scholarly journals Markers of breast cancer stromal fibroblasts in the primary tumour site associated with lymph node metastasis: a systematic review including our case series

2013 ◽  
Vol 33 (6) ◽  
Author(s):  
Maria Aparecida Azevedo Koike Folgueira ◽  
Simone Maistro ◽  
Maria Lucia Hirata Katayama ◽  
Rosimeire Aparecida Roela ◽  
Fiorita Gonzales Lopes Mundim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Extracellular Matrix ◽  
Lymph Node ◽  
Plasminogen Activator ◽  
Prognostic Significance ◽  
Lymph Node Status ◽  
Positive Staining ◽  
Regional Metastasis ◽  
Extracellular Matrix Components

CAFs (cancer-associated fibroblasts), the most abundant cell type in breast cancer stroma, produce a plethora of chemokines, growth factors and ECM (extracellular matrix) proteins, that may contribute to dissemination and metastasis. Axillary nodes are the first metastatic site in breast cancer; however, to the present date, there is no consensus of which specific proteins, synthesized by CAFs, might be related with lymph node involvement. The purpose of this study was to perform a systematic review of CAF biomarkers associated with the presence of regional metastasis. PubMed was searched using the words: ‘breast cancer’ and ‘lymph node’ and fibroblast or stroma or microenvironment. After exclusions, eight studies evaluating biomarkers immunoexpression in CAFs and lymph node status were selected. Biomarkers evaluated in these studies may be divided in two groups, according to their ontology: extracellular matrix components [MMP13 (matrix metalloproteinase 13), TIMP2 (tissue inhibitor of metalloproteinases-2), THBS1 (thrombospondin 1), LGALS1 (lectin, galactoside-binding, soluble, 1)] and response to wounding [PDPN (podoplanin), PLAU (plasminogen activator, urokinase), PLAUR (plasminogen activator, urokinase receptor), CAV1 (caveolin 1), THBS1, LGALS1]. A positive expression of MMP13 and LGALS1 in CAFs was associated with enhanced OR (odds ratio) for regional metastasis. Contrariwise, CAV1 positive staining of fibroblasts was associated with decreased OR for nodal involvement. Expression of MMP13, PDPN and CAV1 was further tested in a new series of 65 samples of invasive ductal breast carcinomas by immunohistochemistry and no association between biomarkers expression in CAFs and nodal status was found. It was suggested that breast cancer subtypes may differentially affect CAFs behaviour. It would be interesting to evaluate the prognostic significance of these biomarkers in CAFs from different tumour types.

Metastatic Tumor Volume and Extranodal Tumor Extension: Clinical Significance in Patients With Stage II Breast Cancer

2015 ◽  
Vol 139 (10) ◽  
pp. 1288-1294 ◽  
Author(s):  
Eva Drinka ◽  
Pamela Allen ◽  
Andrew McBride ◽  
Thomas Buchholz ◽  
Aysegul Sahin
Keyword(s):  
Breast Cancer ◽  
Multivariate Analysis ◽  
Lymph Node ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Metastatic Tumor ◽  
Tumor Burden ◽  
Cancer Center ◽  
Lymph Node Status ◽  
Tumor Extension

Context Lymph node status and the number of lymph node (LN) positive for cancer cells are the most important prognostic factors in breast cancer. Extranodal tumor extension (ENTE) has been used as a histopathologic feature to classify patients into high risk versus low risk for local recurrence. However, in the current era of early detection and systemic therapy, the prognostic significance of ENTE is not as well defined in patients with 1 to 3 LNs positive for cancer. Objective To determine whether the amount of tumor burden in an axillary dissection or the presence of ENTE provides any additional information regarding patient outcome in patents with 1 to 3 positive LN results. Design Clinical and pathologic factors were identified for 456 patients with breast cancer at the University of Texas MD Anderson Cancer Center, Houston, who had pT1 tumors and 1 to 3 LNs positive for cancer and were treated by mastectomy, with or without postmastectomy radiotherapy, between 1978 and 2007. Results Of the 456 patients, 257 (56.4%), 141 (31.6%), and 58 (12.7%) patients had 1, 2, or 3 positive LN results, respectively. Extranodal tumor extension was present in 99 patients (21.7%) and was absent in the remaining 357 cases (78.3%). Seventy-six patients (16.7%) received radiation therapy. Patients had both worse overall survival time and disease-free survival when ENTE was present, regardless of the amount, as long as the treatment era was not included in the multivariate analysis (pre-2000 versus post-2000). However, ENTE was no longer significant on multivariate analysis when the year of treatment was taken into account. Conclusions The number of positive LNs remains an important predictor of survival in patients with 1 to 3 positive LN results, but the prognostic significance of ENTE in this cohort of patients has diminished over time.

Breast Cancer Survival in Relation to the Metastatic Tumor Burden in Axillary Lymph Nodes

2010 ◽  
Vol 28 (17) ◽  
pp. 2868-2873 ◽  
Author(s):  
Yvette Andersson ◽  
Jan Frisell ◽  
Maria Sylvan ◽  
Jana de Boniface ◽  
Leif Bergkvist
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Tumor Cells ◽  
Prognostic Significance ◽  
Axillary Lymph Nodes ◽  
Lymph Node Status ◽  
Axillary Lymph ◽  
Isolated Tumor Cells ◽  
Node Negative ◽  
Survival Difference

Purpose The aim of this study was to determine the prognostic significance of lymph node micrometastases in patients with breast cancer. Patients and Methods Between September 2000 and January 2004, 3,369 patients with breast cancer were included in a prospective cohort. According to their lymph node status, they were classified in the following four groups: 2,383 were node negative, 107 had isolated tumor cells, 123 had micrometastases, and 756 had macrometastases. Median follow-up time was 52 months. Kaplan-Meier estimates and the multivariate Cox proportional hazard regression model were used to analyze survival. Results Five-year cause-specific and event-free survival rates were lower for patients with micrometastases (pN1mi) than for node-negative (pN0) patients (94.1% v 96.9% and 79.6% v 87.1%, respectively; P = .020 and P = .032, respectively). There was no significant survival difference between node-negative patients and those with isolated tumor cells. The overall survival of pN1mi and pN0 patients did not differ. Conclusion This study demonstrates a worse prognosis for patients with micrometastases than for node-negative patients.

Lymph Node Status in the Breast Cancer Patient: Sampling Techniques and Prognostic Significance

2007 ◽  
Vol 42 (4) ◽  
pp. 253-264 ◽  
Author(s):  
Beatriz B. Amaral ◽  
Luise Meurer ◽  
Gary J. Whitman ◽  
Jessica W.T. Leung
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Cancer Patient ◽  
Breast Cancer Patient ◽  
Prognostic Significance ◽  
Lymph Node Status ◽  
Sampling Techniques ◽  
Node Status

Non-sentinel lymph node status and prognosis of the breast cancer patients with micrometastatic sentinel lymph nodes

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11504-e11504
Author(s):  
H. Jinno ◽  
T. Onishi ◽  
M. Takahashi ◽  
M. Sakata ◽  
Y. Kitagawa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Sentinel Lymph Node ◽  
Cancer Patients ◽  
Axillary Lymph Node ◽  
Prognostic Significance ◽  
Lymph Node Status ◽  
Axillary Lymph ◽  
Breast Cancer Patients ◽  
Significant Difference

e11504 Background: Sentinel lymph node biopsy (SLNB) has become a standard therapy for clinically node-negative breast cancer patients and improvements of histopathological and molecular analysis of sentinel lymph node (SLN) have increased the rate of micrometastases identified. However it remains controversial whether to perform axillary lymph node dissection (ALND) for patients with micrometastases in SLNs and their prognostic significance is also a matter of debate. The purpose of this study is to determine the non- sentinel lymph node (NSLN) status and prognosis of the patients with micrometastatic SLNs. Methods: A prospective database of 666 breast cancer patients with the tumor size less than 3cm and clinical negative node, who underwent SLNB from January 2002 to July 2007 at Keio University Hospital was analyzed. SLNs were detected using a combined method of isosulfun blue dye and small-sized technetium-99m-labeled tin colloid. SLNs were diagnosed with standard hematoxylin and eosin (HE) staining and immunohistochemical (IHC) analysis. Results: Micrometastases in SLNs were found in 50 (7.5%) of 666 patients. Twenty nine (58.0%) of 50 patients with micrometastatic SLNs underwent ALND and revealed no NSLN metastasis. Among 21 (42.0%) patients with micrometastatic SLNs who skipped ALND, no axillary lymph node recurrence has been observed in the median follow-up time of 43 months, although 20 patients (95.2%) in 21 patients received adjuvant systemic therapy. There is no significant difference in recurrence free survival between the patients with micrometastatic and negative SLNs (98.0% vs. 95.7%, respectively). Conclusions: These date suggested that it may not be necessary to perform ALND for the patients with micrometastases in SLNs and the presence of micrometastases in SLNs may not be associated with prognosis. No significant financial relationships to disclose.

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