title: An open-label study of lapatinib in women with HER-2-negative early breast cancer: the lapatinib pre-surgical study (LPS study).
abstract: BACKGROUND
  This phase II, open-label, multicentre study aimed to evaluate changes in cell proliferation and biomarkers, as well as efficacy of lapatinib in treatment-naïve patients with HER-2-negative primary breast cancer.
  
  
  METHODS
  Patients received 1500 mg lapatinib for 28-42 days before surgery with repeat biopsies and measurements. The primary end point was inhibition of cell proliferation measured by Ki67; the secondary end points included clinical response, adverse events and changes in FOXO3a, FOXM1, p-AKT and HER-3.
  
  
  RESULTS
  Overall, there was no significant reduction in Ki67 with treatment (assessment carried out in 28 of 31 subjects enrolled). However, four patients (14%) showed a reduction in Ki67 ≥50%. Four of 25 patients (16%) had a partial response to treatment judged by sequential ultrasound measurements. Response, in terms of either Ki67 or ultrasound, did not relate to changes in any biomarker assessed at baseline, including the estrogen receptor (ER) and epidermal growth factor receptor (EGFR). However, all four clinical responders were HER-3 positive, as were three of four Ki67 responders.
  
  
  CONCLUSIONS
  Overall, a pre-surgical course of lapatinib monotherapy had little effect on this group of patients; however, in subsets of patients, especially those with HER-3-positive tumors, we observed either reduction in proliferation (Ki67) or tumor size; EGFR/ER status had no impact.
authors.affiliation: Division of Cancer, Department of Surgery and Cancer, Imperial College London, 1st Floor ICTEM, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK.
authors.forename: R C
authors.initials: RC
authors.lastname: Coombes
authors.forename: T
authors.initials: T
authors.lastname: Tat
authors.forename: M L
authors.initials: ML
authors.lastname: Miller
authors.forename: J A
authors.initials: JA
authors.lastname: Reise
authors.forename: J L
authors.initials: JL
authors.lastname: Mansi
authors.forename: D J
authors.initials: DJ
authors.lastname: Hadjiminas
authors.forename: S
authors.initials: S
authors.lastname: Shousha
authors.forename: S E
authors.initials: SE
authors.lastname: Elsheikh
authors.forename: E W-F
authors.initials: EW
authors.lastname: Lam
authors.forename: Y
authors.initials: Y
authors.lastname: Horimoto
authors.forename: M
authors.initials: M
authors.lastname: El-Bahrawy
authors.forename: E O
authors.initials: EO
authors.lastname: Aboagye
authors.forename: K B
authors.initials: KB
authors.lastname: Contractor
authors.forename: J A
authors.initials: JA
authors.lastname: Shaw
authors.forename: R A
authors.initials: RA
authors.lastname: Walker
authors.forename: M H
authors.initials: MH
authors.lastname: Marconell
authors.forename: C
authors.initials: C
authors.lastname: Palmieri
authors.forename: J
authors.initials: J
authors.lastname: Stebbing
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D000072278:Forkhead Box Protein M1; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D000077341:Lapatinib; D008875:Middle Aged; D051058:Oncogene Protein v-akt / Q000378:metabolism; D011799:Quinazolines / Q000008:administration & dosage*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D020893:Receptor, ErbB-3 / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism
chemical_list: D066246:ErbB Receptors; D000072278:Forkhead Box Protein M1; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D019394:Ki-67 Antigen; D000077341:Lapatinib; D051058:Oncogene Protein v-akt; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D011960:Receptors, Estrogen; C107585:FOXM1 protein, human; C499517:FOXO3 protein, human; C508053:ERBB2 protein, human