Detection of estrogen receptor in bone marrow from patients with metastatic breast cancer.

1987 ◽  
Vol 5 (11) ◽  
pp. 1779-1782 ◽  
Author(s):  
U Berger ◽  
J L Mansi ◽  
P Wilson ◽  
R C Coombes
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Endocrine Therapy ◽  
Tumor Cells ◽  
Epithelial Membrane Antigen ◽  
Metastatic Breast ◽  
Breast Cancers ◽  
Double Staining ◽  
Primary Tumors ◽  
Er Positive

We devised a method of detecting estrogen receptors (ER) in bone marrow metastases from patients with breast cancer. The method involves a sequential double-staining immunocytochemical technique, with a monoclonal antibody to ER and a polyclonal antibody recognizing epithelial membrane antigen to confirm the epithelial nature of suspected tumor cells. Twenty-seven patients were assessed: ten were found to have ER-positive tumor cells in the bone marrow; ten had ER-negative cells; and the remaining seven patients had no tumor cells in the bone marrow smears. Of the ten patients with ER-positive cells, eight (80%) either had a response to endocrine therapy, implying that they possess ER-positive breast cancers, or had ER-positive primary tumors as determined by the dextran-coated charcoal biochemical assay (DCC). Of the ten patients with ER-negative cells in the bone marrow, eight failed to respond to endocrine therapy. This technique therefore provides a means of predicting which patients will respond to endocrine therapy, and is particularly important in those patients whose ER status is unknown.

scholarly journals Evolution of Estrogen Receptor Status from Primary Tumors to Metastasis and Serially Collected Circulating Tumor Cells

2020 ◽  
Vol 21 (8) ◽  
pp. 2885 ◽  
Author(s):  
Carina Forsare ◽  
Pär-Ola Bendahl ◽  
Eric Moberg ◽  
Charlotte Levin Tykjær Jørgensen ◽  
Sara Jansson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Tumor Progression ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Estrogen Receptor Status ◽  
Metastatic Breast ◽  
Primary Tumors ◽  
Er Positive ◽  
Er Status

Background: The estrogen receptor (ER) can change expression between primary tumor (PT) and distant metastasis (DM) in breast cancer. A tissue biopsy reflects a momentary state at one location, whereas circulating tumor cells (CTCs) reflect real-time tumor progression. We evaluated ER-status during tumor progression from PT to DM and CTCs, and related the ER-status of CTCs to prognosis. Methods: In a study of metastatic breast cancer, blood was collected at different timepoints. After CellSearch® enrichment, CTCs were captured on DropMount slides and evaluated for ER expression at baseline (BL) and after 1 and 3 months of therapy. Comparison of the ER-status of PT, DM, and CTCs at different timepoints was performed using the McNemar test. The primary endpoint was progression-free survival (PFS). Results: Evidence of a shift from ER positivity to negativity between PT and DM was demonstrated (p = 0.019). We found strong evidence of similar shifts from PT to CTCs at different timepoints (p < 0.0001). ER-positive CTCs at 1 and 3 months were related to better prognosis. Conclusions: A shift in ER-status from PT to DM/CTCs was demonstrated. ER-positive CTCs during systemic therapy might reflect the retention of a favorable phenotype that still responds to therapy.

scholarly journals The Emerging Role of ESR1 Mutations in Luminal Breast Cancer as a Prognostic and Predictive Biomarker of Response to Endocrine Therapy

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1894 ◽  
Author(s):  
Irene De Santo ◽  
Amelia McCartney ◽  
Ilenia Migliaccio ◽  
Angelo Di Leo ◽  
Luca Malorni
Keyword(s):  
Breast Cancer ◽  
Endocrine Resistance ◽  
Metastatic Breast ◽  
Predictive Biomarker ◽  
Clinical Findings ◽  
Luminal Breast Cancer ◽  
Breast Cancers ◽  
Er Positive ◽  
Esr1 Mutations

Mutations in the hotspot ligand-binding domain of the estrogen receptor (ER) gene ESR1 have recently been recognized as mechanisms of endocrine resistance in endocrine receptor-positive metastatic breast cancer (MBC). Accumulating data suggest these mutations develop under the selective pressure of endocrine treatments, and are infrequent in untreated ER-positive breast cancers. In vitro studies show that these mutations confer ligand-independent activity, resistance to estrogen deprivation, and relative resistance to tamoxifen and fulvestrant. Post-hoc retrospective and prospective analyses of ESR1 mutations in patients with MBC have consistently found that these mutations are markers of poor prognosis and predict resistance to aromatase inhibitors (AIs). These results warrant further investigation and prospective validation in dedicated studies. Moreover, studies are ongoing to clarify the activity of novel drugs in the context of metastatic endocrine resistant luminal breast cancer harboring ESR1 mutations. In this review, we summarize the pre-clinical and clinical findings defining the characteristics of ESR1 mutant breast cancer, and highlight the potential clinical developments in this field.

Estrogen receptor (ER) status of disseminated tumor cells in the bone marrow of breast cancer patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21013-21013
Author(s):  
F. N. Tanja ◽  
N. Krawczyk ◽  
D. Wallwiener ◽  
S. Becker ◽  
E. Solomayer
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Primary Tumor ◽  
Hormone Receptor ◽  
Primary Breast Cancer ◽  
Disseminated Tumor Cells ◽  
Breast Cancer Patients ◽  
Primary Tumors

21013 Background: The presence of disseminated tumor cells (DTC) in bone marrow (BM) of primary breast cancer patients is associated with poor prognosis. These patients may benefit from adjuvant endocrine therapy since cytotoxic agents are not able to completely eliminate DTCs as previously shown. Only patients with hormone receptor positive breast cancer are eligible for hormonal treatment. The ERa status is routinely defined in primary tumor tissue. However, the ERa status of DTC may differ compared to the primary tumor. Therefore, the aims of this study were (1) to determine the ERa status of DTC in BM of breast cancer patients, (2) and to compare the ERa status of DTC and corresponding primary tumors. Methods: BM aspirates from 251 primary breast cancer patients were included into the study. A double immunofluorescence staining procedure was established for the identification of cytokeratin-positive (CK)/ERa positive cells. ERa status of the primary tumor was immunohistochemically assessed using the same antibody against ERa. Results: In 105 of 251 (42%) breast cancer patients CK-positive cells could be detected in BM. The number of detected cells ranged between 1 and 13 / cells per 2*106 mononuclear cells. Disseminated tumor cells demonstrated ERa positivity in 13 (12%) of these 105 patients. The ERa expression on DTC was heterogeneous in 10 of 13 (79%) patients. Concordance rate of ERa status between primary tumor and DTC was 27%. Only 11 of 83 patients with ER a positive tumors had also ERa positives DTC. Conclusions: (1)The hormone receptor status between primary tumor and corresponding DTC is disconcordant. (2)This discrepancy may explain the rate of non-responders to adjuvant endocrine therapy despite ER-positive primary tumors. (3)These patients may benefit from adjuvant therapy regimens based on antibody strategies or bisphosphonates. No significant financial relationships to disclose.

Effect of general anesthetics on the tumor micro-environment in mouse models of breast cancers of spontaneous metastasis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15503-e15503
Author(s):  
Jun Lin ◽  
Ru Li ◽  
Yujie Huang
Keyword(s):  
Breast Cancer ◽  
Mouse Models ◽  
Lung Metastasis ◽  
Primary Tumor ◽  
Cancer Metastasis ◽  
Metastatic Breast ◽  
Health Concern ◽  
Breast Cancers ◽  
General Anesthetics ◽  
Primary Tumors

e15503 Background: Metastatic breast cancer is a pressing health concern worldwide. Various treatments have been developed but no significant long-term changes in overall survival are observed. Therefore, there is a demand to improve current therapies to treat this disease. Surgical resection of the primary tumors is essential in the treatment. However, accumulating evidence alludes to a role for volatile anesthetics which are used during the surgery in metastatic tumor development, but the mechanism remains largely unknown. We have shown anesthetics exert different effects on lung metastasis in mouse models of breast cancers. This study analyses the effect of general anesthetics in lung microenvironment associated with the increased metastases. Methods: Balb/c mice and NOD-SCID mice were orthotopically implanted with 4T1 cells and MDA-MB-231 cells respectively, in the mammary fat pad to generate primary tumors. Mice were subjected to the tested anesthetic during implantation and/or before and after surgery. Surgical dissection of primary tumor was performed under anesthesia with sevoflurane or an intravenous anesthetic propofol. Survival curve was constructed and analysed. Mice were euthanized to harvest tissues for histology and cell analysis. Results: As we previously reported, surgical dissection of primary tumor in mice under anesthesia with sevoflurane led to significantly more lung metastasis than with propofol in both syngeneic murine 4T1 and xenograft human MDA-MB-231 breast cancer models. Sevoflurane was associated with increased IL6(Li, Huang, & Lin, 2020). Here we show that anesthesia with sevoflurane resulted in changes of stroma composition in the lung, which was reversed by IL6 pathway interruption. Conclusions: Those results contribute to our understanding of effects of sevoflurane on cancer metastasis and suggest a potential therapeutic approach to overcome the risk of general anesthesia. Li, R., Huang, Y., & Lin, J. (2020). Distinct effects of general anesthetics on lung metastasis mediated by IL-6/JAK/STAT3 pathway in mouse models. Nat Commun, 11, 642.

scholarly journals SP140L is differentially expressed in metastasis to lymph nodes in human breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Tumor Cells ◽  
Human Breast Cancer ◽  
Metastatic Breast ◽  
Human Breast ◽  
Primary Tumors ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the brain and the breast resides the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with metastasis to the lymph nodes in human breast cancer. We found that the SP140 nuclear body protein like, encoded by SP140L, was among the genes whose expression was most different in the lymph nodes metastases of patients with metastatic breast cancer as compared to primary tumors of the breast (4). SP140L was also differentially expressed in the tumor cells of patients with triple negative breast cancer (5). SP140L mRNA was present at increased quantities in lymph node metastatic tissues as compared to primary tumors of the breast. Importantly, expression of SP140L in primary tumors was significantly correlated with patient overall survival, in lymph node positive patients but not in lymph node negative patients. Modulation of SP140L expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph node and to the brain in humans with metastatic breast cancer.

scholarly journals CCDC155 is differentially expressed in metastasis to lymph nodes in human breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Tumor Cells ◽  
Human Breast Cancer ◽  
Metastatic Breast ◽  
Human Breast ◽  
Primary Tumors ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). Between the brain and the breast resides the secondary lymphoid organ, the lymph nodes. We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with metastasis to the lymph nodes in human breast cancer. We found that the coiled-coil domain containing 155, encoded by CCDC155, was among the genes whose expression was most different in the lymph nodes metastases of patients with metastatic breast cancer as compared to primary tumors of the breast (4). CCDC155 was also differentially expressed in the tumor cells of patients with triple negative breast cancer (5). CCDC155 mRNA was present at increased quantities in lymph node metastatic tissues as compared to primary tumors of the breast. Importantly, expression of CCDC155 in primary tumors was significantly correlated with patient recurrence-free survival, in lymph node positive patients but in lymph node negative patients. Modulation of CCDC155 expression may be relevant to the biology by which tumor cells metastasize from the breast to the lymph node and to the brain in humans with metastatic breast cancer.

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