title: Gene expression profiles in paraffin-embedded core biopsy tissue predict response to chemotherapy in women with locally advanced breast cancer.
abstract: OBJECTIVE
  We sought to identify gene expression markers that predict the likelihood of chemotherapy response. We also tested whether chemotherapy response is correlated with the 21-gene Recurrence Score assay that quantifies recurrence risk.
  
  
  METHODS
  Patients with locally advanced breast cancer received neoadjuvant paclitaxel and doxorubicin. RNA was extracted from the pretreatment formalin-fixed paraffin-embedded core biopsies. The expression of 384 genes was quantified using reverse transcriptase polymerase chain reaction and correlated with pathologic complete response (pCR). The performance of genes predicting for pCR was tested in patients from an independent neoadjuvant study where gene expression was obtained using DNA microarrays.
  
  
  RESULTS
  Of 89 assessable patients (mean age, 49.9 years; mean tumor size, 6.4 cm), 11 (12%) had a pCR. Eighty-six genes correlated with pCR (unadjusted P < .05); pCR was more likely with higher expression of proliferation-related genes and immune-related genes, and with lower expression of estrogen receptor (ER) -related genes. In 82 independent patients treated with neoadjuvant paclitaxel and doxorubicin, DNA microarray data were available for 79 of the 86 genes. In univariate analysis, 24 genes correlated with pCR with P < .05 (false discovery, four genes) and 32 genes showed correlation with P < .1 (false discovery, eight genes). The Recurrence Score was positively associated with the likelihood of pCR (P = .005), suggesting that the patients who are at greatest recurrence risk are more likely to have chemotherapy benefit.
  
  
  CONCLUSIONS
  Quantitative expression of ER-related genes, proliferation genes, and immune-related genes are strong predictors of pCR in women with locally advanced breast cancer receiving neoadjuvant anthracyclines and paclitaxel.
authors.affiliation: Medical Oncology, Istituto Nazionale Tumori, Via Venezian, 1, 20133 Milano, Italy. gianni@istitutotumori.mi.it
authors.forename: Luca
authors.initials: L
authors.lastname: Gianni
authors.forename: Milvia
authors.initials: M
authors.lastname: Zambetti
authors.forename: Kim
authors.initials: K
authors.lastname: Clark
authors.forename: Joffre
authors.initials: J
authors.lastname: Baker
authors.forename: Maureen
authors.initials: M
authors.lastname: Cronin
authors.forename: Jenny
authors.initials: J
authors.lastname: Wu
authors.forename: Gabriella
authors.initials: G
authors.lastname: Mariani
authors.forename: Jaime
authors.initials: J
authors.lastname: Rodriguez
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Carcangiu
authors.forename: Drew
authors.initials: D
authors.lastname: Watson
authors.forename: Pinuccia
authors.initials: P
authors.lastname: Valagussa
authors.forename: Roman
authors.initials: R
authors.lastname: Rouzier
authors.forename: W Fraser
authors.initials: WF
authors.lastname: Symmans
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Ross
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
authors.forename: Lajos
authors.initials: L
authors.lastname: Pusztai
authors.forename: Steven
authors.initials: S
authors.lastname: Shak
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001707:Biopsy, Needle; D001940:Breast / Q000473:pathology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D017239:Paclitaxel / Q000627:therapeutic use; D011237:Predictive Value of Tests; D012074:Remission Induction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000970:Antineoplastic Agents; D004317:Doxorubicin; D017239:Paclitaxel