HER-2/neu expression and prognosis in breast cancer
Dept. of Interdisciplinary Oncology, University of South Florida, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, United States
Introduction/Aim: The HER-2/neu oncogene, related to EGFR, is overexpressed/amplified in a significant minority of human invasive breast cancers. Gene amplification and/or protein expression has been evaluated in normal breast epithelium, hyperplasia and in in-situ and invasive breast cancers. Its prognostic value in the latter has been extensively studied. A variety of testing modalities for HER-2/neu are currently used. Materials and Methods/Results: A review of published articles have reported these significant findings: 1) Normal breast epithelium/duct hyperplasia: No amplification 2) Atypical ductal hyperplasia/low grade DCIS: Variable expression; less significantly less than high grade DCIS 3) High grade DCIS: Expressed more often than in invasive tumors. Less often expressed with ER+, PR+ tumors. Recent report of protein overexpression associated with a greater risk of breast cancer recurrence. 4) LCIS/invasive lobular carcinoma: Few data, but over-expression is rare in ILC. 5) Invasive cancer (“early” stages): About 20 % over-expressed. Generally associated with impaired survival, especially in node positive disease. 6) Metastatic cancer: About 30% over-expressed. Associated with relative resistance to tamoxifen, shorter survival, and high incidence of brain metastases. 7) Patient with strongly over-expressing HER-2/neu invasive breast cancer more likely to respond to antracycline-based chemotherapy and to trastuzumab in metastatic setting. The adjuvant use of trastuzumab in high-risk breast cancer patients is presently under study in clinical trials. Conclusion: HER-2/neu over-expression is of clinical value in assessing prognosis and choice of treatment for invasive breast cancers, particularly with the availability of trastuzumab. The clinical relevance of over-expression in ADH and DCIS remains to be clarified.
Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in plenary session 801 (Predictive markers & validation).