Experience With A 22 Molecular Marker Predesigned Tissue Microarray In The Preoperative Setting Of Breast Cancer Treated With Fec-Docetaxel, Comparing Complete Responders With Incomplete Responders, And Incomplete Responders Before And After Treatment

J Gasent Blesa,V Alberola Candel, L Sanchez Verde,M Rodriguez Pinilla, E Adrover Cebrian, M Piris Pinilla

JOURNAL OF CLINICAL ONCOLOGY(2008)

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摘要
22151 Background: Studies with Tissue Microarray (TMA) technology in the preoperative setting of breast cancer have been done using thousands of genes, searching for the most relevant genes associated with complete pathologic response (pCR). We pre-designed a TMA with a short panel of genes and tested in 21 patients treated with FEC-Docetaxel preoperative chemotherapy. Panel genes: p53, NFkB, p16, p27, Cyclin E, Ki-67, VEGFR3 PDGFR, AKT/PKB, ER, PR, C-ERBb2, mTOR, Topo II, MAPK, C-MYC, ECadherin, BRCA1, MLH1, MSH2, CHK1, CHK2 p53. Methods: Median age: 54 Histologies: Ductal 19, Lobular 2.Pre-chemotherapy UICC stages: IIA 8, IIB 3, IIA 7, IIIB 2, IIIC 1. Grade: I 4, II 6, III 11. Total administered Cycles: 115, 18 patients completed 8 planned cycles 8 patients shown pCR (38.1%); 7 patients partial response (33.2%) 4 patients stability (19%), and progression in 2 patients (9.5%). Results: Grade was correlated with E-Cadherin (p=0,016), PDGFR (p=0,026), CHK2 (p=0.054), p53 (p=0.055). T was correlated with mTOR (p=0.026), E-Cadherin (p=0.042), p53 (p=0.053). Nodal infiltration was correlated with Ki-67 (p=0.019), and PDGFR (p=0.049). Stage was correlated with C-MYC (p=0.032). Ki-67 was associated with complete pathologic response (pCR) (p=0.019). Positivity for BRCA1, CHK2, and ERK-P, and negativity for MSH2, were close to signigicance. In patients without pCR, we found increase in the expression for BRCA1, MSH2, ERK, VEFGR3 and mTOR, to be the most relevant. Conclusion: We correlated clinic-pathological data with our TMA, and new relevant associations are described. Ki-67 was significantly associated with pCR, and near significance in some other markers. Variations in the level of expression of: BRCA1, MSH2, ERK, VEGFR, were associated with persistence of disease. Some of our associations lack statistical significance due to the small sample, but may be relevant in view of their correlation with previous clinical experience. To our knowledge, this is the first time that this strategy has been used. We have shown its feasibility, and we are working now to expand this technique. No significant financial relationships to disclose.
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关键词
tissue microarray,breast cancer,incomplete responders,complete responders,preoperative setting,fec-docetaxel
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