Biomarkers detected by proteomic analysis predicts breast cancer response to neoadjuvant chemotherapy

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 669-669
Author(s):  
D. Shen ◽  
J. He ◽  
J. Gornbein ◽  
Z. Chen ◽  
K. F. Faull ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Proteomic Analysis ◽  
Tumor Response ◽  
Classification Tree ◽  
Objective Assessment ◽  
Locally Advanced ◽  
Poor Responders ◽  
Protein Biomarkers ◽  
Response To Neoadjuvant Chemotherapy

669 Background: Neoadjuvant chemotherapy provides an excellent opportunity for objective assessment of treatment-induced tumor response and for studying biomarkers characteristic of therapy-induced tumor responses. Methods: Proteomic analysis of T3/T4 breast cancer was performed in patients with locally advanced breast cancer in a phase II clinical trial. The breast cancer specimen was obtained before and after four cycles of Taxotere/Carboplatin/±Herceptin treatment. Two proteomic approaches, SELDI mass spectrometry and Clontech Ab Microarray 500, were used to screen for protein biomarkers that predict response of breast cancer to chemotherapy. Results: Five tumors with pathologically complete response (pCR) and 29 tumors with various amounts of residual tumors (Non-pCR) were analyzed by SELDI-TOF using the NP 20 chip. The normalized mass signals were compared between pCR vs Non-pCR at each aligned location by Wilcoxon rank sum test. Statistically significant differences were found at 22 m/z locations using a liberal p <0.20 criterion. The best univariate predictor occurred at m/z 14960 (p=0.004), which correctly classified 5/5 pCR spectra (100%) and 24/29 Non-pCR spectra (83%). A multivariate classification tree developed using m/z 14960 and m/z 12138 intensities correctly classified all 34 spectra. Ab microarray analysis was performed on five pCR tumors and in five tumors with the largest residual cancer. The Internal Normalization Ratio (INR) was calculated and used to compare the difference of protein expression between the two groups. Eight differentially expressed protein biomarkers were selected with the criteria of a statistically significant (Student t, p<0.05) expression change of <0.77 or >1.3 fold. Three proteins (Tat-SF1, PYK2 and PTP1B) were higher, and five (E2F2, IL1b, FEN1, CDC37 and ACM1) were lower in tumors with pCR. The unsupervised hierarchical clustering of the 10 samples by these eight proteins completely separated the pCR tumors from the poor responders. Conclusions: Our study suggests that bothSELDImass spectrometry and antibody microarray may be used to predict the tumor response to neoadjuvant chemotherapy. Proteomic analysis may be useful in developing tailored chemotherapy for breast cancer. [Table: see text]

Tumor clearance of technetium 99m-sestamibi as a predictor of response to neoadjuvant chemotherapy for locally advanced breast cancer.

1998 ◽  
Vol 16 (5) ◽  
pp. 1677-1683 ◽  
Author(s):  
A Ciarmiello ◽  
S Del Vecchio ◽  
P Silvestro ◽  
M I Potena ◽  
M V Carriero ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Tumor Response ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Residual Tumor ◽  
Advanced Breast ◽  
Tumor Clearance ◽  
99Mtc Sestamibi ◽  
Response To Neoadjuvant Chemotherapy

PURPOSE Since we have previously shown that the efflux rate of technetium 99m (99mTc) sestamibi, a transport substrate of P-glycoprotein (Pgp), is directly correlated with Pgp levels in untreated breast carcinoma, we tested whether tumor clearance of 9mTc-sestamibi may be predictive of therapeutic response to neoadjuvant chemotherapy in patients with locally advanced breast cancer. PATIENTS AND METHODS Thirty-nine patients with stage III disease, median tumor diameter 5.8 cm (range, 3 to 10) were enrolled onto this prospective clinical trial and underwent 99mTc-sestamibi scan before neoadjuvant chemotherapy. Patients were injected intravenously (i.v.) with 740 MBq of 99mTc-sestamibi; a 15-minute dynamic study was performed, and static planar images were obtained at 0.5, 1, 2, and 4 hours. The time to half clearance of 99mTc-sestamibi was calculated in each patient from decay corrected time-activity curves using a monoexponential fitting. Patients were treated with epirubicin 150 mg/m2 i.v. every 2 weeks for three courses and then underwent surgery within 3 weeks from the completion of chemotherapy. Residual tumor was assessed by pathologic examination of mastectomy specimens. RESULTS Seventeen of 39 patients showed a rapid tumor clearance of 9mTc-sestamibi (time to half clearance [t1/2] < or = 204 minutes) and 15 of these 17 (88%) showed a highly cellular macroscopic residual tumor at histology that indicated lack of tumor response to neoadjuvant chemotherapy. In contrast, only eight of 22 (36%) with prolonged retention of 99mTc-sestamibi (t1/2 > 204 minutes) showed residual macroscopic tumor at histology (Fisher's exact test, P < .01). CONCLUSION A rapid tumor clearance of 99mTc-sestamibi may predict lack of tumor response to neoadjuvant chemotherapy with drugs affected by the multidrug-resistant phenotype in patients with locally advanced breast carcinoma.

scholarly journals Exploratory Analysis of 18F-3’-deoxy-3’-fluorothymidine (18F-FLT) PET/CT-Based Radiomics for the Early Evaluation of Response to Neoadjuvant Chemotherapy in Patients With Locally Advanced Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Lorenzo Fantini ◽  
Maria Luisa Belli ◽  
Irene Azzali ◽  
Emiliano Loi ◽  
Andrea Bettinelli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Tumor Response ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Pathological Response ◽  
Textural Features ◽  
Flt Pet ◽  
Pet Ct ◽  
Response To Neoadjuvant Chemotherapy

PurposeThe objective of this study was to evaluate a set of radiomics-based advanced textural features extracted from 18F-FLT-PET/CT images to predict tumor response to neoadjuvant chemotherapy (NCT) in patients with locally advanced breast cancer (BC).Materials and MethodsPatients with operable (T2-T3, N0-N2, M0) or locally advanced (T4, N0-N2, M0) BC were enrolled. All patients underwent chemotherapy (six cycles every 3 weeks). Surgery was performed within 4 weeks of the end of NCT. The MD Anderson Residual Cancer Burden calculator was used to evaluate the pathological response. 18F-FLT-PET/CT was performed 2 weeks before the start of NCT and approximately 3 weeks after the first cycle. The evaluation of PET response was based on EORTC criteria. Standard uptake value (SUV) statistics (SUVmax, SUVpeak, SUVmean), together with 148 textural features, were extracted from each lesion. Indices that are robust against contour variability (ICC test) were used as independent variables to logistically model tumor response. LASSO analysis was used for variable selection.ResultsTwenty patients were included in the study. Lesions from 15 patients were evaluable and analyzed: 9 with pathological complete response (pCR) and 6 with pathological partial response (pPR). Concordance between PET response and histological examination was found in 13/15 patients. LASSO logistic modelling identified a combination of SUVmax and the textural feature index IVH_VolumeIntFract_90 as the most useful to classify PET response, and a combination of PET response, ID range, and ID_Coefficient of Variation as the most useful to classify pathological response.ConclusionsOur study suggests the potential usefulness of FLT-PET for early monitoring of response to NCT. A model based on PET radiomic characteristics could have good discriminatory capacity of early response before the end of treatment.

Chemotherapy-induced amennorrhea: Predictive markers of response to neoadjuvant chemotherapy in breast cancer.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 281-281
Author(s):  
S. K. Ahn ◽  
H. Moon ◽  
E. Ko ◽  
J. s. Kim ◽  
J. M. You ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Tumor Response ◽  
Locally Advanced Breast Cancer ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Predictive Markers ◽  
Breast Cancer Patients ◽  
Response To Neoadjuvant Chemotherapy

281 Background: There is controversy about the benefit of chemotherapy-induced amenorrhea (CIA) in breast cancer. We investigated significance of CIA after neoadjuvant chemotherapy for predicting response to neoadjuvant chemotherapy in breast cancer patients. Methods: We reviewed the records of 198 premenopausal patients with breast cancer treated with neoadjuvant chemotherapy between January 2005 and December 2010. Chemotherapy-induced amenorrhea (CIA) was defined as serum FSH level ≥40 IU/L after completion of all scheduled neoadjuvant chemotherapy and prior to definitive surgery. Results: Among 198 breast cancer patients, 132 pts (66.7%) developed CIA after neoadjuvant chemotherapy. 156 pts (78%) underwent DA chemotherapy. The age of CIA patients was older than non-CIA patients (41.55±5.55 vs. 38.27± 6.86 years, p=0.001). The incidence of CIA after neoadjuvant chemotherapy was significantly higher in responder group (responder vs. nonresponder: 87 pts (74.4%) vs. 45 pts (55.6%); p=0.006). Additionally, FSH level after all scheduled neoadjuvant chemotherapy was significantly higher in responder group (FSH 56.41±32.41 mIU/ml vs. 45.76±30.31 mIU/ml; p=0.021). In univariate analysis, CIA (p=0.006) and total number of chemotherapy cycle regardless of chemotherapy regimen (p=0.04) were significantly predictive of tumor response. CIA was only significant predictive factor for tumor response after neoadjuvant chemotherapy on multivariate analysis (p=0.012). Conclusions: CIA is independent predictive markers of response to neoadjuvant chemotherapy in locally advanced breast cancer.

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