scholarly journals A gene signature predicts response to neoadjuvant chemotherapy in triple-negative breast cancer patients

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Tianzhi Zheng ◽  
Zhiyuan Pang ◽  
Zhao Zhao
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Characteristic Curve ◽  
Complete Response ◽  
Gene Signature ◽  
Differentially Expressed ◽  
Breast Cancer Patients

Abstract Triple-negative breast cancer (TNBC) accounts for approximately 15% of all breast cancer cases. TNBC is highly aggressive and associated with poor prognosis. The present study aimed to compare gene expression between TNBC patients with pathological complete response (pCR) and those with not complete response (nCR) to neoadjuvant chemotherapy. Microarray data of 16 TNBC patients received neoadjuvant chemotherapy were identified from the Gene Expression Omnibus database and 10 patients of them had pCR. We found that 250 coding genes and 155 long noncoding RNAs (lncRNAs) were statistically differentially expressed between patients with pCR and nCR. Receiver operator characteristic curve and area under the curve (AUC) were calculated to assess predictive value of differentially expressed genes. A gene signature of three coding genes and two lncRNA was developed: 2.318*TCF3 + 7.349*CREB1 + 0.891*CEP44 + 0.091*NR_023392.1 + 1.424*NR_048561.1 − 106.682. The gene signature was further validated and had an AUC = 0.829. In summary, we profiled gene expression in pCR patients and developed a gene signature, which was effective to predict pCR among TNBC patients received neoadjuvant chemotherapy.

scholarly journals A Minimal lncRNA-mRNA Signature Predicts Sensitivity to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer

2018 ◽  
Vol 48 (6) ◽  
pp. 2539-2548 ◽  
Author(s):  
Qian Wang ◽  
Chunmei Li ◽  
Peipei Tang ◽  
Runyuan Ji ◽  
Song Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative Breast Cancer ◽  
Noncoding Rna ◽  
Triple Negative ◽  
Characteristic Curve ◽  
Gene Expression Signature ◽  
Receiver Operator Characteristic Curve ◽  
Response Score

Background/Aims: Triple-negative breast cancer (TNBC) is a highly aggressive malignancy that responds in a diverse manner to neoadjuvant chemotherapy (NAC). This study was aimed to uncover an RNA signature in TNBC patients which predicts pathological complete responses (pCR) to NAC by analyzing long noncoding RNA (lncRNA) and coding gene expression. Methods: Microarray datasets from 26 TNBC patients receiving NAC including ten patients showing pCR were obtained from the Gene Expression Omnibus database. Results: A total of 172 coding genes and 84 lncRNAs were differentially expressed between patients achieving pCR and those who did not. Filtering based on the predictive efficacy of response to NAC using receiver operator characteristic curve (ROC) and area under the curve (AUC) shortlisted 23 lncRNAs and 15 coding genes from consideration. Finally, a response score consisting of 1 lncRNA and 2 coding genes was developed: response score = 2.595*BPESC1 – 1.09*WDR72 –1.428*GADD45A – 0.731. The response score had good predictive performance (AUC=0.931, p< 0.01) and at the cut-off of 0.545, the response score had sensitivity and specificity of 0.8 and 0.9, respectively. Conclusion: We propose a simple gene expression signature of only three RNA species could be employed clinically to predict pCR in TNBC patients receiving NAC.

scholarly journals PIK3CA H1047R Mutation Associated with a Lower Pathological Complete Response Rate in Triple-Negative Breast Cancer Patients Treated with Anthracycline-Taxane–Based Neoadjuvant Chemotherapy

2020 ◽  
Vol 52 (3) ◽  
pp. 689-696 ◽  
Author(s):  
Sanxing Guo ◽  
Sibylle Loibl ◽  
Gunter von Minckwitz ◽  
Silvia Darb-Esfahani ◽  
Bianca Lederer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Pathological Complete Response ◽  
Multivariable Analysis ◽  
Complete Response ◽  
Breast Cancer Patients ◽  
Formalin Fixed Paraffin Embedded ◽  
Exon 20

Purpose<i>PIK3CA</i>, encoding for subunit p110a of phosphatidylinositol 3 kinase, is frequently mutated in breast cancer. <i>PIK3CA</i>mutation was predictive for pathological complete response (pCR) in human epidermal growth factor 2 positive breast cancer. This study explores the association of <i>PIK3CA</i> mutation and pCR in triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy.Materials and MethodsA total of 92 patients with TNBC derived from a prospectively randomized phase II trial GeparSixto study (NCT01426880). Exon 9 and exon 20 of <i>PIK3CA</i> mutations were evaluated by using classical Sanger method with formalin-fixed paraffin-embedded tumor tissues.ResultsSeven of 90 tumors (7.8%) were detectable with a <i>PIK3CA</i> H1047R mutation. Overall, <i>PIK3CA</i> H1047R mutation was significantly associated with a lower pCR rate (14.3% vs. 56.6%; odds ratio, 0.128; 95% confidence interval [CI], 0.015 to 1.108; p=0.047). In carboplatin- containing treatment patients, H1047R mutation trended to predict a lower pCR rate (20% vs. 62.5%; p=0.146). In a multivariable analysis, H1047R mutation trended to predict a lower pCR rate (hazard ratio, 0.1; 95% CI, 0.01 to 1; p=0.056).ConclusionTNBC with a <i>PIK3CA</i> H1047R mutation was less likely to achieve pCR after anthracyclinebased neoadjuvant chemotherapy. Development of H1047R mutant selective inhibitors might be helpful to conquer this subtype of breast cancer.

scholarly journals Clinical and genomic assessment of PD-L1 SP142 expression in triple-negative breast cancer

2021 ◽  
Author(s):  
Sung Gwe Ahn ◽  
Seon-Kyu Kim ◽  
Jonathan H. Shepherd ◽  
Yoon Jin Cha ◽  
Soong June Bae ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Checkpoint Inhibitors ◽  
Pathologic Complete Response ◽  
Gene Expression Signature ◽  
Complete Response ◽  
Gene Signature ◽  
Expression Signature

Abstract Purpose The SP142 PD-L1 assay is a companion diagnostic for atezolizumab in metastatic triple-negative breast cancer (TNBC). We strove to understand the biological, genomic, and clinical characteristics associated with SP142 PD-L1 positivity in TNBC patients. Methods Using 149 TNBC formalin-fixed paraffin-embedded tumor samples, tissue microarray (TMA) and gene expression microarrays were performed in parallel. The VENTANA SP142 assay was used to identify PD-L1 expression from TMA slides. We next generated a gene signature reflective of SP142 status and evaluated signature distribution according to TNBCtype and PAM50 subtypes. A SP142 gene expression signature was identified and was biologically and clinically evaluated on the TNBCs of TCGA, other cohorts, and on other malignancies treated with immune checkpoint inhibitors (ICI). Results Using SP142, 28.9% of samples were PD-L1 protein positive. The SP142 PD-L1-positive TNBC had higher CD8+ T cell percentage, stromal tumor-infiltrating lymphocyte levels, and higher rate of the immunomodulatory TNBCtype compared to PD-L1-negative samples. The recurrence-free survival was prolonged in PD-L1-positive TNBC. The SP142-guided gene expression signature consisted of 94 immune-related genes. The SP142 signature was associated with a higher pathologic complete response rate and better survival in multiple TNBC cohorts. In the TNBC of TCGA, this signature was correlated with lymphocyte-infiltrating signature scores, but not with tumor mutational burden or total neoantigen count. In other malignancies treated with ICIs, the SP142 genomic signature was associated with improved response and survival. Conclusions We provide multi-faceted evidence that SP142 PDL1-positive TNBC have immuno-genomic features characterized as highly lymphocyte-infiltrated and a relatively favorable survival.

scholarly journals Triple negative breast cancer subtypes and pathologic complete response rate to neoadjuvant chemotherapy

Oncotarget ◽  
2018 ◽  
Vol 9 (41) ◽  
pp. 26406-26416 ◽  
Author(s):  
Angela Santonja ◽  
Alfonso Sánchez-Muñoz ◽  
Ana Lluch ◽  
Maria Rosario Chica-Parrado ◽  
Joan Albanell ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Response Rate ◽  
Complete Response Rate ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Cancer Subtypes ◽  
Pathologic Complete Response Rate

scholarly journals Response to FEC Chemotherapy and Oncolytic HSV-1 Is Associated with Macrophage Polarization and Increased Expression of S100A8/A9 in Triple Negative Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5590
Author(s):  
Alyssa Vito ◽  
Nader El-Sayes ◽  
Omar Salem ◽  
Yonghong Wan ◽  
Karen L. Mossman
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Macrophage Polarization ◽  
Gene Signature ◽  
Immune Checkpoint Blockade ◽  
Differential Gene ◽  
Microarray Analyses ◽  
Tumor Cell Killing

The era of immunotherapy has seen an insurgence of novel therapies driving oncologic research and the clinical management of the disease. We have previously reported that a combination of chemotherapy (FEC) and oncolytic virotherapy (oHSV-1) can be used to sensitize otherwise non-responsive tumors to immune checkpoint blockade and that tumor-infiltrating B cells are required for the efficacy of our therapeutic regimen in a murine model of triple-negative breast cancer. In the studies herein, we have performed gene expression profiling using microarray analyses and have investigated the differential gene expression between tumors treated with FEC + oHSV-1 versus untreated tumors. In this work, we uncovered a therapeutically driven switch of the myeloid phenotype and a gene signature driving increased tumor cell killing.

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