title: A gene expression signature that predicts the therapeutic response of the basal-like breast cancer to neoadjuvant chemotherapy.
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.
authors.affiliation: Department of Surgery, Washington University School of Medicine St. Louis, 660 South Euclid Avenue, Campus Box 8109, St. Louis, MO 63110, USA.
authors.forename: Yiing
authors.initials: Y
authors.lastname: Lin
authors.forename: Shin
authors.initials: S
authors.lastname: Lin
authors.forename: Mark
authors.initials: M
authors.lastname: Watson
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Trinkaus
authors.forename: Sacha
authors.initials: S
authors.lastname: Kuo
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Naughton
authors.forename: Katherine
authors.initials: K
authors.lastname: Weilbaecher
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Fleming
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Aft
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D002986:Clinical Trials as Topic; D016000:Cluster Analysis; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D005820:Genetic Testing; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D018295:Neoplasms, Basal Cell / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D013997:Time Factors; D016896:Treatment Outcome