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Response to Neoadjuvant Chemotherapy in Triple Negative Breast tumors.

ABSTRACT: In a cohort study of 7 women with primary invasive breast cancer, we obtained a tumor specimen before (biopsy) and after (tumorectomy) 4 cycles of NAC with epirubicine and cyclophosphamide, followed by 4 cycles of taxanes. Total RNA was extracted from tumor specimens and the whole transcriptome was quantified with Affymetrix HuGene1.1ST. Molecular functions changing during chemotherapy were searched.

ORGANISM(S): Homo sapiens

PROVIDER: GSE43816 | GEO | 2016/03/24

SECONDARY ACCESSION(S): PRJNA187494

REPOSITORIES: GEO

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Response to Neoadjuvant Chemotherapy in Triple Negative Breast tumors.

Project description:In a cohort study of 7 women with primary invasive breast cancer, we obtained a tumor specimen before (biopsy) and after (tumorectomy) 4 cycles of NAC with epirubicine and cyclophosphamide, followed by 4 cycles of taxanes. Total RNA was extracted from tumor specimens and the whole transcriptome was quantified with Affymetrix HuGene1.1ST. Molecular functions changing during chemotherapy were searched. Whole genome expression of triple negative breast cancer tissues were measured before and after four cycles neoadjuvant chemotherapy

2016-03-24 | E-GEOD-43816 | biostudies-arrayexpress

Molecular Subtype Predicts Response to Neoadjuvant Chemotherapy in Breast Cancer

Project description:In a prospective cohort study of 32 women with primary invasive breast cancer with a measurable lesion, we obtained a tumor specimen by high speed core biopsy before and after 4 cycles of NAC with epirubicine 90mg/m2 and cyclophosphamide 600mg/m2 every 3 weeks, followed by 4 cycles of docetaxel 100mg/m2. Total RNA was extracted from tumor specimens and the whole transcriptome was quantified with Agilent’s 44K single color microarray interrogating 41000 unique human genes. Tumor lesions were ultrasonographically measured to assess response using Sinn criteria. Genes significant different and significant changing during chemotherapy accompanying and predicting response were searched.

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Phase 1 Trial Combining Neoadjuvant Chemotherapy with Chemokine Modulatory Regimen for Triple Negative Breast Cancer

Project description:BACKGROUND. Pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) of triple negative breast cancer (TNBC) predicts long-term outcomes but is achieved only in 30-40% of patients. Higher CTL in the tumor microenvironment (TME) is associated with higher pCR. Combination with anti-PD1 immunotherapy increases pCR but at the cost of immune-related adverse events (irAEs). Our clinical trial using systemic chemokine-modulatory regimen (CKM; rintatolimod [selective TLR3-Ligand], interferon (IFN)-a2b and celecoxib [COX-2 inhibitor]) in patients with metastatic TNBC selectively increased CTL in the TME, providing rationale for its combination with NAC. METHODS. Phase I study NCT04081389 evaluated nine stage I-II TNBC patients who received 3 weeks of paclitaxel with CKM, followed by 9 weeks of paclitaxel alone, standard dose-dense doxorubicin and cyclophosphamide and surgery. Primary endpoint was safety and secondary endpoint included clinical efficacy. RESULTS. Combination treatment was well-tolerated with no dose-limiting toxicities or irAEs. 5/9 patients attained pCR, and 1 patient had micrometastatic disease (ypTmic). Circulating CTLs were decreased (0.12-fold average decrease) with upregulation of IFN-stimulatory and downregulation of CD8 gene signatures in all patients. This was accompanied by increase in CD8b (7.07- fold increase), CD8a/FoxP3 (2.18-fold increase), CCL5 (5.49-fold increase), and CXCL12 (6.06-fold increase) transcripts and multiplex analysis revealed decrease in epithelial and stromal markers with increase in CTL among patients with pCR. CONCLUSION: Combination paclitaxel/CKM regimen was safe, with preliminary indications of promising pCR+ypTmic of 66%.

2024-11-27 | GSE260989 | GEO

Identification of Novel Biomarkers in Pancreatic Tumor Tissue to Predict Response to Neoadjuvant ChemotherapyIdentification of Novel Biomarkers in Pancreatic Tumor Tissue to Predict Response to Neoadjuvant Chemotherapy

Project description:Neoadjuvant chemotherapy (NAC) has been of recent interest as an alternative to upfront surgery followed by adjuvant chemotherapy in patients with pancreatic ductal adenocarcinoma (PDAC). However, a subset of patients does not respond to NAC and may have been better managed by upfront surgery. Hence, there is an unmet need for accurate biomarkers for predicting NAC response in PDAC. This project aimed to identify upregulated proteins in tumor tissue from poor- and good-NAC responders.

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Neoadjuvant chemotherapy alters the genomic landscape and immune microenvironment of breast cancers

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2023-03-31 | GSE197677 | GEO

TP53 signature predicts survival outcome in triple-negative breast cancer with neoadjuvant chemotherapy

Project description:In the study presented here, a consecutively operated, well-defined cohort of 30 triple-negative breast cancer cases with neoadjuvant chemotherapy, followed up more than five years, was used to acquire TP53 signature composed of a total of 33 genes. Combining the response to NAC and the TP53signature score in triple-negative breast cancer was able to predict an unfavorable prognosis.

2021-12-10 | GSE190275 | GEO

PD-1 blockade potentiates neoadjuvant chemotherapy in NSCLC via increasing CD127+ and KLRG1+ CD8 T cells

Project description:The combination of PD-1 blockade with neoadjuvant chemotherapy (NAC) has achieved unprecedented clinical success in non-small-cell lung cancer (NSCLC) compared to NAC alone, but the underlying mechanisms by which PD-1 blockade augments the effects of chemotherapy remain incompletely elucidated. Single-cell RNA sequencing was performed on CD45+ immune cells isolated from surgically resected fresh tumor tissues of seven NSCLC patients receiving NAC or neoadjuvant pembrolizumab and chemotherapy (NAPC). Multiplex fluorescent immunohistochemistry was performed on paired FFPE tissues before and after NAC or NAPC from 65 resectable NSCLC patients, and results were validated with GEO dataset. NAC resulted in an increase only of CD20+ B cells, whereas NAPC increased the infiltration of CD20+ B cells, CD4+ T cells, CD4+CD127+ T cells, CD8+ T cells, CD8+CD127+ and CD8+KLRG1+ T cells. Synergistic increase in B and T cells promotes favorable therapeutic response after NAPC. Spatial distribution analysis discovered that CD8+ T cells and their CD127+ and KLRG1+ subsets were in closer proximity to CD4+ T/CD20+ B cells in NAPC versus NAC. GEO dataset validated that B-cell, CD4, memory and effector CD8 signatures correlated with therapeutic responses and clinical outcomes. The adding of PD-1 blockade to NAC promoted anti-tumor immunity through T and B cells recruitment in the tumor microenvironment and induced tumor-infiltrating CD8+ T cells skewed toward CD127+ and KLRG1+ phenotypes，which may be assisted by CD4+ T cells and B cells. Our comprehensive study identified key immune cell subsets exerting anti-tumor responses during PD-1 blockade therapy and that may be therapeutically targeted to improve upon existing immunotherapies for NSCLC.

2023-05-16 | GSE229353 | GEO

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