Measurement of Intracellular and Extracellular Domain-Specific HER2 Expression May Predict Increased Benefit of Adjuvant Trastuzumab in Breast Cancer
In a study reported in the Journal of the National Cancer Institute, Carvajal-Hausdorf et al found that quantitative measurement of HER2 protein expression in intracellular and extracellular domains indicated improved disease-free survival with adjuvant trastuzumab (Herceptin) in breast cancer patients with high vs low extracellular domain expression.
Study Details
In the study, HER2 protein expression was measured with quantitative immunofluorescence in tissue microarrays using different antibodies to target the intracellular domain (CB11 and A0485) and extracellular domain (SP3 and D8F12). The prognostic value of intracellular and extracellular domain expression was assessed in 180 patients from a clinical trial of adjuvant chemotherapy followed by trastuzumab (HeCOG 10/05).
Association With Disease-Free Survival
HER2 intracellular domain expression on quantitative immunofluorescence had higher sensitivity vs extracellular domain expression in predicting ERBB2 (HER2) gene amplification, whereas extracellular domain expression had greater specificity and higher positive predictive value. In the clinical trial samples, 15% of cases were discordant for intracellular and extracellular domain expression.
High extracellular domain expression was associated with significantly longer disease-free survival (hazard ratio [HR] = 0.31, P = .049), whereas no significant difference was observed for high vs low intracellular domain expression. Among patients with low extracellular domain expression, no difference in disease-free survival was found for high vs low intracellular domain expression. Among patients with high intracellular domain expression, disease-free survival was significantly prolonged for those with high vs low extracellular domain (HR = 0.23, P = .027).
The investigators concluded: “Quantitative measurements of HER2 [intracellular and extracellular domain] expression in breast cancer suggest a subclassification of HER2-positive tumors. Trastuzumab-treated patients with high [extracellular domain] showed better [disease-free survival] than patients with low [extracellular domain]. This suggests differential benefit from trastuzumab therapy based on HER2 [extracellular domain] expression.”
David L. Rimm, MD, PhD, of Yale University School of Medicine, is the corresponding author for the Journal of the National Cancer Institute article.
The study was supported by the Breast Cancer Research Foundation. For full disclosures of the study authors, visit jnci.oxfordjournals.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
