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Stem Cell Dose and Tumorbiologic Parameters as Prognostic Markers for Patients with Metastatic Breast Cancer Undergoing High-Dose Chemotherapy with Autologous Blood Stem Cell Support

^a Department of Internal Medicine V;
^b Department of Gynecology and Obstetrics;
^c Department of Pathology, University of Heidelberg, Heidelberg, Germany;
^d Department of Hematology and Oncology, University of Düsseldorf, Düsseldorf, Germany

Key Words. Metastatic breast cancer • High-dose chemotherapy • Prognostic factors • CD34⁺ cell dose • Blood stem cell transplantation

Anthony D. Ho, M.D., Department of Medicine V, Hospitalstrasse 3, D-69115 Heidelberg, Germany. Telephone: 49-6221-568001; Fax: 49-6221-565813; e-mail: Anthony_Ho{at}med.uni-heidelberg.de; www.poliklinik-hd.de

We report on the prognostic significance of tumorbiologic parameters and CD34⁺ cell dose in 120 patients with metastatic breast cancer (MBC) who received high-dose chemotherapy (HDCT) with autologous blood stem cell transplantation as first-line treatment. Her2/neu, p53, Ki67, and bcl-2 protein expression were studied using immunohistochemical staining on formalin-fixed, paraffin-embedded primary tumor sections. DNA content of tumor cells (DNA-index) and tumor cell proliferation (S-phase fraction) were measured by DNA flow cytometry. The relationship between these parameters and the CD34⁺ cell dose and progression free (PFS) and overall survival (OS) was analyzed.

With a median follow-up period of 40 months (range, 7-89 months), no more than two metastatic sites (relative risk [RR] = 3.84 [95% confidence interval (CI) 1.49-10]; p =.005) and hyperploidy (RR = 2.58 [95% CI 1.26-5.26]; p = .009) were independent predictors of longer PFS according to multivariate analysis. Independent prognostic factors of longer OS included one or two metastatic sites (RR = 4.16 [95% CI 1.96-4.16]; p < .001), a positive combined hormone receptor status (RR = 2.45 [95% CI 1.45-4.14]; p = .001) and a high number of infused stem cells (>7.8 x 10⁶ CD34⁺ cells per kg body weight) (RR = 2.0 [95% CI 1.17-3.42]; p = .01).

In conclusion, positive hormone receptors, 2 metastatic sites, high DNA-index and high CD34⁺ cell dose (>7.8 x 10⁶ CD34⁺ cells per kg) are predictors for a favorable outcome after autotransplantation for MBC. Our observation might indicate a favorable effect of HDCT in MBC patients with overexpression of Her2/neu who might have a worse prognosis when treated with conventional chemotherapy.

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