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HER-2/neu Overexpression As a Poor Prognostic Factor for Patients with Metastatic Breast Cancer undergoing High-dose Chemotherapy with Autologous Stem Cell Transplantation

Departments of Pathology [Y. S. K., A. A. S.], Blood and Marrow Transplantation [S. N. K., F. M., G. R., R. E. C., N. T. U.], Biostatistics [E. H., T. L. S.], and Molecular and Cellular Oncology [N. T. U.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

Purpose: High-dose chemotherapy with autologous stem cell transplantation (HDCT) produces a high tumor response rate for patients with metastatic breast cancer and have 20% long-term progression-free survival. Overexpression of HER-2/neu oncoprotein predicts outcome in patients with breast cancer given standard-dose chemotherapy. Therefore, we evaluated whether the HER-2/neu overexpression in the primary tumor predicts clinical outcome in patients with metastatic breast cancer given HDCT.

Experimental Design: A total of 236 patients were given standard-dose induction chemotherapy followed by stem cell collection; high-dose chemotherapy with cyclophosphamide, thiotepa, and carmustine; and stem cell infusion. HER-2/neu expression was assessed by immunostaining with anti-HER-2/neu e2–4001 monoclonal antibody in 63 patients.

Results: Clinical characteristics and survival were similar for patients with known and unknown HER-2/neu status. HER-2/neu was overexpressed in 22 of 63 tumors (35%). There was some tendency for HER-2/neu overexpression to be associated with the absence of estrogen or progesterone receptors. In considering the association of HER-2/neu expression with patient outcomes, HER-2/neu overexpression was associated with generally shorter overall survival (P = 0.02) and progression-free survival (P < 0.01), and this association persisted to a lesser extent after adjustment for differences in important prognostic factors between the two groups.

Conclusion: We conclude that HER-2/neu overexpression may represent an additional prognostic factor for patients with metastatic breast cancer who undergo HDCT.

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