Tumor expression data from neoadjuvant trial of cisplatin monotherapy in triple negative breast cancer patients
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE18864 | GEO | 2009/11/04
SECONDARY ACCESSION(S): PRJNA121115
REPOSITORIES: GEO
Similar Datasets
Project description:Evidence suggests that BRCA1 mutation associated tumors have increased sensitivity to DNA damaging agents like cisplatin. Sporadic triple negative breast cancers (TNBC) have many phenotypic similarities to BRCA1 tumors and may have a similar sensitivity to cisplatin. We tested the efficacy of cisplatin monotherapy in 28 TNBC patients in a single arm neoadjuvant trial with outcome measured by pathologic treatment response quantified using the Miller-Payne scale. We used microarrays gene expression profiles to determine tumor subtype of each trial tumor sample and to test various expression signatures for association with pathologic response to cisplatin. Pretreatment tumor samples from the clinical trial (N=24 with adequate tissue) were used for RNA extraction, linear amplification, biotin labeling and hybridization to Affymetrix U133 plus 2.0 arrays. A reference set of 51 primary breast tumors representing all subtypes of breast cancer were processed in a similar manner to include linear amplification, and hybridized to Affymetrix arrays.
2009-11-04 | E-GEOD-18864 | biostudies-arrayexpress
Project description:DNA repair competency is one determinant of sensitivity to certain chemotherapy drugs, such as cisplatin. Cancer cells with intact DNA repair can avoid the accumulation of genome damage during growth and also can repair platinum-induced DNA damage. We sought genomic signatures indicative of defective DNA repair in cell lines and tumors and correlated these signatures to platinum sensitivity. The number of subchromosomal regions with allelic imbalance extending to the telomere (NtAI) predicted cisplatin sensitivity in vitro and pathologic response to preoperative cisplatin treatment in patients with triple-negative breast cancer (TNBC). In serous ovarian cancer treated with platinum-based chemotherapy, higher levels of NtAI forecast a better initial response. We found an inverse relationship between BRCA1 expression and NtAI in sporadic TNBC and serous ovarian cancers without BRCA1 or BRCA2 mutation. Thus, accumulation of telomeric allelic imbalance is a marker of platinum sensitivity and suggests impaired DNA repair. SNP data from 27 and 40 primary triple negative breast cancer tumor samples from two clinical trials treated with cisplatin and cisplatin + bevacizumab. Labeling, hybridization and data processing was performed by Affymetrix using 70k MIP arrays and 330k MIP arrays. In the cisplatin trial, matched normal samples based on blood from all patients and an additional three samples based on FFPE negative lymph nodes were used as references (30 normal references in total). In the cisplatin+bevacizumab trial, mathed normal samples based on blood from 10 patients were used as references.
2012-03-22 | E-GEOD-28330 | biostudies-arrayexpress
Project description:Some triple-negative breast cancer (TNBC) patients evaluated as Miller-Payne 4 with ypN0 after neoadjuvant chemotherapy (NACT) who have better prognosis should avoid escalation of therapy. We aim to identify these patients through evaluating pretherapeutic spatial distributions of immunophenotypes. Our retrospective study in patients with TNBC assessed as Miller-Payne grade 4/5 with ypN0 showed that Miller-Payne 4 with ypN0 group had poorer 5-year disease-free survival (DFS, 63.8% vs 83.0%, p=0.003) and the 5-year overall survival (OS, 71.0% vs 85.5%, p=0.007) than Miller-Payne 5 with ypN0 group. High TILs were significantly associated with better DFS and OS in patients with Miller-Payne 4 and ypN0 (both p=0.016). Spatially, detected by multiplexed ion beam imaging by time of flight combined with proteomics, tumors assessed as Miller-Payne 4 and ypN0 with good prognosis exhibited an inflamed phenotype, with dominant CD8+ T cells on tumor center, few scattered CD68+ myeloid-derived cells far away from T cells, and deposit of increased activated molecules of lymphocyte. While those with poor prognosis presented excluded phenotype, with few CD8+ T cells restricted to invasive margin and a high density of CD14+CD68+CD11c+ myeloid cells. A good classifier model based on 29 spatial immunophenotypes was established by the random forest algorithm (AUC=0.975), for identifying patients with Miller-Payne 4 and ypN0 who had favorable prognosis. We also observed similar signatures in patients with Miller-Payne 5 and ypN0. Taken together, spatial immunophenotypes may assess the prognosis in TNBC patients with Miller-Payne 4 and ypN0 after NACT.
2023-07-08 | PXD029186 | Pride
Project description:The aim of this study was to compare the gene expression profile changes breast tumors after the treatment with Anthracyclines and Taxanes. To this end, an oligonucleotide microarray was performed (AffymetrixM-bM-^@M-^Ys HG-U133 Plus 2.0 array). This gene expression study was carried out on the biopsied tumor samples previous being treated with chemotherapy, and subsequently compared with themselves once treatment schedule ended. The post-chemotherapy biopsy was obtained from the surgical piece. The goal of this study was the finding of several genes related to apoptosis, proliferation, differentiation, survival and transformation-related genes and correlating their differences in expression with the degree of response to chemotherapy, determined by the Miller and Payne histological grading system. After informed consent, patients with a histologically confirmed diagnosis of breast cancer and scheduled chemotherapy treatment based on Anthracyclines and Taxanes (Treatment A: Epirubicin 90 mg/m2-Cyclophosphamide 600 mg/m2, 3 cycles bi-weekly and Paclitaxel 150 mg/m2-Gemcitabine 2500 mg/m2, 6 cycles bi-weekly M-BM-1 weekly Herceptin 4 mg/Kg during the first week, 2 mg/Kg for the remaining 11 cycles; Treatment B: Doxorubicin 60 mg/m2-Pemetrexed 500 mg/m2, 4 cycles tri-weekly and Docetaxel 100 mg/m2, 4 cycles tri-weekly; Treatment C: Doxorubicin 60 mg/m2-Cyclophosphamide 600 mg/m2, 4 cycles tri-weekly and Docetaxel 100 mg/m2, 4 cycles tri-weekly ) were recruited for this study. Pre-chemotherapy and post-chemotherapy biopsies were examined by a pathologist who determined the Miller & Payne grade for each patient. Matching pairs of pre-chemotherapy and post-chemotherpy samples were divided into 3 groups according to Miller & Payne grade: group of bad response (Miller & Payne grades 1 and 2), group of mid response (Miller & Payne grade 3) and group of good response (Miller & Payne grades 4 and 5). Gene expression analysis was performed in paired samples as follows: mid response group post-chemotherapy biopsy vs pre-chemotherapy biopsy (Mid final vs initial). For this assay were necessary 20 samples being chosen according to histopathologic criteria (Miller & Payne grade 3). Other comparisons in which this group of samples was involved include: Initial Good vs Mid, Initial Bad vs Mid, Final Bad vs Mid and Final Good vs Mid. This gene expression profiling was carried out making use of AffymetrixM-bM-^@M-^Ys GeneChip technology, with the AffymetrixM-bM-^@M-^Ys HG-U133 Plus 2.0 array from this provider. All the protocols and apparatus were recommended by Affymetrix. Total RNA from frozen mammary tumors was directly extracted by a RNeasy Mini kit and homogenized by QIAshredder columns under manufacturerM-bM-^@M-^Ys instructions. The quality and quantity of the obtained RNA, was checked out through agarose electrophoresis and later spectrophotometry at 260/280 nm. Biotinylated cRNA was synthesized following the IVT labeling kit from Affymetrix and purified by the GeneChip Sample Cleanup Module from Affymetrix. Once again, the quality and quantity of the obtained cRNA, was checked out through agarose electrophoresis and posterior spectrophotometry at 260/280 nm. After hybridization, slides were washed and scanned following the manufacturerM-bM-^@M-^Ys standard protocol. Intensity values were normalized by Robust Multichip Average method and subsequently these were filtered for remove the control sequences and those with a hybridization signal near to background. The spike controls were: BioB, BioC, BioD and Cre; because BioB was the less presented in the samples, it was used to estimate the sensitivity of the experiment. The housekeeping control was GAPDH. After non-supervised PCA analysis and clustering, gene expression statistical significances were identified by two regression models taking into account the pathologic response to chemotherapy and if the sample was obtained before or after chemotherapy treatment. Supervised PCA analysis and clustering were performed with processed data. Partek Genomics Suite v7.3.1 (Partek) software was employed for the statistic analysis and clustering.
2012-12-12 | E-GEOD-28583 | biostudies-arrayexpress
Project description:The aim of this study was to compare the gene expression profile changes breast tumors after the treatment with Anthracyclines and Taxanes. To this end, an oligonucleotide microarray was performed (AffymetrixM-bM-^@M-^Ys HG-U133 Plus 2.0 array). This gene expression study was carried out on the biopsied tumor samples previous being treated with chemotherapy, and subsequently compared with themselves once treatment schedule ended. The post-chemotherapy biopsy was obtained from the surgical piece. The goal of this study was the finding of several genes related to apoptosis, proliferation, differentiation, survival and transformation-related genes and correlating their differences in expression with the degree of response to chemotherapy, determined by the Miller and Payne histological grading system. After informed consent, patients with a histologically confirmed diagnosis of breast cancer and scheduled chemotherapy treatment based on Anthracyclines and Taxanes (Treatment A: Epirubicin 90 mg/m2-Cyclophosphamide 600 mg/m2, 3 cycles bi-weekly and Taxol 150 mg/m2-Gemcitabine 2500 mg/m2, 6 cycles bi-weekly M-BM-1 weekly Herceptin 4 mg/Kg during the first week, 2 mg/Kg for the remaining 11 cycles; Treatment B: Doxorubicin 60 mg/m2-Pemetrexed 500 mg/m2, 4 cycles tri-weekly and Taxotere 100 mg/m2, 4 cycles tri-weekly; Treatment C: Doxorubicin 60 mg/m2-Cyclophosphamide 600 mg/m2, 4 cycles tri-weekly and Taxotere 100 mg/m2, 4 cycles tri-weekly) were recruited for this study. Pre-chemotherapy and post-chemotherapy biopsies were examined by a pathologist who determined the Miller & Payne grade for each patient. Matching pairs of pre-chemotherapy and post-chemotherapy samples were divided into 3 groups according to Miller & Payne grade: group of bad response (Miller & Payne grades 1 and 2), group of mid response (Miller & Payne grade 3) and group of good response (Miller & Payne grades 4 and 5). Gene expression analysis was performed in paired samples as follows: bad response group post-chemotherapy biopsy vs pre-chemotherapy biopsy (Bad Final vs Initial). For this assay were necessary 13 samples being chosen according to histopathologic criteria (Miller & Payne grades 4 and 5). Of them, 10 samples were paired and 3 pre-chemotherapy samples from patients that experienced a good response to chemotherapy were also included in this experimental series. Other comparisons in which this group of samples was involved include: Initial Bad vs Good, Initial Good vs Mid, Final Mid vs Good and Final Bad vs Good. This gene expression profiling was carried out making use of AffymetrixM-bM-^@M-^Ys GeneChip technology, with the AffymetrixM-bM-^@M-^Ys HG-U133 Plus 2.0 array from this provider. All the protocols and apparatus were recommended by Affymetrix. Total RNA from frozen mammary tumors was directly extracted by a RNeasy Mini kit and homogenized by QIAshredder columns under manufacturerM-bM-^@M-^Ys instructions. The quality and quantity of the obtained RNA, was checked out through agarose electrophoresis and later spectrophotometry at 260/280 nm. Biotinylated cRNA was synthesized following the IVT labeling kit from Affymetrix and purified by the GeneChip Sample Cleanup Module from Affymetrix. Once again, the quality and quantity of the obtained cRNA, was checked out through agarose electrophoresis and posterior spectrophotometry at 260/280 nm. After hybridization, slides were washed and scanned following the manufacturerM-bM-^@M-^Ys standard protocol. Intensity values were normalized by Robust Multichip Average method and subsequently these were filtered for remove the control sequences and those with a hybridization signal near to background. The spike controls were: BioB, BioC, BioD and Cre; because BioB was the less presented in the samples, it was used to estimate the sensitivity of the experiment. The housekeeping control was GAPDH. After non-supervised PCA analysis and clustering, gene expression statistical significances were identified by two regression models taking into account the pathologic response to chemotherapy and if the sample was obtained before or after chemotherapy treatment. Supervised PCA analysis and clustering were performed with processed data. Partek Genomics Suite v7.3.1 (Partek) software was employed for the statistic analysis and clustering.
2012-12-12 | E-GEOD-28694 | biostudies-arrayexpress
Project description:The aim of this study was to compare the gene expression profile changes breast tumors after the treatment with Anthracyclines and Taxanes. To this end, an oligonucleotide microarray was performed (AffymetrixM-bM-^@M-^Ys HG-U133 Plus 2.0 array). This gene expression study was carried out on the biopsied tumor samples previous being treated with chemotherapy, and subsequently compared with themselves once treatment schedule ended. The post-chemotherapy biopsy was obtained from the surgical piece. The goal of this study was the finding of several genes related to apoptosis, proliferation, differentiation, survival and transformation-related genes and correlating their differences in expression with the degree of response to chemotherapy, determined by the Miller and Payne histological grading system. After informed consent, patients with a histologically confirmed diagnosis of breast cancer and scheduled chemotherapy treatment based on Anthracyclines and Taxanes (Treatment A: Epirubicin 90 mg/m2-Cyclophosphamide 600 mg/m2, 3 cycles bi-weekly and Taxol 150 mg/m2-Gemcitabine 2500 mg/m2, 6 cycles bi-weekly M-BM-1 weekly Herceptin 4 mg/Kg during the first week, 2 mg/Kg for the remaining 11 cycles; Treatment B: Doxorubicin 60 mg/m2-Pemetrexed 500 mg/m2, 4 cycles tri-weekly and Taxotere 100 mg/m2, 4 cycles tri-weekly; Treatment C: Doxorubicin 60 mg/m2-Cyclophosphamide 600 mg/m2, 4 cycles tri-weekly and Taxotere 100 mg/m2, 4 cycles tri-weekly ) were recruited for this study. Pre-chemotherapy and post-chemotherapy biopsies were examined by a pathologist who determined the Miller & Payne grade for each patient. Matching pairs of pre-chemotherapy and post-chemotherapy samples were divided into 3 groups according to Miller & Payne grade: group of bad response (Miller & Payne grades 1 and 2), group of mid response(Miller & Payne grade 3) and group of good response (Miller & Payne grades 4 and 5). Gene expression analysis was performed in paired samples as follows: bad response group post-chemotherapy biopsy vs pre-chemotherapy biopsy (Bad Final vs Initial). For this assay were necessary 28 samples being chosen according to histopathologic criteria (Miller & Payne grades 1 and 2). Of them, 26 samples were paired, 1 pre-chemotherapy sample and 1 post-chemotherapy sample from patients that experienced a bad response to chemotherapy were also included in this experimental series. Other comparisons in which this group of samples was involved include: Initial Bad vs Good, Initial Bad vs Mid, Final Bad vs Good and Final Bad vs Mid. This gene expression profiling was carried out making use of AffymetrixM-bM-^@M-^Ys GeneChip technology, with the AffymetrixM-bM-^@M-^Ys HG-U133 Plus 2.0 array from this provider. All the protocols and apparatus were recommended by Affymetrix. Total RNA from frozen mammary tumors was directly extracted by a RNeasy Mini kit and homogenized by QIAshredder columns under manufacturerM-bM-^@M-^Ys instructions. The quality and quantity of the obtained RNA, was checked out through agarose electrophoresis and later spectrophotometry at 260/280 nm. Biotinylated cRNA was synthesized following the IVT labeling kit from Affymetrix and purified by the GeneChip Sample Cleanup Module from Affymetrix. Once again, the quality and quantity of the obtained cRNA, was checked out through agarose electrophoresis and posterior spectrophotometry at 260/280 nm. After hybridization, slides were washed and scanned following the manufacturerM-bM-^@M-^Ys standard protocol. Intensity values were normalized by Robust Multichip Average method and subsequently these were filtered for remove the control sequences and those with a hybridization signal near to background. The spike controls were: BioB, BioC, BioD and Cre; because BioB was the less presented in the samples, it was used to estimate the sensitivity of the experiment. The housekeeping control was GAPDH. After non-supervised PCA analysis and clustering, gene expression statistical significances were identified by two regression models taking into account the pathologic response to chemotherapy and if the sample was obtained before or after chemotherapy treatment. Supervised PCA analysis and clustering were performed with processed data. Partek Genomics Suite v7.3.1 (Partek) software was employed for the statistic analysis and clustering.
2012-12-12 | E-GEOD-28826 | biostudies-arrayexpress
Project description:Germline mutations in BRCA1 or BRCA2 exist in approximately 7% of patients diagnosed with breast cancer and are associated with defects in homologous recombination repair, which has led to the approval of PARP inhibitors for treatment of these cancers in the advanced setting. We have previously reported a phase II neoadjuvant trial of single agent talazoparib for patients with germline BRCA pathogenic variants with a pathologic complete response (pCR) rate of 53%. However, nearly half of the patients treated did not have pCR, thus better strategies are needed to overcome treatment resistance, as well as to identify tumors likely to respond to therapy. To this end, we conducted multi-omic analysis of 13 treatment naïve breast cancer tumors from patients that went on to receive single-agent neoadjuvant talazoparib. We looked for biomarkers that were predictive of response (assessed by residual cancer burden) after 6 months of therapy. We found that all resistant tumors exhibited either the loss of SHLD2, expression of a hypoxia signature, or expression of a stem cell signature. These results indicate that the underlying biology of pre-treatment tumors contain activities that are predictive of response to talazoparib and potentially other PARP inhibitors, and provides a framework that will allow for the better selection of patients for treatment, as well as a roadmap for the development of novel therapies to overcome resistance.
2022-04-30 | GSE160568 | GEO
Project description:Chemotherapy is still the standard–of-care for triple-negative breast cancers (TNBCs). Here, we investigated miR-302b as therapeutic tool to enhance cisplatin sensitivity in vivo and unraveled the molecular mechanism. Material and method: TNBC xenografted mice were treated with miR-302b or control, alone or with cisplatin. Genome-wide transcriptome analysis and independent-validation of ITGA6 expression was assessed on mice tumor samples. SiRNA-knockdown of ITGA6 was performed to evaluate cisplatin response in vitro. Further, potential transcription factors of ITGA6 (E2F1, E2F2 and YY1) were explored to define the miRNA molecular mechanism. MiR-302b expression was also assessed in TNBC patients treated with chemotherapy. Results: MiR-302b-cisplatin combination significantly impaired tumor growth versus control, through indirect ITGA6 downregulation. Indeed, ITGA6 was downmodulated in mice treated with miR-302b-cisplatin and ITGA6 silencing increased drug sensitivity in TNBC cells. In silico analyses and preclinical assays pointed out the regulatory role of E2F family and YY1 on ITGA6 expression under miR-302b-cisplatin treatment. Finally, miR-302b enrichment correlates with better overall survival in 118 TNBC patients. Conclusion: MiR-302b can be exploited as a new therapeutic tool to improve the response to chemotherapy, modulating E2F family, YY1 and ITGA6 expression. Moreover, miR-302b could be defined as new prognostic factor in TNBC patients.
2020-08-21 | GSE152322 | GEO
Project description:We have studied in vivo responses of spontaneous Brca1- and p53-deficient mouse mammary tumors to treatment with doxorubicin, docetaxel or cisplatin.
2007-06-18 | E-NCMF-5 | biostudies-arrayexpress
Project description:Tamoxifen resistance has been a major clinical problem and is accountable for relapse in about one third of ER positive breast cancer patients. Most of the recurrent patients will eventually receive chemotherapy. However, the chemosensitivity of these tamoxifen-resistant breast cancer patients has never been explored. In this study, we demonstrate that tamoxifen-resistant breast cancer cells express significantly more BARD1 and BRCA1, which results in the resistance to DNA-damaging chemotherapy including cisplatin and adriamycin , but not to paclitaxel. Silencing BARD1 or BRCA1 expression or inhibition of BRCA1 phosphorylation by Dinaciclib restored the sensitivity to cisplatin in tamoxifen-resistant cells. In addition, we identified that activated PI3K/AKT pathway in tamoxifen-resistant cells was responsible for the upregulation of BARD1 and BRCA1. PI3K inhibitors, BKM120 and BYL719, decreased the expression of BARD1 and BRCA1 in tamoxifen-resistant cells and re-sensitized them to cisplatin both in vitro and in xenografted mice. Higher BARD1 and BRCA1 expression was associated with poor prognosis of early breast cancer patients, especially the ones received radiotherapy, indicating the potential use of PI3K inhibitors to reverse chemoresistance and radioresistance in ER positive breast cancer patients.
2021-03-15 | GSE111926 | GEO