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

Shanu Modi, Michael P. DiGiovanna, Zhao Lu, Chaya Moskowitz, Katherine S. Panageas, Catherine Van Poznak, Clifford A. Hudis, Larry Norton, Lee Tan, David F. Stern, Darryl Carter, Andrew D. Seidman

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)483-487
Number of pages5
JournalCancer Investigation
Volume23
Issue number6
DOIs
StatePublished - 2005
Externally publishedYes

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Biomarkers
Breast Neoplasms
Drug Therapy
Immunohistochemistry
Therapeutics
taxane
Disease Progression
Neoplasms
Monoclonal Antibodies
Clinical Trials

Keywords

  • HER2
  • Immunohistochemistry
  • Phosphorylation
  • Taxanes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Modi, S., DiGiovanna, M. P., Lu, Z., Moskowitz, C., Panageas, K. S., Van Poznak, C., ... Seidman, A. D. (2005). Phosphorylated/activated HER2 as a marker of clinical resistance to single agent taxane chemotherapy for metastatic breast cancer. Cancer Investigation, 23(6), 483-487. https://doi.org/10.1080/07357900500201301

Phosphorylated/activated HER2 as a marker of clinical resistance to single agent taxane chemotherapy for metastatic breast cancer. / Modi, Shanu; DiGiovanna, Michael P.; Lu, Zhao; Moskowitz, Chaya; Panageas, Katherine S.; Van Poznak, Catherine; Hudis, Clifford A.; Norton, Larry; Tan, Lee; Stern, David F.; Carter, Darryl; Seidman, Andrew D.

In: Cancer Investigation, Vol. 23, No. 6, 2005, p. 483-487.

Research output: Contribution to journalArticle

Modi, S, DiGiovanna, MP, Lu, Z, Moskowitz, C, Panageas, KS, Van Poznak, C, Hudis, CA, Norton, L, Tan, L, Stern, DF, Carter, D & Seidman, AD 2005, 'Phosphorylated/activated HER2 as a marker of clinical resistance to single agent taxane chemotherapy for metastatic breast cancer', Cancer Investigation, vol. 23, no. 6, pp. 483-487. https://doi.org/10.1080/07357900500201301
Modi, Shanu ; DiGiovanna, Michael P. ; Lu, Zhao ; Moskowitz, Chaya ; Panageas, Katherine S. ; Van Poznak, Catherine ; Hudis, Clifford A. ; Norton, Larry ; Tan, Lee ; Stern, David F. ; Carter, Darryl ; Seidman, Andrew D. / Phosphorylated/activated HER2 as a marker of clinical resistance to single agent taxane chemotherapy for metastatic breast cancer. In: Cancer Investigation. 2005 ; Vol. 23, No. 6. pp. 483-487.
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AU - Modi, Shanu

AU - DiGiovanna, Michael P.

AU - Lu, Zhao

AU - Moskowitz, Chaya

AU - Panageas, Katherine S.

AU - Van Poznak, Catherine

AU - Hudis, Clifford A.

AU - Norton, Larry

AU - Tan, Lee

AU - Stern, David F.

AU - Carter, Darryl

AU - Seidman, Andrew D.

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N2 - 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.

AB - 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.

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