scholarly journals Diffuse Bone Marrow Metastasis as the Initial Presentation of an Occult Breast Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Frank S. Fan ◽  
Chung-Fan Yang ◽  
Yi-Fen Wang

Introduction. Breast cancer is one of the malignancies which tend to involve the bone marrow, but initial presentation with diffuse bone marrow metastasis from an occult breast cancer is very rare. Prognosis is generally very poor for marrow metastasis from solid tumors except that breast cancer is a treatable disease even in such a dismal condition. Case. A 64-year-old woman’s headache was found to result from diffuse adenocarcinoma metastasis in the bone marrow from an unknown primary site. Intensive immunohistochemistry study of bone marrow biopsy specimen confirmed the disease nature to be an estrogen receptor-positive/human epidermal growth factor receptor 2-negative breast cancer. Mammography and magnetic resonance imaging of breasts revealed a suspicious primary lesion in the right breast. Treatment with tamoxifen alone achieved a sustained response. Discussion. Mucin 1 (MUC1), also known as cancer antigen 15-3 (CA 15-3), facilitates motility and metastatic potential of breast cancer cells. Interleukin-1β (IL-1β) drives breast cancer cell growth and colonization in bone marrow adipose tissue niche. Receptor activator of nuclear factor kappa-B (RANK) and its ligand (RANKL) activate osteoclasts to make a favorable bone marrow microenvironment for tumor cells. Agents against MUC1, IL-1β, and RANKL might be of therapeutic effect for patients like ours.

Medicine ◽  
2017 ◽  
Vol 96 (45) ◽  
pp. e8529 ◽  
Author(s):  
Lulu Liu ◽  
Jingjing Zhang ◽  
Mingtai Chen ◽  
Saisai Ren ◽  
Haihui Liu ◽  
...  

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3644
Author(s):  
Daeun You ◽  
Yisun Jeong ◽  
Sun Young Yoon ◽  
Sung A Kim ◽  
Eunji Lo ◽  
...  

Interleukin-1 (IL1) is a proinflammatory cytokine and promotes cancer cell proliferation and invasiveness in a diversity of cancers, such as breast and colon cancer. Here, we focused on the pharmacological effect of Entelon® (ETL) on the tumorigenesis of triple-negative breast cancer (TNBC) cells by IL1-alpha (IL1A). IL1A enhanced the cell growth and invasiveness of TNBC cells. We observed that abnormal IL1A induction is related with the poor prognosis of TNBC patients. IL1A also increased a variety of chemokines such as CCL2 and IL8. Interestingly, IL1A expression was reduced by the ETL treatment. Here, we found that ETL significantly decreased the MEK/ERK signaling pathway in TNBC cells. IL1A expression was reduced by UO126. Lastly, we studied the effect of ETL on the metastatic potential of TNBC cells. Our results showed that ETL significantly reduced the lung metastasis of TNBC cells. Our results showed that IL1A expression was regulated by the MEK/ERK- and PI3K/AKT-dependent pathway. Taken together, ETL inhibited the MEK/ERK and PI3K/AKT signaling pathway and suppressing the lung metastasis of TNBC cells through downregulation of IL1A. Therefore, we propose the possibility of ETL as an effective adjuvant for treating TNBC.


2020 ◽  
Vol 13 (1) ◽  
pp. 193-199 ◽  
Author(s):  
Takeshi Yamaguchi ◽  
Mariko Masumoto ◽  
Urara Sakurai ◽  
Minoru Nakane

Patients with cancer of unknown primary (CUP) are generally treated with chemotherapy. Bone marrow involvement suggests an advanced stage, and CUP with disseminated carcinomatosis of the bone marrow (DCBM) appears to have a dismal prognosis. However, our case of CUP with DCBM was successfully treated with a sequence of endocrine therapy over a long period. A woman presenting with low back pain was found to have multiple bone metastasis without an identifiable primary tumor on imaging studies. Blood tests revealed anemia and thrombocytopenia. A bone marrow biopsy was performed and showed relatively uniform small cells, strongly positive for estrogen receptor and progesterone receptor expression. We considered chemotherapy to be risky due to bicytopenia and an aromatase inhibitor, letrozole, was initiated. The patient’s symptoms and laboratory findings gradually improved and bone lesions almost disappeared on FDG-PET/CT after 1 year of treatment. After 2 years on letrozole, hemoglobin levels and platelet counts had been gradually decreasing. Although she had no symptoms and no significant changes were observed on a CT scan, disease progression was highly likely. Thus, second-line treatment with fulvestrant and palbociclib was commenced, and hemoglobin levels and platelet counts were restored to within the normal ranges. She currently continues to receive fulvestrant and palbociclib over a year later. CUP complicated with DCBM might be metastatic occult breast cancer, and endocrine therapy can be a valuable treatment option if tumors express hormone receptors.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3904-3904
Author(s):  
Leah A. Marquez-Curtis ◽  
Marcin Wysoczynski ◽  
Mariusz Z. Ratajczak ◽  
Anna Janowska-Wieczorek

Abstract There is increasing evidence that platelets contribute to cancer metastasis, and yet platelet concentrates are frequently transfused to cancer patients to treat thrombocytopenia after chemotherapy. Recently we reported that microvesicles derived from activated platelets (PMV) transfer various surface receptors/adhesion molecules to normal and malignant target cells and modulate their biological responses (Blood2001; 98:3143; Exp Hematol2002; 30:450). In this work, we hypothesized that the interaction of PMV with cancer cells increases their invasive and metastatic potential. PMV were isolated from outdated platelet concentrates and pre-incubated with human breast cancer cell lines (MDA-MB-231, BT-549 and T47D), and the effect of PMV on the invasive/metastatic potential of these cancer cells was evaluated. We determined (i) the transfer of the platelet-derived antigen CD41 to cancer cells and the adhesion of these cells to human umbilical vein endothelial cells (HUVEC), (ii) the expression of matrix metalloproteinases (MMPs) by breast cancer cells and their ability to cross the reconstituted basement membrane Matrigel, (iii) the expression of CXCR4, the cognate receptor of the a-chemokine SDF-1, produced in bone marrow, in these cell lines after incubation with PMV, and (iv) the effects of PMV on the interactions of the tumor cells with stroma. We found that PMV transfer platelet-derived CD41 integrin to the surface of breast cancer cells and promote their adhesion to HUVEC. Preincubation with PMV upregulates the mRNA for MMP-9 and protein secretion in invasive breast cancer cells (MDA-MB-231 and BT-549) and enhances their trans-Matrigel chemoinvasion. PMV also transfer CXCR4 to the surface of the breast cancer cells and stimulate the trans-Matrigel migration of MDA-MB-231 cells towards SDF-1, which was abrogated by AMD3100, a CXCR4 antagonist. Finally we found that PMV increase activation of the latent form of MMP-2 constitutively secreted by fibroblastic cells in co-cultures of tumor cells with bone marrow stroma. Thus, we conclude that PMV may enhance the invasive and metastatic potential of breast cancer cells. Because concentrations of PMV are known to be higher in old platelet concentrates than in fresh ones, we recommend that cancer patients should preferably be transfused with fresh platelet concentrates only.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1001-1001 ◽  
Author(s):  
C. Panabières ◽  
J. Vendrell ◽  
O. Pellé ◽  
X. Rebillard ◽  
S. Riethdorf ◽  
...  

1001 Background: Metastasis is the main cause of cancer-related death. Single disseminated tumor cells (DTC) can be detected by sensitive immunocytochemical and molecular technologies, but it is still unclear whether these cells are viable and biologically active. Methods: We applied a novel enzyme-linked immunospot assay (‘EPISPOT‘) that reveals a fingerprint of specific proteins secreted from single viable epithelial tumor cells. The membrane of ELISPOT plates were coated with monoclonal antibodies against the tumor-associated marker proteins mucin-1 (MUC1) for breast cancer and prostate-specific antigen (PSA) for prostate cancer. In addition, dual fluorescent EPISPOT assays were developed to characterize MUC1+ and PSA+ cells (i.e. CK19, FGF2 secretion). Results: Even in the absence of overt metastases (stage M0), the EPISPOT assay revealed viable tumor cells in the peripheral blood of 65% of prostate cancer patients (n=31) and the bone marrow of 54% of breast cancer patients (n=37). Respective samples from non-carcinoma controls were EPISPOT- negative, whereas 80 to 100% of samples from metastatic patients (stage M1, n=40) were positive. The number of EPISPOT-positive cells in M0-patients ranged from 2 to 197 in the blood of prostate cancer patients and 1 to 262 in the bone marrow of breast cancer patients, while M1- patients showed significantly higher counts (prostate cancer, 1–684; breast cancer, 4–813). Interestingly, subsets of MUC1- or PSA-secreting cells expressed a breast stem cell-like phenotype (MUC1-/CK19+) or secreted FGF-2 as factor relevant for the growth of DTC, respectively. Conclusions: A significant fraction of cancer patients harbor viable and biologically active tumor cells in their blood and bone marrow, even in the absence of overt metastases. The multiparameter EPISPOT assay helps to identify these putative metastatic precursor cells. No significant financial relationships to disclose.


2010 ◽  
Vol 28 (15_suppl) ◽  
pp. e11515-e11515
Author(s):  
L. M. Soares ◽  
D. G. Candido Reis ◽  
R. Dienstmann ◽  
M. D. Gaui ◽  
P. S. Faria ◽  
...  

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