CI 2.27–5.32, I2=0%, p-interaction = 0.39, n= 571 patients). In a pooled analysis of 5 studies, increased Ki-67 expression was associated with an increased risk of BM (RR 2.91, 95% CI 1.96–4.32, I2=59%, p-interaction = 0.05, n= 1,178). In a pooled analysis of 4 studies, p53 expression was not associated with a statistically significant risk of BM (RR 1.42, 95% CI 0.98–2.06, I2=53%, p-interaction = 0.10, n= 738). CONCLUSION This study summarizes the various biomarkers investigated for a role in breast cancer brain metastasis. Two biomarkers, EGFR and Ki-67 were identified as having a statistically significant increased risk of BCBM while p53 was not found to be statistically significant. Future studies are needed to develop more robust prediction models, as well as evaluate the other biomarkers identified in this study, which could help clinicians identify patients at high risk of breast cancer brain metastasis.

scholarly journals Subtype switching in breast cancer brain metastases: a multicenter analysis

2020 ◽  
Vol 22 (8) ◽  
pp. 1173-1181 ◽  
Author(s):  
Alexander F C Hulsbergen ◽  
An Claes ◽  
Vasileios K Kavouridis ◽  
Ali Ansaripour ◽  
Claudine Nogarede ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Growth Factor Receptor ◽  
Hazard Ratio ◽  
Receptor Expression ◽  
Her2 Status ◽  
Primary Tumors ◽  
Pathology Reports ◽  
Breast Cancer Brain Metastases ◽  
Extracranial Metastases

Abstract Background Breast cancer (BC) brain metastases (BM) can have discordant hormonal or human epidermal growth factor receptor 2 (HER2) expression compared with corresponding primary tumors. This study aimed to describe incidence, predictors, and survival outcomes of discordant receptors and associated subtype switching in BM. Methods BCBM patients seen at 4 tertiary institutions who had undergone BM resection or biopsy were included. Surgical pathology reports were retrospectively assessed to determine discordance between the primary tumor and the BCBM. In discordant cases, expression in extracranial metastases was also assessed. Results In BM from 219 patients, prevalence of any discordance was 36.3%; receptor-specific discordance was 16.7% for estrogen, 25.2% for progesterone, and 10.4% for HER2. Because estrogen and progesterone were considered together for hormonal status, 50 (22.8%) patients switched subtype as a result; 20 of these switches were HER2 based. Baseline subtype predicted switching, which occurred in up to 37.5% of primary HR+ patients. Moreover, 14.8% of initially HER2-negative patients gained HER2 in the BM. Most (63.6%) discordant patients with extracranial metastases also had discordance between BM and extracranial subtype. Loss of receptor expression was generally associated with worse survival, which appeared to be driven by estrogen loss (hazard ratio = 1.80, P = 0.03). Patients gaining HER2 status (n = 8) showed a nonsignificant tendency toward improved survival (hazard ratio = 0.64, P = 0.17). Conclusions In this multicenter study, we report incidence and predictors of subtype switching, the risk of which varies considerably by baseline subtype. Switches can have clinical implications for prognosis and treatment choice.

Comprehensive analysis of differentially expressed long noncoding RNAs, miRNAs and mRNAs in breast cancer brain metastasis

Epigenomics ◽  
2021 ◽  
Author(s):  
Meng An ◽  
Xiaowen Zang ◽  
Jimin Wang ◽  
Jie Kang ◽  
Xiaoyu Tan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Interaction Analysis ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Protein Protein Interaction ◽  
Real Time Quantitative Pcr ◽  
Breast Cancer Brain Metastasis

Aim: To delineate the transcriptomic landscape and potential molecular mechanisms of breast cancer brain metastasis (BCBM). Materials & methods: Whole-transcriptome sequencing was performed to identify long noncoding RNA (lncRNA), miRNA and mRNA expression profiles associated with BCBM. Results: A total of 739 differentially expressed lncRNAs, 115 differentially expressed miRNAs and 5749 differentially expressed mRNAs were identified in 231-BR cells compared with MDA-MB-231 cells. Real-time quantitative PCR results revealed the expression levels of candidate molecules were consistent with their correspondence RNA-seq data. Protein–protein interaction analysis identified some hub genes associated with BCBM, such as PTBP1, NUP98 and HYOU1. LncRNA-miRNA-mRNA network highlighted a potential mechanism of BCBM in which lncRNA FIRRE and RP11-169F17.1 sponging hsa-miR-501-5p to regulate the expression of MMS19, PTBP1 and NUP98. Conclusion: This study provides a framework for better understanding molecular mechanisms of BCBM.

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