Overexpression of chemokine receptor CXCR4 in cancer specimens following neoadjuvant chemotherapy predicts outcome in patients with locally advanced breast cancer (LABC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10578-10578 ◽  
Author(s):  
N. T. Holm ◽  
K. Byrnes ◽  
M. MacDonald ◽  
F. Abreo ◽  
F. Ampil ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Advanced Breast Cancer ◽  
Chemokine Receptor ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Cancer Recurrence ◽  
Advanced Breast ◽  
Western Blots ◽  
Number Of Patients

10578 Background: Despite significant advances made in the treatment of locally advanced breast cancer (LABC) with neoadjuvant chemotherapy, a significant number of patients continue to die. A molecular predictor to identify those who are at an increased risk for relapse is sorely needed. CXCR4 is a chemokine receptor that has been linked to breast cancer invasion and metastasis. We postulate that CXCR4 overexpression levels in cancer specimens following neoadjuvant chemotherapy predict cancer outcome in patients with LABC. Methods: 54 patients with LABC were prospectively accrued and analyzed. All had neoadjuvant chemotherapy, followed by definitive surgical and adjuvant chemo-radiation therapy. Study homogeneity was maintained by standardized treatment, surveillance, and compliance protocols. A 1 cm 3 cancer from the surgical specimens of each patient was retrieved for analysis. CXCR4 levels were detected using Western blots and results were quantified against 1 μg of HeLa cells (positive controls). CXCR4 expression was defined as low (<6.6 fold) or high (= 6.6 fold). Primary endpoints were cancer recurrence and death. Statistical analysis performed included Kaplan-Meier survival analysis, log-rank test, and Cox proportional hazard model. Results: With a median follow-up of 30 months, patients whose tumors had high CXCR4 overexpression (= 6.6 fold) had a statistically significantly higher incidence of recurrence (p= 0.0009) and cancer-related death (p= 0.0168) than those in the low CXCR4 group (< 6.6 fold). After adjusting for tumor size, nodal status, ER, PR and HER-2 status, the relative risk for recurrence and death in the high CXCR4 group was 27.3-fold (p=0.001; 95% CI: 6.2 to 120.8) and 4.8-fold (p=0.0076; 95% CI: 1.5 to 15.0) higher than those in the low CXCR4 group, respectively. Conclusion: High CXCR4 overexpression in cancer specimens following neoadjuvant chemotherapy was highly predictive of cancer recurrence and cancer death in patients with LABC. No significant financial relationships to disclose.

Circulating tumor cells (CTCs) detection in a randomized phase II trial of neoadjuvant chemotherapy for large operable and locally advanced breast cancer (REMAGUS 02): Preliminary results

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10637-10637 ◽  
Author(s):  
J. Y. Pierga ◽  
C. Mathiot ◽  
J. M. Extra ◽  
P. Tresca ◽  
J. Asselah ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Advanced Breast Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Advanced Breast ◽  
Randomized Phase Ii ◽  
Number Of Patients

10637 Background: The presence of CTCs in blood from metastatic breast cancer patients before first line chemotherapy and persistence of CTCs after initiation of treatment, are predictive of shorter overall survival (Cristofanilli M; et al, 2005, J Clin Oncol 23:1420–1430). CTCs could be used as a surrogate marker. The aim of this study was to determine if CTC were present in the blood of patients who received neoadjuvant chemotherapy (CT) for large operable and locally advanced breast cancer, before initiation of CT (preCT) and at the end of CT before surgery (postCT). Methods: 7.5 ml of blood were obtained on CellSave tube from patients included in an ongoing randomized phase II trial. All patients received 4 cycles of Epirubicin-Cyclophosphamide every 3 weeks followed by 4 cycles of docetaxel associated with or not trastuzumab for HER2 positive patients and with or not celecoxib for HER2 negative patients. CTCs were immunomagnetically separated and fluorescently stained with the CellSearch kit. Cells were classified using the CellSpotter Analyzer as CTCs if they stained positive for DAPI (nuclear dye), and cytokeratin 8, 18 and 19, and if they stained negative for the leucocyte-specific antibody CD45. Results: From 10/2004 to 12/2005, preCT blood samples were obtained in 60 patients, analyzed in 56 for technical reasons. At least one CTC was detected in 15/56 (27%, CI 95%: 15.5–38.5%), 1 to 17 cells per sample (median 1.5). With a threshold of 2 cells, 8/56 (14%, CI 95%: 5–23%) patients were classified positive. At time of analysis, pre CT and post CT samples from the same patient were available for 19 patients. Six had >1 CTC/sample before CT (31.5%) and only one (1/6, 17%) remained positive after CT. Thirteen were negative for CTC before CT and 2/13 (15%) became positive after CT, with only one cell per sample. Conclusions: CTCs can be detected in blood of patients with large operable or locally advanced breast cancer before initiation of neoadjuvant CT and can be monitored during treatment. Longer follow-up and a larger number of patients are expected before correlating these data with tumor response and survival. No significant financial relationships to disclose.

scholarly journals The Prognostic Impact of Body Composition for Locally Advanced Breast Cancer Patients Who Received Neoadjuvant Chemotherapy

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 608
Author(s):  
Toshiaki Iwase ◽  
Aaroh Parikh ◽  
Seyedeh S. Dibaj ◽  
Yu Shen ◽  
Tushaar Vishal Shrimanker ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Composition ◽  
Adipose Tissue ◽  
Neoadjuvant Chemotherapy ◽  
Advanced Breast Cancer ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Advanced Breast

Our previous study indicated that a high amount of visceral adipose tissue was associated with poor survival outcomes in patients with early breast cancer who received neoadjuvant chemotherapy. However, inconsistency was observed in the prognostic role of body composition in breast cancer treatment outcomes. In the present study, we aimed to validate our previous research by performing a comprehensive body composition analysis in patients with a standardized clinical background. We included 198 patients with stage III breast cancer who underwent neoadjuvant chemotherapy between January 2007 and June 2015. The impact of body composition on pathologic complete response and survival outcomes was determined. Body composition measurements had no significant effect on pathologic complete response. Survival analysis showed a low ratio of total visceral adipose tissue to subcutaneous adipose tissue (V/S ratio ≤ 34) was associated with shorter overall survival. A changepoint method determined that a V/S ratio cutoff of 34 maximized the difference in overall survival. Our study indicated the prognostic effect of body composition measurements in patients with locally advanced breast cancer compared to those with early breast cancer. Further investigation will be needed to clarify the biological mechanism underlying the association of V/S ratio with prognosis in locally advanced breast cancer.

scholarly journals Prediction of Chemoresistance in Women Undergoing Neo-Adjuvant Chemotherapy for Locally Advanced Breast Cancer: Volumetric Analysis of First-Order Textural Features Extracted from Multiparametric MRI

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
M. M. Panzeri ◽  
C. Losio ◽  
A. Della Corte ◽  
E. Venturini ◽  
A. Ambrosi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Advanced Breast Cancer ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Volumetric Analysis ◽  
Pathological Response ◽  
Advanced Breast ◽  
Washout Rate ◽  
First Order

Purpose. To assess correlations between volumetric first-order texture parameters on baseline MRI and pathological response after neoadjuvant chemotherapy (NAC) for locally advanced breast cancer (BC). Materials and Methods. 69 patients with locally advanced BC candidate to neoadjuvant chemotherapy underwent MRI within 4 weeks from the start of therapeutic regimen. T2, DWI, and DCE sequences were analyzed and maps were generated for Apparent Diffusion Coefficient (ADC), T2 signal intensity, and the following dynamic parameters: k-trans, peak enhancement, area under curve (AUC), time to maximal enhancement (TME), wash-in rate, and washout rate. Volumetric analysis of these parameters was performed, yielding a histogram analysis including first-order texture kinetics (percentiles, maximum value, minimum value, range, standard deviation, mean, median, mode, skewness, and kurtosis). Finally, correlations between these values and response to NAC (evaluated on the surgical specimen according to RECIST 1.1 criteria) were assessed. Results. Out of 69 tumors, 33 (47.8%) achieved complete pathological response, 26 (37.7%) partial response, and 10 (14.5%) no response. Higher levels of AUCmax (p value = 0.0338), AUCrange (p value = 0.0311), and TME75 (p value = 0.0452) and lower levels of washout10 (p value = 0.0417), washout20 (p value = 0.0138), washout25 (p value = 0.0114), and washout30 (p value = 0.05) were predictive of noncomplete response. Conclusion. Histogram-derived texture analysis of MRI images allows finding quantitative parameters predictive of nonresponse to NAC in women affected by locally advanced BC.

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