title: PTEN Loss Is Associated with Worse Outcome in HER2-Amplified Breast Cancer Patients but Is Not Associated with Trastuzumab Resistance.
abstract: OBJECTIVE
  To investigate the clinical relevance of PTEN in HER2-amplified and HER2-nonamplified disease.
  
  
  METHODS
  We assessed PTEN status in two large adjuvant breast cancer trials (BCIRG-006 and BCIRG-005) using a PTEN immunohistochemical (IHC) assay that was previously validated in a panel of 33 breast cancer cell lines and prostate cancer tissues with known PTEN gene deletion.
  
  
  RESULTS
  In the HER2-positive patient population, absence of tumor cell PTEN staining occurred at a rate of 5.4% and was independent of ER/PR status. In contrast, 15.9% of HER2-negative patients exhibited absence of PTEN staining with the highest frequency seen in triple-negative breast cancer (TNBC) subgroup versus ER/PR-positive patients (35.1% vs. 10.9%). Complete absence of PTEN staining in tumor cells was associated with poor clinical outcome in HER2-positive disease. Those patients whose cancers demonstrated absent PTEN staining had a significant decrease in disease-free survival (DFS) and overall survival (OS) compared with patients with tumors exhibiting any PTEN staining patterns (low, moderate, or high). Trastuzumab appeared to provide clinical benefit even for patients lacking PTEN staining. In the HER2-negative population, there were no statistically significant differences in clinical outcome based on PTEN status.
  
  
  CONCLUSIONS
  This study is the largest to date examining PTEN status in breast cancer and the data suggest that the rate and significance of PTEN status differ between HER2-positive and HER2-negative disease. Furthermore, the data clearly suggest that HER2-positive patients with PTEN loss still benefit from trastuzumab.
authors: Genentech Research and Early Development, South San Francisco, California.
authors: Howard M
authors: HM
authors: Stern
authors: AstraZeneca, Waltham, Massachusetts.
authors: Humphrey
authors: H
authors: Gardner
authors: International Drug Development Institute, Louvain-la-Neuve, Belgium.
authors: Tomasz
authors: T
authors: Burzykowski
authors: USC/Norris Comprehensive Cancer Center, Los Angeles, California.
authors: Wafaa
authors: W
authors: Elatre
authors: Genentech Research and Early Development, South San Francisco, California.
authors: Carol
authors: C
authors: O'Brien
authors: Genentech Research and Early Development, South San Francisco, California.
authors: Mark R
authors: MR
authors: Lackner
authors: Ventana Medical Systems, Inc., Tucson, Arizona.
authors: Gary A
authors: GA
authors: Pestano
authors: USC/Norris Comprehensive Cancer Center, Los Angeles, California.
authors: Angela
authors: A
authors: Santiago
authors: USC/Norris Comprehensive Cancer Center, Los Angeles, California.
authors: Ivonne
authors: I
authors: Villalobos
authors: Frauenklinik vom Roten Kreuz, Munich, Germany.
authors: Wolfgang
authors: W
authors: Eiermann
authors: Maria Sklodowska-Curie (MSC) Centre, Warsaw, Poland.
authors: Tadeusz
authors: T
authors: Pienkowski
authors: Hospital Universitario San Carlos, Madrid, Spain.
authors: Miguel
authors: M
authors: Martin
authors: Virginia Cancer Specialists/U.S. Oncology Research Network, Fairfax, Virginia.
authors: Nicholas
authors: N
authors: Robert
authors: Irish Cooperative Oncology Research Group, St. Vincent's University Hospital, Dublin, Ireland.
authors: John
authors: J
authors: Crown
authors: Vall d'Hebron Institute of Oncology, Barcelona, Spain.
authors: Paolo
authors: P
authors: Nuciforo
authors: Cancer International Research Group/Translational Research in Oncology, Paris, France.
authors: Valerie
authors: V
authors: Bee
authors: Department of Oncology, University of Alberta, Edmonton, Canada.
authors: John
authors: J
authors: Mackey
authors: Department of Medicine, Geffen School of Medicine at UCLA, Los Angeles, California. press@usc.edu DSlamon@mednet.ucla.edu.
authors: Dennis J
authors: DJ
authors: Slamon
authors: USC/Norris Comprehensive Cancer Center, Los Angeles, California. press@usc.edu DSlamon@mednet.ucla.edu.
authors: Michael F
authors: MF
authors: Press
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D046888:Tissue Array Analysis; D000068878:Trastuzumab / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D051059:PTEN Phosphohydrolase; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human; C494929:PTEN protein, human
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