title: 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.affiliation: Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Hensel
authors.forename: Andreas
authors.initials: A
authors.lastname: Schneeweiss
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Sinn
authors.forename: Gerlinde
authors.initials: G
authors.lastname: Egerer
authors.forename: Martin
authors.initials: M
authors.lastname: Kornacker
authors.forename: Erich
authors.initials: E
authors.lastname: Solomayer
authors.forename: Rainer
authors.initials: R
authors.lastname: Haas
authors.forename: Gunther
authors.initials: G
authors.lastname: Bastert
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Ho
mesh_terms: D000328:Adult; D000367:Age Factors; D018952:Antigens, CD34 / Q000096:biosynthesis; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001781:Blood Component Removal; D001943:Breast Neoplasms / Q000175:diagnosis / Q000473:pathology* / Q000628:therapy*; D004247:DNA / Q000096:biosynthesis; D005260:Female; D005434:Flow Cytometry; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D013234:Stem Cells / Q000166:cytology*; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
chemical_list: D018952:Antigens, CD34; D000970:Antineoplastic Agents; D004247:DNA; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53