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

Yiing Lin, Shin Lin, Mark Watson, Kathryn M. Trinkaus, Sacha Kuo, Michael J. Naughton, Katherine Weilbaecher, Timothy P. Fleming, Rebecca L. Aft

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

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 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.

Original languageEnglish
Pages (from-to)691-699
Number of pages9
JournalBreast Cancer Research and Treatment
Volume123
Issue number3
DOIs
StatePublished - Oct 2010

Keywords

  • Breast cancer
  • Expression profiling
  • Therapeutic response

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