Phosphorylated/activated HER2 as a marker of clinical resistance to single agent taxane chemotherapy for metastatic breast cancer Journal Article


Authors: Modi, S.; DiGiovanna, M. P.; Lu, Z.; Moskowitz, C.; Panageas, K. S.; Van Poznak, C.; Hudis, C. A.; Norton, L.; Tan, L.; Stern, D. F.; Carter, D.; Seidman, A. D.
Article Title: Phosphorylated/activated HER2 as a marker of clinical resistance to single agent taxane chemotherapy for metastatic breast cancer
Abstract: Purpose. To determine the association of phosphorylated/ activated HER2 (P-HER2) and response to taxane chemotherapy in patients with metastatic breast cancer (MBC). Materials and Methods. Archived tumor specimens of patients with MBC treated on clinical trials with taxane monotherapy were analyzed by immunohistochemistry (IHC) for the presence of phosphorylated HER2 using the PN2A monoclonal antibody. Chi-squared analysis was performed to evaluate the association of P-HER2 status and efficacy of single agent taxane therapy. Results. One hundred twenty-six cases were identified as evaluable for both IHC and clinical outcome. Twelve cases (10 percent) were positive for P-HER2, of which 5 had evidence of clinical progression and 7 had evidence of clinical benefit with taxane therapy. Of the 114 cases that were negative for P-HER2, 20 demonstrated progression and 94 had clinical benefit. Chi-squared analysis revealed a significant correlation between the presence of P-HER2 and resistance to taxane therapy, χ2 = 3.9724 and p = 0.046. Conclusions. Phosphorylated/activated HER2 is associated with clinical resistance to single agent taxane therapy for MBC. The likelihood of direct progression of disease on taxane was greater in cases of PN2A-positive tumors (42 percent) as opposed to PN2A-negative ones (18 percent, p = 0.046). Functional assessment of HER2 status may provide unique predictive information not seen with conventional assessments. Copyright © Taylor & Francis Inc.
Keywords: immunohistochemistry; signal transduction; cancer chemotherapy; human tissue; protein phosphorylation; treatment outcome; retrospective studies; major clinical study; drug efficacy; monotherapy; antineoplastic agents; paclitaxel; metastasis; breast cancer; epidermal growth factor receptor 2; tumor markers, biological; drug resistance, neoplasm; breast neoplasms; phosphorylation; cancer resistance; docetaxel; antibodies, monoclonal; neoplasm metastasis; receptor, erbb-2; taxoids; taxane derivative; her2; taxanes; bridged compounds
Journal Title: Cancer Investigation
Volume: 23
Issue: 6
ISSN: 0735-7907
Publisher: Informa Healthcare  
Date Published: 2005-01-01
Start Page: 483
End Page: 487
Language: English
DOI: 10.1080/07357900500201301
PUBMED: 16203655
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 26" - "Export Date: 24 October 2012" - "CODEN: CINVD" - "Source: Scopus"
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MSK Authors
  1. Andrew D Seidman
    318 Seidman
  2. Clifford Hudis
    905 Hudis
  3. Larry Norton
    758 Norton
  4. Lee K Tan
    147 Tan
  5. Chaya S. Moskowitz
    280 Moskowitz
  6. Shanu Modi
    267 Modi
  7. Katherine S Panageas
    512 Panageas