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, chi2 = 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.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
authors.forename: Shanu
authors.initials: S
authors.lastname: Modi
authors.forename: Michael P
authors.initials: MP
authors.lastname: DiGiovanna
authors.forename: Zhao
authors.initials: Z
authors.lastname: Lu
authors.forename: Chaya
authors.initials: C
authors.lastname: Moskowitz
authors.forename: Katherine S
authors.initials: KS
authors.lastname: Panageas
authors.forename: Catherine
authors.initials: C
authors.lastname: Van Poznak
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Hudis
authors.forename: Larry
authors.initials: L
authors.lastname: Norton
authors.forename: Lee
authors.initials: L
authors.lastname: Tan
authors.forename: David F
authors.initials: DF
authors.lastname: Stern
authors.forename: Darryl
authors.initials: D
authors.lastname: Carter
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Seidman
mesh_terms: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000188:drug therapy*; D001952:Bridged-Ring Compounds / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009362:Neoplasm Metastasis; D010766:Phosphorylation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D012189:Retrospective Studies; D043823:Taxoids / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D001952:Bridged-Ring Compounds; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; C080625:taxane