scholarly journals Early Prediction of Tumor Response to Neoadjuvant Chemotherapy and Clinical Outcome in Breast Cancer Using a Novel FDG-PET Parameter for Cancer Stem Cell Metabolism

2020 ◽  
Vol 10 (3) ◽  
pp. 132
Author(s):  
Chanwoo Kim ◽  
Sang-Ah Han ◽  
Kyu Yeoun Won ◽  
Il Ki Hong ◽  
Deog Yoon Kim

Cancer stem cells (CSCs) contribute to chemoresistance and tumor relapse. By using the distinct metabolic phenotype of CSC, we designed novel PET parameters for CSC metabolism and investigated their clinical values. Patients with breast cancer who underwent 18F-FDG PET/CT before neoadjuvant chemotherapy (NAC) were retrospectively included. We developed a method to measure CSC metabolism using standardized uptake value histogram data. The predictive value of novel CSC metabolic parameters for pathologic complete response (pCR) was assessed with multivariable logistic regression. The association between the CSC parameter and disease-free survival (DFS) was also determined. We identified 82 patients with HER2-positive/triple-negative subtypes and 38 patients with luminal tumors. After multivariable analysis, only metabolic tumor volume for CSC (MTVcsc) among metabolic parameters remained the independent predictor of pCR (OR, 0.12; p = 0.022). MTVcsc successfully predicted pathologic tumor response to NAC in HER2-positive/triple-negative subtypes (accuracy, 74%) but not in the luminal subtype (accuracy, 29%). MTVcsc was also predictive of DFS, with a 3-year DFS of 90% in the lower MTVcsc group (<1.75 cm3) versus 72% in the higher group (>1.75 cm3). A novel data-driven PET parameter for CSC metabolism provides early prediction of pCR after NAC and DFS in HER2-positive and triple-negative subtypes.

2013 ◽  
Vol 31 (29) ◽  
pp. 3623-3630 ◽  
Author(s):  
Gunter von Minckwitz ◽  
Jens Uwe Blohmer ◽  
Serban Dan Costa ◽  
Carsten Denkert ◽  
Holger Eidtmann ◽  
...  

Purpose We investigated disease-free survival (DFS) and overall survival (OS) after response-guided neoadjuvant chemotherapy in patients with early breast cancer. Patients and Methods We treated 2,072 patients with two cycles of docetaxel, doxorubicin, and cyclophosphamide (TAC) and randomly assigned early responders to four (n = 704) or six (n = 686) additional TAC cycles, and early nonresponders to four cycles of TAC (n = 321) or vinorelbine and capecitabine (NX; n = 301) before surgery. Results DFS was longer in early responders receiving TAC × 8 than in those receiving TAC × 6 (hazard ratio [HR], 0.78; 95% CI, 0.62 to 0.97; P = .026), and in early nonresponders receiving TAC-NX than in those receiving TAC × 6 (HR, 0.59; 95% CI, 0.49 to 0.82; P = .001). Exploratory analysis showed that DFS after response-guided chemotherapy (TAC × 8 or TAC-NX) was significantly longer (HR, 0.71; 95% CI, 0.60 to 0.85; P < .003), as was OS (HR, 0.79; 95% CI, 0.63 to 0.99; P = .048), than on conventional chemotherapy (TAC × 6). DFS was longer after response-guided chemotherapy in all hormone receptor–positive tumors (luminal A HR = 0.55, luminal B [human epidermal growth factor receptor 2 (HER2) negative] HR = 0.40, and luminal B [HER2 positive] HR = 0.56), but not in hormone receptor–negative tumors (HER2 positive [nonluminal] HR = 1.01 and triple negative HR = 0.87). Pathologic complete response did not predict these survival effects. pCR predicted an improved DFS in triple-negative (HR = 6.67), HER2-positive (nonluminal; HR 5.24), or luminal B (HER2-negative) tumors (HR = 3.74). Conclusion This exploratory analysis suggests that response-guided neoadjuvant chemotherapy might improve survival and is most effective in hormone receptor–positive tumors. If confirmed, the response-guided approach could provide a clinically meaningful advantage for the neoadjuvant over the adjuvant approach in early breast cancer.


The Breast ◽  
2013 ◽  
Vol 22 (5) ◽  
pp. 691-697 ◽  
Author(s):  
Bas B. Koolen ◽  
Kenneth E. Pengel ◽  
Jelle Wesseling ◽  
Wouter V. Vogel ◽  
Marie-Jeanne T.F.D. Vrancken Peeters ◽  
...  

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11610-e11610
Author(s):  
Noridza Rivera-Rodriguez ◽  
Fernando Cabanillas ◽  
Lesley Lawrenson ◽  
Viviana Negron ◽  
Orestes Antonio Pavia ◽  
...  

e11610 Background: Achieving a pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) has been associated with improved disease free survival (DFS) and overall survival (OS). The Residual Cancer Burden Score (RCB) method is a useful tool that predicts DFS and OS after NAC. We present the results of pts with either triple negative or HER2 positive breast cancer treated with a novel NAC. Methods: 34 pts with localized breast cancer >1 cm with HER2+ (N=19) or triple negative breast cancer (TNBC) (N=15) were treated with this novel regimen consisting first of TEC (docetaxel 75 mg/m2, epirubicin 80 mg/m2, and cyclophosphamide 500 mg/m2) + PEG Filgrastim x 4 cycles. Following the 4th course, TNBC patients received 4 additional TEC cycles if they achieved CR by MRI, or were switched to a non cross-resistant regimen (vinorelbine, bevacizumab, capecitabine) if they had < CR. HER2+ pts received TEC x4 followed by docetaxel + trastuzumab x 4. RCB score was used to measure pathologic response. Pretreament PET scan was done and repeated after course 1 in order to correlate with RCB. Results: Median age was 56 (58 for Her2+ and 49 for TNBC). RCB= 0 (pCR) was achieved in 76%, while only 1 responded poorly (RCB=3). There was no significant difference in the pCR rate between Her2+ and TNBC patients (74% vs 80% respectively), but there was a difference in the rate of pCR without DCIS and invasive cancer between these two (see table, p=0.034). Pts with SUV drop > 5% after 1st TEC had 84% pCR while none with < 5% achieved pCR (p=0.001). Comparison of our results with other NAC regimens reported in the literature is summarized in the table below. Conclusions: This novel chemotherapy approach results in a high pCR rate and RCB 0-1, which have been associated with improved clinical outcomes. Early PET can predict pCR. Although sample size is modest, results are encouraging and deserve further evaluation. Clinical trial information: NCT 00830544. [Table: see text]


Oncotarget ◽  
2018 ◽  
Vol 9 (41) ◽  
pp. 26406-26416 ◽  
Author(s):  
Angela Santonja ◽  
Alfonso Sánchez-Muñoz ◽  
Ana Lluch ◽  
Maria Rosario Chica-Parrado ◽  
Joan Albanell ◽  
...  

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12605-e12605
Author(s):  
Alexander Philipovskiy ◽  
Sumit Gaur ◽  
Karen Chambers ◽  
Roberto Gamez ◽  
Renato Aguilera ◽  
...  

e12605 Background: Triple-negative breast cancer (TNBC) is a heterogeneous subtype of breast cancer (BC) characterized by the absence of targetable receptors. Traditionally, neoadjuvant chemotherapy (NACT) has been used to downstage the tumors and increase the chance for breast-conserving surgery. The pathological complete response (pCR) has been traditionally considering the best predictive marker for the disease recurrence. Patients with residual disease (RD) have a poor prognosis with a high risk of recurrence, and therefore additional chemotherapy was recommended. Therefore it is an important task for clinical researchers to identify markers to predict the individual tumor response to chemotherapy and avoid in patients potentially resistant tumors. Instead, a surgical approach can be used or combined approach with chemotherapy and immunotherapy. It is not clear yet which approach is optimal for those patients with chemotherapy-resistant tumors since there is no clinical data available and no clinical tool that helps predict the individual tumor response. In this study, we examined breast ultrasound(US) images of patients before and after the completion of NACT and correlated with response to chemotherapy. To better understand the biology of resistance to chemotherapy, we also analyzed the gene expression profile of 15 patients with RD after NACT. Methods: In this study, we retrospective analyzed breast US data from 37 Hispanic patients diagnosed with TNBC and treated with NACT. Patients underwent breast US before and after NACT with documentation of clinical complete response (cCR) or clinical residual disease (cRD). Post-operatively, the pathologic response was defined as the absence of tumor cells (pCR) or presence of residual invasive tumor (RD). A multivariable logistic regression model assessed the influence of patient- and tumor-associated covariates as predictors for pCR. Also, we analyzed formalin-fixed paraffin-embedded tumor samples from 15 patients with RD after NACT. Results: Seventeen patients (45.9%) achieved pCR, and twenty (54.1%) had RD after NACT. The most common US findings connected with RD was the deposition of calcium before NACT six (30%) patients. Gene expression analysis of RD samples identified 446 upregulated and 275 downregulated genes. Among commonly upregulated genes related to cancer, we identified GLI1, IGF1, SERPINE1, ATF3, KLK 5; 7, and TUBB2b, and genes belonging to pathways encoding extracellular matrix–related proteins, DNA-damage response proteins, and pathways related to resistance to chemotherapeutic agents such as Taxol. Conclusions: Our data suggested that gene expression profiling in combination with imaging study can be used to identify patients with TNBC potentially resistant to chemotherapy.


Sign in / Sign up

Export Citation Format

Share Document