Prolonged Stabilization of Multiple and Single Brain Metastases from Breast Cancer with Tamoxifen. Report of Three Cases

1993 ◽  
Vol 79 (5) ◽  
pp. 359-362 ◽  
Author(s):  
Maurizio Salvati ◽  
Luigi Cervoni ◽  
Gualtiero Innocenzi ◽  
Lia Bardella
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Poor Prognosis ◽  
Solitary Lesion ◽  
Therapeutic Trials ◽  
Number Of Patients ◽  
Acceptable Quality ◽  
The Brain ◽  
Sizable Number

Cancer frequently metastasizes to the brain, and such lesions, whether multiple or solitary, have a poor prognosis, despite all efforts to treat them. There have been recent sporadic reports of brain metastases from breast cancer responding for some years to antiestrogens (particularly tamoxifen) or bromocryptine. We report three cases of brain metastasis from cancer – two multiple and one a solitary lesion. The long survival of the patients – two for 5 years and one for 6 years, with more than an acceptable quality of life – should prompt therapeutic trials to test tamoxifen and designed to assess its effects on a sizable number of patients.

scholarly journals A common goal to CARE: Cancer Advocates, Researchers, and Clinicians Explore current treatments and clinical trials for breast cancer brain metastases

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Natalie S. Joe ◽  
Christine Hodgdon ◽  
Lianne Kraemer ◽  
Kristin J. Redmond ◽  
Vered Stearns ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Brain Metastases ◽  
Detection Methods ◽  
Future Research ◽  
Breast Cancer Brain Metastasis ◽  
Patient Advocates ◽  
Breast Cancer Brain Metastases ◽  
The Brain

AbstractBreast cancer is the most commonly diagnosed cancer in women worldwide. Approximately one-tenth of all patients with advanced breast cancer develop brain metastases resulting in an overall survival rate of fewer than 2 years. The challenges lie in developing new approaches to treat, monitor, and prevent breast cancer brain metastasis (BCBM). This review will provide an overview of BCBM from the integrated perspective of clinicians, researchers, and patient advocates. We will summarize the current management of BCBM, including diagnosis, treatment, and monitoring. We will highlight ongoing translational research for BCBM, including clinical trials and improved detection methods that can become the mainstay for BCBM treatment if they demonstrate efficacy. We will discuss preclinical BCBM research that focuses on the intrinsic properties of breast cancer cells and the influence of the brain microenvironment. Finally, we will spotlight emerging studies and future research needs to improve survival outcomes and preserve the quality of life for patients with BCBM.

scholarly journals BSCI-11. STROMAL PLATELET DERIVED GROWTH FACTOR RECEPTOR-β (PDGFRβ) PROMOTES BREAST CANCER BRAIN METASTASIS

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i3-i3
Author(s):  
Katie Thies ◽  
Anisha Hammer ◽  
Blake Hildreth ◽  
Luke Russell ◽  
Steven Sizemore ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Tumor Cells ◽  
Mammary Tumor ◽  
Growth Factor Receptor ◽  
Platelet Derived Growth Factor ◽  
Mammary Tumor Cells ◽  
The Brain

Abstract Stromal platelet-derived growth factor receptor-beta (PDGFRβ) has emerged as an actionable mediator of breast tumor-stromal communication. As a receptor tyrosine kinase, PDGFRβ is activated by its ligand, PDGFB, which is released by neighboring tumor epithelium and endothelium. However, how PDGF signaling mediates breast cancer (BC) initiation, progression, and metastasis remains unclear. To evaluate PDGFRβ in this disease, we developed a mouse model of stromal-specific PDGFRβ activation using the Fsp-cre transgene previously published by our group. Mesenchymal-specific activation of PDGFRβ promotes preferential experimental brain metastasis of PDGFB-expressing mammary tumor cells when injected intravenously and accelerates intracranial tumor growth of these cells. Mammary tumor cells expressing low levels of PDGFB do not exhibit a similar increase in brain metastases in PDGFRβ mutant mice. To our knowledge, this is the first example where genetic manipulation of the stroma leads to an increased incidence of BCBM. Our pre-clinical data suggests that primary breast tumors that express high PDGFB could preferentially metastasize to the brain. To test this in patients, we analyzed PDGFB protein expression in a tissue microarray comprised of HER2-positive and triple negative BC primary tumors. While high PDGFB did not correlate with site-independent metastatic recurrence, it was prognostic of brain metastasis, mirroring our mouse data. Our findings suggest that high primary tumor PDGFB expression defines a subset of BC patients predisposed to brain metastases. These patients may benefit from therapeutic intervention of PDGFRβ signaling. To test this pre-clinically, we treated mice harboring intracranial tumors with the PDGFR-specific inhibitor, crenolanib. Excitingly, crenolanib treatment significantly inhibited the brain tumor burden in these mice. Combined, our findings (1) advocate that primary tumor expression of PDGFB is a novel prognostic biomarker for the development of BCBM and (2) support clinical trial evaluation of PDGFR inhibitors for the prevention and treatment of BCBM.

scholarly journals Risk factors for the development of brain metastases in patients with HER2-positive breast cancer

ESMO Open ◽  
2018 ◽  
Vol 3 (6) ◽  
pp. e000440 ◽  
Author(s):  
Christian Maurer ◽  
Lorraine Tulpin ◽  
Michel Moreau ◽  
Cristina Dumitrescu ◽  
Evandro de Azambuja ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Brain Metastases ◽  
Cox Regression ◽  
Lung Metastases ◽  
Screening Method ◽  
Outcome Analysis ◽  
Asymptomatic Patients ◽  
Number Of Patients ◽  
Positive Breast Cancer

BackgroundPatients with metastatic human epidermal growth factor receptor 2-positive breast cancer (HER2+ BC) frequently experience brain metastases (BM). We aimed to define risk factors for the development of BM in patients with HER2+ BC and to report on their outcome.MethodsThis is a retrospective analysis of patients diagnosed with HER2+ BC between January 2000 and December 2014 at Institut Jules Bordet, Belgium. Statistical analyses were conducted with SAS V.9.4 using Kaplan-Meier method and Cox regression analyses.ResultsA total of 483 patients were included of whom 108 (22.4%) developed metastases and 52 (10.8%) BM. Among 96 metastatic patients without BM at diagnosis, 40 (41.7%) developed BM in the course of their disease. In multivariate analysis, risk factors for the development of BM were age ≤40 years (HR 2.10, 95 % CI 1.02 to 4.36), tumour size >2 cm (HR 4.94, 95% CI 1.69 to 14.47), nodal involvement (HR 3.48, 95% CI 1.47 to 8.25), absence or late start (≥6 months after initial diagnosis) of adjuvant anti-HER2 treatment (HR 3.79, 95% CI 1.52 to 9.43 or HR 2.65, 95% CI 1.03 to 6.82) and the development of lung metastases as first site of relapse (HR 6.97, 95% CI 3.41 to 14.24). Twenty-two patients with HER2+ BC and BM sent to our institute for further treatment were included in the outcome analysis. Asymptomatic patients at the time of BM diagnosis showed a better overall survival than symptomatic patients (HR 0.49, 95% CI 0.25 to 0.94).ConclusionA considerable number of patients with metastatic HER2+ BC will develop BM. Screening of patients with risk factors for BM might lead to early detection and better outcome. However, randomised controlled trials examining the use of MRI as a screening method for BM in patients with metastatic BC are warranted before such an approach can be recommended.

scholarly journals AKT1 is differentially expressed in primary tumors and brain metastases in humans with breast cancer.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
Central Nervous System Metastasis ◽  
Human Breast ◽  
Primary Tumors ◽  
Breast Tissues ◽  
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 report here the differential expression of the protein kinase AKT1 in the primary tumors and brain metastases of humans with breast cancer. AKT1 mRNA was present at significantly increased quantities in brain metastatic tissues as compared to primary tumors of the breast. These data combined suggest that up-regulation of AKT1 is a conserved event, both during transformation of breast tissues and progression to central nervous system metastasis and further point to potential importance of AKT1 modulation during progression of human breast cancer.

scholarly journals MMP13 is differentially expressed and down-regulated in brain metastatic breast cancer.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Brain Metastases ◽  
Metastatic Breast ◽  
Clinical Problem ◽  
Differentially Expressed ◽  
Gene Encoding ◽  
Matrix Metalloproteinase 13 ◽  
The Matrix ◽  
The Brain

Brain metastases are a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to discover genes associated with brain metastasis in patients with brain metastatic breast cancer. We found that the gene encoding the matrix metalloproteinase 13, MMP13, was among the genes most differentially expressed in the brain metastases of patients with brain metastatic breast cancer. MMP13 may be of relevance to the biology underlying metastasis to the brain in humans with metastatic breast cancer. MMP13 now joins MMP14, MMP11 and MMP2 among matrix metalloproteinases we have found to be differentially expressed and down-regulated in the brain metastases of humans with metastatic breast cancer (6-8).

scholarly journals Aquaporin 4 over-expression in metastases to the brain in breast cancer.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Water Channel ◽  
Breast Tumors ◽  
Aquaporin 4 ◽  
Primary Breast Tumor ◽  
Over Expression ◽  
Patients With Cancer ◽  
Public Datasets ◽  
The Brain

Brain metastases affect 10-15% of women with breast cancer (1). Metastasis is the most significant contributor to death in patients with cancer (2). We assessed what genes make brain metastases most different from the breast tumors from which they arose using public datasets (3, 4). The aquaporin 4 (AQP4) water channel (5) was one of the most differentially expressed genes in brain metastases when comparing the transcriptomes of matched tumor and metastasis samples from the brain and breast from 16 patients (2). Analysis of a separate dataset showed demonstrated the same result (4). In both cases, aquaporin 4 was expressed at significantly higher levels in metastases to the brain than in the primary breast tumor. This is the first report of aquaporin 4 differential over-expression in the brain metastases of patients with breast cancer.

scholarly journals FGF12 is differentially expressed in the brain metastases of patients with metastatic breast cancer.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Brain Metastases ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
Normal Breast ◽  
Primary Tumors ◽  
Breast Tissues ◽  
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 fibroblast growth factor 12, encoded by FGF12, was among the genes whose expression was most different in the brain metastases of patients with metastatic breast cancer as compared to normal breast tissues. FGF12 mRNA expression was significantly higher in brain metastatic tissues as compared to primary tumors of the breast. Up-regulation of FGF12 expression may contribute to metastasis of tumor cells from the breast to the brain in humans with metastatic breast cancer.

scholarly journals C1R is differentially expressed in the brain metastases of patients with metastatic breast cancer.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Brain Metastases ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
Normal Breast ◽  
Primary Tumors ◽  
Breast Tissues ◽  
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 complement component 1, r subcomponent, encoded by C1R, was among the genes whose expression was most different in the brain metastases of patients with metastatic breast cancer as compared to normal breast tissues. C1R mRNA was present at significantly reduced quantities in brain metastatic tissues as compared to primary tumors of the breast. Down-regulation of C1R expression may contribute to metastasis of tumor cells from the breast to the brain in humans with metastatic breast cancer.

scholarly journals TTF1 is a differentially expressed gene in both lymph node and brain metastases in human breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Lymph Node ◽  
Brain Metastases ◽  
Differentially Expressed Gene ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
Primary Tumors ◽  
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 for the discovery of genes associated with brain metastasis in humans with metastatic breast cancer. We found that transcription termination factor 1, encoded by TTF1, was among the genes whose expression was most quantitatively different in the brain metastases of patients with metastatic breast cancer. TTF1 mRNA was present at decreased quantities in brain metastatic tissues as compared to primary tumors of the breast. Importantly, expression of TTF1 in primary tumors was significantly correlated with patient distant metastasis-free survival in patients with breast cancer. Modulation of TTF1 expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain. These data are one piece of evidence suggesting a common ancestor or tumor clone for brain and lymph node metastases that originate from the primary tumor, alluding to patterns in developmental origin and migratory pathways through the lymph node in human brain metastatic breast cancer.

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