scholarly journals Flow cytometric assessment of monocyte activation markers and circulating endothelial cells in patients with localized or metastatic breast cancer

2009 ◽  
Vol 76B (2) ◽  
pp. 107-117 ◽  
Author(s):  
David Goodale ◽  
Carolina Phay ◽  
Wendy Brown ◽  
Leslie Gray-Statchuk ◽  
Patricia Furlong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endothelial Cells ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Circulating Endothelial Cells ◽  
Monocyte Activation ◽  
Activation Markers ◽  
Flow Cytometric

Changes in circulating endothelial cells (CEL) in patients receiving trastuzumab for metastatic breast cancer predict response to treatment

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 579-579
Author(s):  
P. Spadaro ◽  
M. Ingemi ◽  
G. Dottore ◽  
G. Toscano ◽  
R. Maisano
Keyword(s):  
Breast Cancer ◽  
Endothelial Cells ◽  
Metastatic Breast Cancer ◽  
Performance Status ◽  
Antiangiogenic Therapy ◽  
Metastatic Breast ◽  
Circulating Endothelial Cells ◽  
Response To Treatment ◽  
Breast Cancer Patients ◽  
Her 2

579 Background: Amplification or overexpression of HER-2/neu has been identified in 10–20% of invasive breast cancers and is associated with shorter overall survival times; furthermore HER-2/neu is a predictive factor with regard to monoclonal antibody therapy with Trastuzumab. The observed association between the overexpression of HER-2/neu and higher VEGF expression indicates that HER-2/neu is involved, at least partly, in the regulation of angiogenesis in human breast cancer. Recently circulating endothelial cells (CECs) have been proposed as a marker of tumor progression and/or a response to antiangiogenic therapy; thus, we have performed a phase II study to explore the correlation between CECs and treatment with Trastuzumab in metastatic breast cancer Methods: 22 women aged ≥ 18 years with histologically proven Her-2-positive, ECOG performance status 0 to 2 who were not eligible for, or who wished to delay receiving chemotherapy received a standard loading dose of Trastuzumab 4 mg/Kg followed by 2 mg/Kg weekly. The weekly maintenance dose was continued until disease progression. A panel of monoclonal antibodies including anti CD45 to exclude hematopoietic cells, anti CD31, CD34, CD36, CD105, CD106, CD133, and KDR and appropriate analysis gates were used to enumerate resting and activated circulating endothelial cells Results: The overall response rate (RC + RP) to treatment was 25% (2 RC + 3RP). In healthy controls (N° 20) mean values of resting and activated CECs were 7.6/μL (4.6 - 11.2/μL) and 1.3/μL (0.1 - 2.4 /μL) respectively. Before treatment with Trastuzuamb the mean resting and activated CECs were 41.1/μL (16.4 - 60.5/μL) and 6.9/μL (5.1 - 8.7/μL). At a first assessment (6 wks) a significant decrease in CECs (p<0.001)was found in patients responding to treatment but not in the patients who did not achieve a remission Conclusions: Our finding has shown that resting and activated CECs are increased in metastatic breast cancer patients and decline during treatment in responding patients, furthermore, these data underline the crucial role of angiogenesis in this setting and support the rationale for a combination of Bevacizumab with Trastuzumab. No significant financial relationships to disclose.

Change in circulating endothelial cells (CEC) predicts progression free survival (PFS) in patients (pts) with hormone receptor positive metastatic breast cancer (MBC) receiving letrozole (L) and bevacizumab (B)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3039-3039 ◽  
Author(s):  
H. S. Rugo ◽  
M. N. Dickler ◽  
T. A. Traina ◽  
J. H. Scott ◽  
D. H. Moore ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Hormone Receptor ◽  
Antiangiogenic Therapy ◽  
Metastatic Breast ◽  
Circulating Endothelial Cells ◽  
Rank Test ◽  
Nucleic Acid Content ◽  
Activation Markers ◽  
Hormone Receptor Positive

3039 Background: Antiangiogenic therapy has demonstrated efficacy in the treatment (tx) of metastatic breast cancer. Mechanism-based biomarkers of antiangiogenic therapy, if clinically validated, offer the potential to optimize this novel therapy. CECs have been proposed as a marker of tumor progression and/or response to antiangiogenic therapy with B. We performed a feasibility study testing B combined with L for the tx of hormone receptor-positive MBC. To explore markers of activity and response, we assayed CECs and circulating tumor cells (CTCs) at weeks (wks) 0 (baseline), 3, 12, and then Q 12 wks. Methods: CECs were defined as CD34/31+, CD45-. Progenitor (CD133+) (CECp) and activation markers (CD106+) were also measured. For CECs, 50 ul of blood was stained with the indicated MAbs; after RBC lysis, flow cytometry (FC) was performed for total CEC and CECp. For CTCs, 20 ml of blood was subjected to immunomagnetic capture using anti-EpCAM ferrofluid, followed by FC for EpCAM, CD45, and nucleic acid content. The log rank test was used to test for significant differences related to response. Results: 32 of 42 pts have been enrolled. As separately reported, prior non-steroidal AI (NSAI) use without progression is permitted; median (med) time on L before start of B was 6 mo (1–52). 28 pts have at least baseline and week 3 CEC and CTC along with clinical response data. Med CEC level at baseline was 10.4 CEC/ul (4–38); the peak value at any time point was 107. CTC levels were much less frequent with a med of 0.3 CTC/ml (0–95, and highest value 1153). An increase in CECs at wk 3 compared to wk 0 predicted worse PFS (p = 0.015). CTCs were ≤ 0.1 at study start in 40% of pts and ≥ 1.0 in only 17%, likely due to length of prior L; change in values at wk 3 did not correlate with PFS in this pretreated group. Conclusions: Consistent with our previous results in a separate trial of B containing treatment in MBC, changes in CEC levels appear to be a biomarker of response/progression on antiangiogenic therapy. CTCs did not reflect response or progression in this population of patients, likely due to lengthy prior exposure to letrozole. Supported in part by Genentech and Novartis. [Table: see text]

Effect of orally administered S-1 on circulating endothelial cells in patients with metastatic breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21052-e21052
Author(s):  
Wakako Tsuji ◽  
Hiroshi Ishiguro ◽  
Takayuki Ueno ◽  
Masakazu Toi
Keyword(s):  
Breast Cancer ◽  
Endothelial Cells ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Circulating Endothelial Cells ◽  
Molar Ratio ◽  
Enzyme Linked Immunosorbent Assay ◽  
Spectrometric Method ◽  
Mass Spectrometric Method ◽  
Angiogenic Activity

e21052 Background: S-1 is an oral cytotoxic preparation combining tegafur, 5-chloro-2, 4-dihydroxypyridine, and potassium oxonate at a molar ratio of 1:0.4:1, respectively. Tegafur is metabolized into 5-fluorouracil (5-FU), γ-butyrolactone (GBL), and γ-hydroxybutyric acid (GHB). GBL and GHB are known to suppress VEGF-mediated angiogenic activity. Circulating endothelial cells (CECs) have been suggested to be useful for predicting response to anti-angiogenic agents. We evaluated the effects of S-1 on CEC counts in patients with metastatic breast cancer. Methods: Patients with metastatic breast cancer received S-1 orally in 28-day cycles. The dose of S-1 was 80-120 mg/day depending on body surface area. Cycles were repeated every 42 days. CEC counts were measured with the CellSearch system (Veridex, LLC Co. Ltd., NJ) on days 1 (before the 1st cycle of S-1), 15, 29, 43 (before the 2nd cycle of S-1), and 85 (before the 3rd cycle of S-1). Plasma GBL and 5-FU levels were measured by a gas chromatographic-mass spectrometric method at one point each on days 1 (before the 1st cycle of S-1), 15 (1 hour after S-1 administration), 43 (before the 2nd cycle of S-1), and 57 (1 hour after S-1 administration). VEGF levels on days 1, 15, 43, and 57 were measured by an enzyme-linked immunosorbent assay. Results: A total of 18 patients were enrolled. Plasma GBL levels on days 15 and 57 were 42.0 ± 16.2 ng/mL and 43.2 ± 10.5 ng/mL, respectively. Both levels exceeded 25.8 ng/mL, the previously reported (Angiogenesis 2001). Both CEC and CD34+CEC levels significantly decreased on day 15, and low levels were maintained low until day 85. Plasma levels of VEGF also decreased similarly, but not significantly. Conclusions: The results of this exploratory study suggest that S-1 not only has cytotoxic effects on tumor tissue, but also anti-angiogenic activity in patients with metastatic breast cancer.

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