Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Serial gene expression analysis in locally advanced breast cancer patients who failed to respond to neoadjuvant chemotherapy

ABSTRACT: 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

ORGANISM(S): Homo sapiens

SUBMITTER: Mark Magbanua

PROVIDER: E-GEOD-32603 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Serial expression analysis of breast tumors during neoadjuvant chemotherapy reveals changes in cell cycle and immune pathways associated with recurrence and response.

Magbanua Mark Jesus M MJ Wolf Denise M DM Yau Christina C Davis Sarah E SE Crothers Julia J Au Alfred A Haqq Christopher M CM Livasy Chad C Rugo Hope S HS Esserman Laura L Park John W JW van 't Veer Laura J LJ

Breast cancer research : BCR 20150529

<h4>Introduction</h4>The molecular biology involving neoadjuvant chemotherapy (NAC) response is poorly understood. To elucidate the impact of NAC on the breast cancer transcriptome and its association with clinical outcome, we analyzed gene expression data derived from serial tumor samples of patients with breast cancer who received NAC in the I-SPY 1 TRIAL.<h4>Methods</h4>Expression data were collected before treatment (T1), 24-96 hours after initiation of chemotherapy (T2) and at surgery (TS). ...[more]

PMID: 26021444

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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

Dataset Information

Serial gene expression analysis in locally advanced breast cancer patients who failed to respond to neoadjuvant chemotherapy

Publications

Serial expression analysis of breast tumors during neoadjuvant chemotherapy reveals changes in cell cycle and immune pathways associated with recurrence and response.

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