title: PTEN expression as a predictor for the response to trastuzumab-based therapy in Her-2 overexpressing metastatic breast cancer.
abstract: BACKGROUND
  Even though trastuzumab is an effective therapy in early stage Her-2+ breast cancer, 40-50% of advanced Her-2+ breast cancer patients develop trastuzumab resistance. A potential resistance mechanism is aberrant downstream signal transmission due to loss of phosphatase and tensin homologue (PTEN). This study investigated the relationship between the expression of PTEN and trastuzumab response in Her-2 overexpressing metastatic breast cancer patients.
  
  
  METHODS
  Between 2000 and 2007, 164 patients with Her-2+ metastatic breast cancer received trastuzumab-based therapy in our institution. We analyzed PTEN status by immunohistochemistry of 115 available tumor tissues and analyzed associations with other histopathological parameters, response rate, progression free survival (PFS) and overall survival (OS) with a median follow-up of 60 months.
  
  
  RESULTS
  Eighty patients were PTEN positive (69.6%) and 35 patients PTEN negative (30.4%). We found a significant association of the expression of PTEN and p53 (p = 0.041), while there was no association with grading, hormone receptor status, IGFR or MIB. We found significantly more cases with progressive disease under trastuzumab-based therapy in patients with PTEN positive breast cancers (p = 0.018), while there was no significant correlation with PFS or OS.
  
  
  CONCLUSIONS
  In Her-2-positive metastatic breast cancers, PTEN positivity was significantly associated with progressive disease, but not with PFS or OS.
authors.affiliation: Department of Obstetrics and Gynecology, Cancer Comprehensive Center, Medical University of Vienna, Vienna, Austria.
authors.forename: Daphne
authors.identifier: http://orcid.org/0000-0002-7401-0987
authors.initials: D
authors.lastname: Gschwantler-Kaulich
authors.affiliation: Department of Obstetrics and Gynecology, Cancer Comprehensive Center, Medical University of Vienna, Vienna, Austria.|QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
authors.forename: Yen Y
authors.initials: YY
authors.lastname: Tan
authors.affiliation: Clinical Division of Oncology, Department of Medicine I and Center for Excellence in Clinical and Experimental Oncology, Medical University of Vienna, Vienna, Austria.
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Fuchs
authors.affiliation: Department of Obstetrics and Gynecology, Cancer Comprehensive Center, Medical University of Vienna, Vienna, Austria.|Department of Obstetrics and Gynaecology, Wilhelminenspital, Vienna, Austria.
authors.forename: Gernot
authors.initials: G
authors.lastname: Hudelist
authors.affiliation: Clinical Division of Oncology, Department of Medicine I and Center for Excellence in Clinical and Experimental Oncology, Medical University of Vienna, Vienna, Austria.
authors.forename: Wolfgang J
authors.initials: WJ
authors.lastname: Köstler
authors.affiliation: Department of Pathology, Sozialmedizinisches Zentrum Ost, Vienna, Austria.
authors.forename: Angelika
authors.initials: A
authors.lastname: Reiner
authors.affiliation: Department of Obstetrics and Gynecology, Cancer Comprehensive Center, Medical University of Vienna, Vienna, Austria.
authors.forename: Carmen
authors.initials: C
authors.lastname: Leser
authors.affiliation: Department of Thoracic Surgery, Otto Wagner Hospital, Vienna, Austria.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Salama
authors.affiliation: Department of Pathology, Otto Wagner Hospital, Vienna, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Attems
authors.affiliation: Department of Obstetrics and Gynecology, Cancer Comprehensive Center, Medical University of Vienna, Vienna, Austria.
authors.forename: Christine
authors.initials: C
authors.lastname: Deutschmann
authors.affiliation: Clinical Division of Oncology, Department of Medicine I and Center for Excellence in Clinical and Experimental Oncology, Medical University of Vienna, Vienna, Austria.
authors.forename: Christoph C
authors.initials: CC
authors.lastname: Zielinski
authors.affiliation: Department of Obstetrics and Gynecology, Cancer Comprehensive Center, Medical University of Vienna, Vienna, Austria.
authors.forename: Christian F
authors.initials: CF
authors.lastname: Singer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D000068878:Trastuzumab / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D051059:PTEN Phosphohydrolase; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C494929:PTEN protein, human