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.

Abstract

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 10(6) CD34(+) cells per kg body weight) (RR = 2.0 [95% CI 1.17-3.42]; p =.01). In conclusion, positive hormone receptors, < or =2 metastatic sites, high DNA-index and high CD34(+) cell dose (>7.8 x 10(6) 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.

• Authors: Manfred Hensel, Andreas Schneeweiss, Hans-Peter Sinn, Gerlinde Egerer, Martin Kornacker, Erich Solomayer, Rainer Haas, Gunther Bastert, Anthony D Ho
• Journal: Stem cells (Dayton, Ohio) (Stem Cells) Vol. 20 Issue 1 Pg. 32-40 ( 2002) ISSN: 1066-5099 [Print] England
• PMID: 11796920 (Publication Type: Journal Article)

Chemical References

• Antigens, CD34
• Antineoplastic Agents
• Ki-67 Antigen
• Proto-Oncogene Proteins c-bcl-2
• Tumor Suppressor Protein p53
• DNA
• Receptor, ErbB-2

Topics

• Adult
• Age Factors
• Antigens, CD34 (biosynthesis)
• Antineoplastic Agents (therapeutic use)
• Blood Component Removal
• Breast Neoplasms (diagnosis, pathology, therapy)
• DNA (biosynthesis)
• Female
• Flow Cytometry
• Hematopoietic Stem Cell Transplantation
• Humans
• Immunohistochemistry
• Ki-67 Antigen (biosynthesis)
• Middle Aged
• Multivariate Analysis
• Neoplasm Metastasis
• Prognosis
• Proto-Oncogene Proteins c-bcl-2 (biosynthesis)
• Receptor, ErbB-2 (biosynthesis)
• Stem Cells (cytology)
• Time Factors
• Tumor Suppressor Protein p53 (biosynthesis)