Transcriptomics,Genomics

Dataset Information

54

An expression profile that predicts the therapeutic response of the basal-like breast cancer to neoadjuvant chemotherapy


ABSTRACT: A gene expression signature characterizes expression data from breast cancer samples of patients with pathological complete response (pCR) or residual disease (RD) following the neoadjuvant trial. Several gene expression profiles have been reported to predict breast cancer response to neoadjuvant chemotherapy. These studies often consider breast cancer as a homogeneous entity, although higher rates of pathologic complete response (pCR) are known to occur within the basal-like subclass. We postulated that profiles with higher predictive accuracy could be derived from a subset analysis of basal-like tumors in isolation. Using a previously described ‘‘intrinsic’’ signature to differentiate breast tumor subclasses, we identified 50 basal-like tumors from two independent clinical trials associated with gene expression profile data. 24 tumor data sets (included in this GEO submission) were derived from a 119-patient neoadjuvant trial at our institution and an additional 26 tumor data sets were identified from a published data set (Hess et al. J Clin Oncol 24:4236–4244, 2006). The combined 50 basal-like tumors were partitioned to form a 37 sample training set with 13 sequestered for validation. Clinical surveillance occurred for a mean of 26 months. We identified a 23-gene profile which predicted pCR in basal-like breast cancers with 92% predictive accuracy in the sequestered validation data set. Furthermore, distinct cluster of patients with high rates of cancer recurrence was observed based on cluster analysis with the 23-gene signature. Disease-free survival analysis of these three clusters revealed significantly reduced survival in the patients of this high recurrence cluster. We identified a 23- gene signature which predicts response of basal-like breast cancer to neoadjuvant chemotherapy as well as disease-free survival. This signature is independent of tissue collection method and chemotherapeutic regimen. Keywords: Disease state analysis Overall design: Core biopsies were obtained from 86 patients prior to neoadjuvant therapy out of which 70 fulfilled the requirements to undergo expression analysis (24 of these 70 were used in the published analysis). pCR was defined as no residual invasive disease in the breast or lymph nodes. Residual in situ carcinoma was also considered as pCR. RNA was extracted from snap frozen 14-gauge core samples obtained from pre-treatment tumors. Specimens containing more than 40% of tumor on histological examination were analyzed.

INSTRUMENT(S): [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array

SUBMITTER: Rekha Meyer  

PROVIDER: GSE19697 | GEO | 2009-12-30

SECONDARY ACCESSION(S): PRJNA121873

REPOSITORIES: GEO

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Publications

A gene expression signature that predicts the therapeutic response of the basal-like breast cancer to neoadjuvant chemotherapy.

Lin Yiing Y   Lin Shin S   Watson Mark M   Trinkaus Kathryn M KM   Kuo Sacha S   Naughton Michael J MJ   Weilbaecher Katherine K   Fleming Timothy P TP   Aft Rebecca L RL  

Breast cancer research and treatment 20091206 3


Several gene expression profiles have been reported to predict breast cancer response to neoadjuvant chemotherapy. These studies often consider breast cancer as a homogeneous entity, although higher rates of pathologic complete response (pCR) are known to occur within the basal-like subclass. We postulated that profiles with higher predictive accuracy could be derived from a subset analysis of basal-like tumors in isolation. Using a previously described "intrinsic" signature to differentiate bre  ...[more]

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