Serial gene expression analysis in locally advanced breast cancer patients who failed to respond to neoadjuvant chemotherapy
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE32603 | GEO | 2015/06/12
SECONDARY ACCESSION(S): PRJNA147177
REPOSITORIES: GEO
Similar Datasets
Project description:To elucidate candidate genes and pathways associated with poor response, we retrospectively analyzed gene expression profiles in serial biopsies from women with locally advanced breast cancer who failed to respond to anthracycline-based chemo followed by taxane in the I-SPY Of the 221 patients who completed neoadjuvant chemotherapy, 215 patients had surgery with 73% not achieving a pathologic complete response (pathCR). In these patients, cDNA microarray expression profiles from pretreatment biopsy (T1) were compared to those biopsy specimens obtained 24-72 hours after initiation of treatment (T2) or in tumors surgically removed after chemotherapy (TS). Paired expression data for T1vsT2 and T1vsTS were available for 29 and 39 patients with no pathCR, respectively. Paired differential expression analyses were performed via Significance Analysis of Microarrays (SAM) and differentially expressed genes were subjected to Ingenuity Pathway Analysis
2015-06-12 | E-GEOD-32603 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE25055: Discovery cohort for genomic predictor of response and survival following neoadjuvant taxane-anthracycline chemotherapy in breast cancer GSE25065: Validation cohort for genomic predictor of response and survival following neoadjuvant taxane-anthracycline chemotherapy in breast cancer Refer to individual Series
2011-05-11 | E-GEOD-25066 | biostudies-arrayexpress
Project description:Annexin 6 (ANXA6) is a calcium-binding, membrane-associated protein involved in membrane trafficking and cell signalling. Furthermore, ANXA6 has been recently associated to cancer progression and metastasis. The goal of the project was to assess the content of ANXA6 in EVs isolated from the plasma of 6 breast cancer patients undergoing anthracycline/taxane-based neoadjuvant chemotherapy.
2019-01-02 | PXD010292 | Pride
Project description:PURPOSE: To develop a predictive test for response and survival following neoadjuvant taxane-anthracycline chemotherapy for HER2-negative invasive breast cancer. METHODS: We developed a microarray-based gene expression test from pre-treatment tumor biopsies (310 patients) to predict favorable outcome based on estrogen receptor (ER) status,pathologic response to chemotherapy, 3-year disease outcomes, and sensitivity to endocrine therapy. Tumors were classified as treatment-sensitive if predicted to have pathologic response (and not resistance) to chemotherapy, or sensitive to endocrine therapy. We tested predictive accuracy, with 95% confidence interval (CI), for pathologic response (PPV, positive predictive value), distant relapse-free survival (DRFS), and absolute risk reduction at median follow-up in 198 other patients. Independence from clinical-pathologic factors was assessed in a multivariate Cox regression analysis based on the likelihood ratio test. Other evaluable, published response predictors (genomic grade index (GGI), intrinsic subtype (PAM50), pCR predictor (DLDA30)) were compared. Neoadjuvant validation cohort of 198 HER2-negative breast cancer cases treated with taxane-anthracycline chemotherapy pre-operatively and endocrine therapy if ER-positive. Response was assessed at the end of neoadjuvant treatment and distant-relapse-free survival was followed for at least 3 years post-surgery.
2011-05-11 | E-GEOD-25065 | biostudies-arrayexpress
Project description:PURPOSE: To develop a predictive test for response and survival following neoadjuvant taxane-anthracycline chemotherapy for HER2-negative invasive breast cancer. METHODS: We developed a microarray-based gene expression test from pre-treatment tumor biopsies (310 patients) to predict favorable outcome based on estrogen receptor (ER) status,pathologic response to chemotherapy, 3-year disease outcomes, and sensitivity to endocrine therapy. Tumors were classified as treatment-sensitive if predicted to have pathologic response (and not resistance) to chemotherapy, or sensitive to endocrine therapy. We tested predictive accuracy, with 95% confidence interval (CI), for pathologic response (PPV, positive predictive value), distant relapse-free survival (DRFS), and absolute risk reduction at median follow-up in 198 other patients. Independence from clinical-pathologic factors was assessed in a multivariate Cox regression analysis based on the likelihood ratio test. Other evaluable, published response predictors (genomic grade index (GGI), intrinsic subtype (PAM50), pCR predictor (DLDA30)) were compared. Neoadjuvant study of 310 HER2-negative breast cancer cases treated with taxane-anthracycline chemotherapy pre-operatively and endocrine therapy if ER-positive. Response was assessed at the end of neoadjuvant treatment and distant-relapse-free survival was followed for at least 3 years post-surgery.
2011-05-11 | E-GEOD-25055 | biostudies-arrayexpress
Project description:Baseline array profiling data from 46 early breast cancer patients All patients were treated with neoadjuvant anthracycline/anthracycline-taxane regimens
2021-09-30 | GSE180295 | GEO
Project description:To explore novel lncRNAs relative to chemo-resistance in breast cancer, we performed lncRNA microarray analysis using three anthracycline-resistant tissues and three anthracycline-sensitive tissues collected before neoadjuvant chemotherapy by Arraystar Human LncRNA Microarray V3.0.
2024-07-16 | GSE221060 | GEO
Project description:BACKGROUND:We aim to investigate the utility of serial gene mutation tracking for locally advanced CRC in those who underwent curative resection following neoadjuvant chemotherapy. METHODS:We prospectively collected 10 locally advanced CRC cases for which curative resection was performed following preoperative neoadjuvant chemotherapy. Tissues from the primary tumour, distant metastatic tumours, and blood plasma were obtained during serial treatment. Comprehensive mutation analysis of 47 cancer-associated genes was performed using a pre-designed gene panel and next-generation sequencing. RESULTS:All cases showed a partial response to neoadjuvant chemotherapy, and pathological R0 resection was accomplished. In primary tumours, non-synonymous mutations were detected at between 1 and 14 sites before chemotherapy and at between 1 and 2 sites after. Founder mutations were precisely detected in blood plasma and metastatic tumours during longitudinal treatment. CONCLUSIONS:Serial mutational analysis indicated that subclonal selection occurs during chemotherapy and that plasma can substitute for tumourous tissue in mutational analysis for drug selection and treatment decisions.
| S-EPMC6134007 | biostudies-other
Project description:Introduction: The I-SPY 1 TRIAL was designed to evaluate complete pathologic response and tumor volume change, measured by magnetic resonance imaging (MRI), stratified by molecular subtypes and link response to 3-year recurrence free survival (RFS).Methods: Eligible patients had T =3 cm and received neoadjuvant chemotherapy with AC plus optional taxane. Serial MRI, biopsy, and blood draws were conducted over the course of treatment, and a database of multiple molecular profiles was assembled.Results: A total of 221 patients were eligible for analysis: median tumor size was 6.0 cm and median age was 49 years. The I-SPY 1 TRIAL patients had tumors with aggressive biology: 45% were estrogen receptor (ER) negative, 31% Her2+; and 91% high risk by the Netherlands Cancer Institute (NKI) 70-gene profile. After a median of 3.9 years, RFS was 77%. HR/HER2 status improved predictability of RFS with the greatest difference between HR+/HER2- and triple-negative disease (hazard ratio 0.39). Wound healing signature activation, p53 mutation, and Risk of Relapse (ROR) score were highly correlated and also significantly improved the accuracy of RFS predictions when added to stage. The rate of pathologic complete response (pCR) varied considerably from a low of 0-2% (NKI low risk, luminal A) to a high of 43-61% (17q Amplified, HER2 enriched, HR-/HER2+). Both pCR and the more refined residual cancer burden (RCB) were significant predictors of RFS for all patients and even more predictive when analyzed within biomarker subsets. Good risk (NKI low, ROR-S low risk, Wound Healing quiescent, p53 wild type) signatures were associated with significantly higher 3-year RFS than poor risk expression signatures (ROR-S high risk, Wound Healing Activated, p53 mutation, NKI high risk).Conclusion: Importantly, in this set of biologically poor prognosis tumors, pCR predicts for better outcome, especially when analyzed within breast cancer subsets. Keywords: reference x sample reference x sample
2012-01-13 | E-GEOD-22226 | biostudies-arrayexpress
Project description:Background: MicroRNAs (miRNAs) are small, non-coding, RNA molecules which regulate numerous cellular processes. Specific miRNA may be abnormally down-regulated or up-regulated in colorectal cancer and have been found associated with prognosis or response to treatments. However, no study has ever addressed their predictive role in rectal cancer. Therefore, we used microarray technology and RT-PCR to profile miRNA expression patterns in patients (pts) with rectal cancer, with the aim to identify a specific M-bM-^@M-^\signatureM-bM-^@M-^] associated with pathological complete response after neoadjuvant chemo-radiotherapy. Methods: 38 pts with locally advanced rectal cancer (cT3-4/N+) were treated with capecitabine-oxaliplatin and pelvic conformal radiotherapy (45 cGy) followed by surgery (after 6-8 weeks). Pathologic response was scored according to the tumor regression grade (TRG) scale. MiRNA expression profile was analysed by microarray on fresh frozen biopsies obtained before treatment start and confirmed by RT-PCR. The correlation between miRNA expression profile and the TRG coded as TRG1 (pathologic Complete Response-pCR) versus TRG >1 (no pCR) was assessed by statistical analysis methods specifically designed for this study. Findings: 14 miRNAs were selected by arrays analysis as differentially expressed in TRG1 pts and 13 were confirmed by RT-PCR. In particular, 11 miRNAs (miR-1183, miR-483-5p, miR-622, miR-125a-3p, miR-1224-5p, miR-188-5p, miR-1471, miR-671-5p, miR-1909*, miR-630 and miR-765) were significantly up-regulated in TRG1 pts, while 2 miRNAs were under -expressed (miR-1274b and miR-720). miR-622 and miR-630 showed 100% sensitivity and specificity in selecting TRG1 cases and were significantly correlated with EGFR (M-OM-^G2=11M-bM-^@M-"793; p= 0M-bM-^@M-"001) and TS expression (M-OM-^G2=10M-bM-^@M-"589; p= 0M-bM-^@M-"001). Interpretation: A set of 13 miRNAs is strongly associated with pathologic complete response and may represent a specific marker of response to chemo-radiotherapy in locally advanced rectal cancer. Experiments were performed on purified RNA from preoperatory biopsies of 38 patients with histological diagnosis of rectal adenocarcinoma invading through the intestinal wall and/or with pelvic lymph node involvement as evaluated by endorectal ultrasonography (uT3-T4 and/or uN+). Patients were treated with neoadjuvant chemo-radiotherapy (capecitabine + oxaliplatin in combination with 45 Gy of pelvic conformal radiotherapy). Patients have been divided in the following two groups: group A those who had obtained a pathologic complete response M-bM-^@M-^S TRG 1, including the patient without detectable disease who refused surgery, group B any pathologic response other than complete.
2012-04-24 | E-GEOD-29298 | biostudies-arrayexpress