Activation (tyrosine phosphorylation) of ErbB-2 (HER-2/neu): A study of incidence and correlation with outcome in breast cancer

Purpose: We hypothesize that phosphorylated ErbB-2 (P-ErbB-2, identified by a novel antibody PN2A) may provide either more significant or additional p rognostic marker data for breast cancer patients. This study was designed t o compare the incidence and prognostic value of ErbB-2 (HER-2/neu) and P-Er bB-2 immunoexpression in archival breast cancer samples. Materials and Methods: Eight hundred sixteen invasive breast cancers with a median of 16.3 years of follow-up were immunostained for ErbB-2 (using ant ibody CB11) and P-ErbB-2 (using antibody PN2A). ErbB-2 and P-ErbB-2 data we re compared with clinical, histologic, immunohistochemical, and outcome var iables. Results: Of 816 primary breast cancers, 307 (38%) were positive for ErbB-2 and 37(12% of ErbB-2 positive and 5% of the study population) expressed P-E rbB-2, P-ErbB-2 was not detected in ErbB-2-negative cases (n = 509). ErbB-2 immunohistochemical data were bimodal; patients with greater than or equal to 80% cellular expression had the shortest disease-free and disease-speci fic survival. P-ErbB-2 was associated with a higher percentage of ErbB-2-po sitive cells, a higher number of positive lymph nodes, and cellular prolife ration. ErbB-2 and P-ErbB-2 were indicators of poor prognosis in node-posit ive patients in bath univariate and multivariate analyses. We found that ei ther P-ErbB-2 expression or high (greater than or equal to 80%) ErbB-2 expr ession provided the most significant prognostic value in node-positive case s by multivariate analyses. There were too few P-ErbB-2-positive cases and events in the node-negative patient group to allow statistical analysis of p-ErbB-2 in that subgroup. Conclusion: PN2A immunostaining identified a subset (approximately 12% of E rbB-2-positive breast cancers) with activation (phosphorylation) of the rec eptor ErbB-2. P-ErbB-2 expression was strongly associated with higher level s of ErbB-2 expression (greater than or equal to 80%), although it was not a surrogate. Identification of cases with a high percentage of invasive bre ast cancer cells expressing ErbB-2 or determination of receptor activation via P-ErbB-2 may provide additional prognostic value in node-positive breas t cancers. (C) 2000 by American Society of Clinical Oncology.