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 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 FGFR aberrations increase the risk of brain metastases and predict poor prognosis in metastatic breast cancer patients

2020 ◽  
Vol 12 ◽  
pp. 175883592091530
Author(s):  
Ning Xie ◽  
Can Tian ◽  
Hui Wu ◽  
Xiaohong Yang ◽  
Liping liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Brain Metastasis ◽  
Poor Prognosis ◽  
Significant Risk ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Genetic Aberrations ◽  
Increased Risk

Background: The survival status of patients with breast cancer and brain metastasis (BCBM) receiving current treatments is poor. Method: We designed a real-world study to investigate using patients’ clinical and genetic aberrations to forecast the prognoses of BCBM patients. We recruited 146 BCBM patients and analyzed their clinical features to evaluate the overall survival (OS). For genetic testing, 30 BCBM and 165 non-brain-metastatic (BM) metastatic breast cancer (MBC) patients from Hunan Cancer Hospital, and 86 BCBM and 1416 non-BM MBC patients from the Geneplus database who received circulating tumor DNA testing, were compared and analyzed. Results: Ki67 >14% and >3 metastatic brain tumors were significant risk factors associated with poor OS, while chemotherapy and brain radiotherapy were beneficial factors for better OS. Compared with non-BM MBC patients, BCBM patients had more fibroblast growth factor receptor ( FGFR) aberrations. The combination of FGFR, TP53 and FLT1 aberrations plus immunohistochemistry HER2-positive were associated with an increased risk of brain metastasis (AUC = 77.13%). FGFR aberration alone was not only a predictive factor (AUC = 67.90%), but also a significant risk factor for poor progression-free survival (Logrank p = 0.029). FGFR1 aberration was more frequent than other FGFR family genes in BCBM patients, and FGFR1 aberration was significantly higher in BCBM patients than non-BM MBC patients. Most FGFR1-amplified MBC patients progressed within 3 months of the late-line (>2 lines) treatment. Conclusion: A group of genetic events, including FGFR, TP53 and FLT1 genetic aberrations, and HER2-positivity, forecasted the occurrence of BM in breast cancers. FGFR genetic aberration alone predicted poor prognosis.

scholarly journals 29. ROLE OF AGE AND CNS MYELOID CELLS ON BREAST CANCER BRAIN METASTASIS

2020 ◽  
Vol 2 (Supplement_2) ◽  
pp. ii5-ii5
Author(s):  
Alex Man Lai Wu ◽  
Selamawit Gossa ◽  
Ramakrishna Samala ◽  
Monika Chung ◽  
Brunilde Gril ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Brain Metastasis ◽  
Cancer Metastasis ◽  
Myeloid Cells ◽  
Increased Risk ◽  
Breast Cancer Brain Metastasis ◽  
Metastasis Development ◽  
Effect Of Age ◽  
Young Mice

Abstract Women diagnosed with breast cancer at a younger age (typically defined as < 40 years old) often have a poorer prognosis and an increased risk of brain metastasis compared to their older counterparts. Multivariate analyses accounting for differences in tumor characteristics have shown that age is an independent predictor of worse outcome. We therefore hypothesized that rather than intrinsic tumor properties, extrinsic microenvironmental factors contribute to age-related differences in aggressiveness. The effect of age was examined by injecting brain-selected breast cancer cells into young (2 – 6 months) and older (>12 months) mice. In four brain metastasis models examined, young mice developed 2- to 16-fold (p < 0.05) more brain metastases compared to older mice. The effect of age was not observed in mouse breast cancer models that metastasize to liver and lungs, suggesting that this is an organ-specific phenomenon. Flow cytometry-based immune-profiling of mouse brains showed that T-cells (CD4+, CD8+, and FOXP3+CD25+ regulatory T-cells), monocytes and neutrophils were elevated in brains with metastases, but the abundance of these populations did not vary dramatically with age. Furthermore, antibody-based depletion of T-cells, monocytes and neutrophils did not significantly alter brain metastasis development. Microglia, which are resident CNS myeloid cells, were 1.5-fold more abundant in young brains compared to older brains. Depletion of CNS myeloid cells using the colony stimulating factor-1-receptor inhibitor PLX3397 reduced brain metastatic tumor burden in young mice by 2.1-fold (p < 0.001). Importantly, loss of CNS myeloid cells/microglia, which are normally more activated in aged mice and thus may protect the older brain against metastasis, did not augment brain metastasis formation in older mice. These results suggest that the younger brain is more permissive for breast cancer metastasis and that targeting resident CNS myeloid cells may be an effective strategy to prevent brain metastasis development in younger patients.

scholarly journals A novel panel of differentially-expressed microRNAs in breast cancer brain metastasis may predict patient survival

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Athina Giannoudis ◽  
Kim Clarke ◽  
Rasheed Zakaria ◽  
Damir Varešlija ◽  
Mosavar Farahani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Characteristic Curve ◽  
Differentially Expressed ◽  
Kaplan Meier ◽  
Increased Risk ◽  
Breast Cancer Brain Metastasis ◽  
Differentially Expressed Mirnas ◽  
Metastatic Process ◽  
Met Oncogene

AbstractBreast cancer brain metastasis (BCBM) is an area of unmet clinical need. MicroRNAs (miRNAs) have been linked to the metastatic process in breast cancer (BC). In this study, we aim to determine differentially-expressed miRNAs utilising primary BCs that did not relapse (BCNR, n = 12), primaries that relapsed (BCR) and their paired (n = 40 pairs) brain metastases (BM) using the NanoString™ nCounter™ miRNA Expression Assays. Significance analysis of microarrays identified 58 and 11 differentially-expressed miRNAs between BCNR vs BCR and BCR vs BM respectively and pathway analysis revealed enrichment for genes involved in invasion and metastasis. Four miRNAs, miR-132-3p, miR-199a-5p, miR-150-5p and miR-155-5p, were differentially-expressed within both cohorts (BCNR-BCR, BCR-BM) and receiver-operating characteristic curve analysis (p = 0.00137) and Kaplan-Meier survival method (p = 0.0029, brain metastasis-free survival; p = 0.0007, overall survival) demonstrated their potential use as prognostic markers. Ingenuity pathway enrichment linked them to the MET oncogene, and the cMET protein was overexpressed in the BCR (p < 0.0001) and BM (p = 0.0008) cases, compared to the BCNRs. The 4-miRNAs panel identified in this study could be potentially used to distinguish BC patients with an increased risk of developing BCBM and provide potential novel therapeutic targets, whereas cMET-targeting warrants further investigation in the treatment of BCBM.

Neratinib: the emergence of a new player in the management of HER2+ breast cancer brain metastasis

2020 ◽  
Vol 16 (7) ◽  
pp. 247-254 ◽  
Author(s):  
Azadeh Nasrazadani ◽  
Adam Brufsky
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Brain Metastasis ◽  
Kinase Inhibitor ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Breast Cancer Patients ◽  
Her2 Breast Cancer ◽  
Increased Risk ◽  
Breast Cancer Brain Metastasis

HER2-positive (HER2+) breast cancer has become an effectively treatable disease in the era of targeted therapies, and outcomes have improved such that prognosis of this subtype is demonstrated to be superior to HER2-negative disease. Despite these advances, durable responses in HER2+ metastatic disease are challenged by the increased risk for brain metastasis. Neratinib is an irreversible pan-HER kinase inhibitor that has emerged as an effective agent when combined with capecitabine for the management of HER2+ metastatic breast cancer patients with brain metastasis. The randomized, Phase III, NALA trial compares neratinib plus capecitabine to a currently prevailing regimen of lapatinib plus capecitabine and is provided herein. Analysis of NALA portends meaningful changes on the horizon for the management of HER2+ metastatic breast cancer.

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.

Emerging Drugs for the Treatment of Breast Cancer Brain Metastasis: A Review of Patent Literature

2018 ◽  
Vol 13 (3) ◽  
pp. 348-359 ◽  
Author(s):  
Maricruz Anaya-Ruiz ◽  
Cindy Bandala ◽  
Patricia Martinez-Morales ◽  
Gerardo Landeta ◽  
Rebeca D. Martinez-Contreras ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Breast Cancer Brain Metastasis ◽  
Patent Literature

scholarly journals The Incidence of Brain Metastases Among Patients with Metastatic Breast Cancer: A Systematic Review and Meta-Analysis

2020 ◽  
Author(s):  
Markus Kuksis ◽  
Yizhuo Gao ◽  
William Tran ◽  
Christianne Hoey ◽  
Alex Kiss ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Metastatic Breast Cancer ◽  
Brain Metastases ◽  
Triple Negative ◽  
Screening Program ◽  
Meta Analysis ◽  
Metastatic Breast ◽  
Breast Cancer Brain Metastasis

Abstract Background Patients with metastatic breast cancer (MBC) are living longer, but development of brain metastases often limits their survival. We conducted a systematic review and meta-analysis to determine the incidence of brain metastases in this patient population. Methods Articles published from January 2000 to January 2020 were compiled from four databases using search terms related to: breast cancer, brain metastasis, and incidence. The overall and per patient-year incidence of brain metastases were extracted from studies including patients with HER2+, triple negative, and hormone receptor (HR)+/HER2- MBC; pooled overall estimates for incidence were calculated using random effects models. Results 937 articles were compiled, and 25 were included in the meta-analysis. Incidence of brain metastases in patients with HER2+ MBC, triple negative MBC, and HR+/HER2- MBC was reported in 17, 6, and 4 studies, respectively. The pooled cumulative incidence of brain metastases was 31% for the HER2+ subgroup (median follow-up: 30.7 months, IQR: 24.0 – 34.0), 32% for the triple negative subgroup (median follow-up: 32.8 months, IQR: 18.5 – 40.6), and 15% among patients with HR+/HER2- MBC (median follow-up: 33.0 months, IQR: 31.9 – 36.2). The corresponding incidences per patient-year were 0.13 (95% CI: 0.10 – 0.16) for the HER2+ subgroup, 0.13 (95%CI: 0.09 – 0.20) for the triple negative subgroup, and only 0.05 (95%CI: 0.03 – 0.08) for patients with HR+/HER2- MBC. Conclusion There is high incidence of brain metastases among patients with HER2+ and triple negative MBC. The utility of a brain metastases screening program warrants investigation in these populations.

scholarly journals MiR-211 determines brain metastasis specificity through SOX11/NGN2 axis in triple-negative breast cancer

Oncogene ◽  
2021 ◽  
Author(s):  
Jhih-Kai Pan ◽  
Cheng-Han Lin ◽  
Yao-Lung Kuo ◽  
Luo-Ping Ger ◽  
Hui-Chuan Cheng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Survival Outcomes ◽  
Poor Survival ◽  
Breast Cancer Brain Metastasis ◽  
High Level

AbstractBrian metastasis, which is diagnosed in 30% of triple-negative breast cancer (TNBC) patients with metastasis, causes poor survival outcomes. Growing evidence has characterized miRNAs involving in breast cancer brain metastasis; however, currently, there is a lack of prognostic plasma-based indicator for brain metastasis. In this study, high level of miR-211 can act as brain metastatic prognostic marker in vivo. High miR-211 drives early and specific brain colonization through enhancing trans-blood–brain barrier (BBB) migration, BBB adherence, and stemness properties of tumor cells and causes poor survival in vivo. SOX11 and NGN2 are the downstream targets of miR-211 and negatively regulate miR-211-mediated TNBC brain metastasis in vitro and in vivo. Most importantly, high miR-211 is correlated with poor survival and brain metastasis in TNBC patients. Our findings suggest that miR-211 may be used as an indicator for TNBC brain metastasis.

Sign in / Sign up

Export Citation Format

Share Document