title: Neoadjuvant doxorubicin/cyclophosphamide followed by ixabepilone or paclitaxel in early stage breast cancer and evaluation of βIII-tubulin expression as a predictive marker.
abstract: BACKGROUND
  This randomized phase II trial was designed to compare the rate of pathologic complete response (pCR) induced by neoadjuvant cyclophosphamide plus doxorubicin (AC) followed by ixabepilone or paclitaxel in women with early stage breast cancer (BC). Expression of βIII-tubulin as a predictive marker was also evaluated.
  
  
  METHODS
  Women with untreated, histologically confirmed primary invasive breast adenocarcinoma received four cycles of AC followed by 1:1 randomization to either ixabepilone 40 mg/m2 (3-hour infusion) every 3 weeks for four cycles (n = 148) or weekly paclitaxel 80 mg/m2 (1-hour infusion) for 12 weeks (n = 147). All patients underwent a core needle biopsy of the primary cancer for molecular marker analysis prior to chemotherapy. βIII-Tubulin expression was assessed using immunohistochemistry.
  
  
  RESULTS
  There was no significant difference in the rate of pCR in the ixabepilone treatment arm (24.3%; 90% confidence interval [CI], 18.6-30.8) and the paclitaxel treatment arm (25.2%; 90% CI, 19.4-31.7). βIII-Tubulin-positive patients obtained higher pCR rates compared with βIII-tubulin-negative patients in both treatment arms; however, βIII-tubulin expression was not significantly associated with a differential response to ixabepilone or paclitaxel. The safety profiles of both regimens were generally similar, although neutropenia occurred more frequently in the ixabepilone arm (grade 3/4: 41.3% vs. 8.4%). The most common nonhematologic toxicity was peripheral neuropathy.
  
  
  CONCLUSIONS
  Neoadjuvant treatment of early stage BC with AC followed by ixabepilone every 3 weeks or weekly paclitaxel was well tolerated with no significant difference in efficacy. Higher response rates were observed among βIII-tubulin-positive patients.
authors.affiliation: Department of Medical Oncology, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona, Spain. csaura@vhebron.net
authors.forename: Cristina
authors.initials: C
authors.lastname: Saura
authors.forename: Ling-Ming
authors.initials: LM
authors.lastname: Tseng
authors.forename: Stephen
authors.initials: S
authors.lastname: Chan
authors.forename: Raju T
authors.initials: RT
authors.lastname: Chacko
authors.forename: Mario
authors.initials: M
authors.lastname: Campone
authors.forename: Alexy
authors.initials: A
authors.lastname: Manikhas
authors.forename: Shona M
authors.initials: SM
authors.lastname: Nag
authors.forename: Cynthia G
authors.initials: CG
authors.lastname: Leichman
authors.forename: Lokanatha
authors.initials: L
authors.lastname: Dasappa
authors.forename: Peter A
authors.initials: PA
authors.lastname: Fasching
authors.forename: Fernando
authors.initials: F
authors.lastname: Hurtado de Mendoza
authors.forename: W Fraser
authors.initials: WF
authors.lastname: Symmans
authors.forename: David
authors.initials: D
authors.lastname: Liu
authors.forename: Pralay
authors.initials: P
authors.lastname: Mukhopadhyay
authors.forename: Christine
authors.initials: C
authors.lastname: Horak
authors.forename: Guan
authors.initials: G
authors.lastname: Xing
authors.forename: Lajos
authors.initials: L
authors.lastname: Pusztai
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D054316:Biomarkers, Pharmacological; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage*; D034261:Epothilones / Q000008:administration & dosage; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D014404:Tubulin / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D054316:Biomarkers, Pharmacological; D034261:Epothilones; C498585:TUBB3 protein, human; D014404:Tubulin; D004317:Doxorubicin; D003520:Cyclophosphamide; C430592:ixabepilone; D017239:Paclitaxel
keywords: Biomarker; Early stage breast cancer; Ixabepilone; Neoadjuvant; βIII-Tubulin