Soluble Fas (CD95) is a prognostic factor in patients with metastatic breast cancer undergoing high-dose chemotherapy and autologous stem cell transplantation

M. Bewick, M. Conlon, A. M. Parissenti, H. Lee, L. Zhang, S. Glück, R. M. Lafrenie

Research output: Contribution to journalArticle

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Abstract

The Fas/Fas ligand (FasL) system plays an important role in cellular apoptosis and is involved in cancer cell death induced by the immune system and anticancer drugs. Increased serum levels of soluble Fas (sFas) are associated with a number of different disease states and with tumor progression and metastasis in patients. In this study, we examined the plasma levels of sFas in 94 women with metastatic breast cancer undergoing high-dose chemotherapy (HDCT) treatment with autologous stem cell transplantation (ASCT) using a quantitative enzyme-linked immunosorbent assay (ELISA) method. Thirty-one patients (31/94, 33%) had plasma sFas levels greater than the optimum cut point of 1.90 ng/ml (median 2.47, range 1.98-13.54 ng/ml) and were designated as sFas positive. Sixty-three patients (63/94, 67%) had sFas levels below 1.90 ng/ml (median 1.14, range 0.47-1.89 ng/ml). In univariate analysis, patients with sFas-positive status, HER-2 overexpression, and the presence of liver metastases had a significantly shorter time to disease progression (PFS) and significantly decreased overall survival (OS). Multivariable analysis (Cox proportional hazards model) for PFS determined that sFas status significantly predicted disease progression (p = 0.004) with an adjusted hazard ratio (HR) of 2.0 (95% CI, 1.3-3.3). HER-2 status and liver metastases were also significant independent predictors of disease progression (p < 0.001) for both. sFas level was also an independent prognostic factor for OS with an adjusted HR of 2.0 (p = 0.006; 95% CI, 1.2-3.4). HER-2 status and liver metastases also remained highly significant independent prognostic factors for OS (HER-2: P < 0.001, HR 2.3, and liver metastases: P = 0.001, HR 2.7). In conclusion, these results suggest that plasma levels of sFas may be a valuable clinical prognostic factor in predicting outcome (PFS and OS) for patients with metastatic breast cancer undergoing HDCT with ASCT.

Original languageEnglish
Pages (from-to)759-768
Number of pages10
JournalJournal of Hematotherapy and Stem Cell Research
Volume10
Issue number6
DOIs
StatePublished - Dec 1 2001
Externally publishedYes

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Stem Cell Transplantation
Breast Neoplasms
Neoplasm Metastasis
Drug Therapy
Disease Progression
Survival
Liver
Fas Ligand Protein
Proportional Hazards Models
Immune System
Neoplasms
Cell Death
Enzyme-Linked Immunosorbent Assay
Apoptosis
Serum
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Hematology
  • Immunology

Cite this

Soluble Fas (CD95) is a prognostic factor in patients with metastatic breast cancer undergoing high-dose chemotherapy and autologous stem cell transplantation. / Bewick, M.; Conlon, M.; Parissenti, A. M.; Lee, H.; Zhang, L.; Glück, S.; Lafrenie, R. M.

In: Journal of Hematotherapy and Stem Cell Research, Vol. 10, No. 6, 01.12.2001, p. 759-768.

Research output: Contribution to journalArticle

Bewick, M. ; Conlon, M. ; Parissenti, A. M. ; Lee, H. ; Zhang, L. ; Glück, S. ; Lafrenie, R. M. / Soluble Fas (CD95) is a prognostic factor in patients with metastatic breast cancer undergoing high-dose chemotherapy and autologous stem cell transplantation. In: Journal of Hematotherapy and Stem Cell Research. 2001 ; Vol. 10, No. 6. pp. 759-768.
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T1 - Soluble Fas (CD95) is a prognostic factor in patients with metastatic breast cancer undergoing high-dose chemotherapy and autologous stem cell transplantation

AU - Bewick, M.

AU - Conlon, M.

AU - Parissenti, A. M.

AU - Lee, H.

AU - Zhang, L.

AU - Glück, S.

AU - Lafrenie, R. M.

PY - 2001/12/1

Y1 - 2001/12/1

N2 - The Fas/Fas ligand (FasL) system plays an important role in cellular apoptosis and is involved in cancer cell death induced by the immune system and anticancer drugs. Increased serum levels of soluble Fas (sFas) are associated with a number of different disease states and with tumor progression and metastasis in patients. In this study, we examined the plasma levels of sFas in 94 women with metastatic breast cancer undergoing high-dose chemotherapy (HDCT) treatment with autologous stem cell transplantation (ASCT) using a quantitative enzyme-linked immunosorbent assay (ELISA) method. Thirty-one patients (31/94, 33%) had plasma sFas levels greater than the optimum cut point of 1.90 ng/ml (median 2.47, range 1.98-13.54 ng/ml) and were designated as sFas positive. Sixty-three patients (63/94, 67%) had sFas levels below 1.90 ng/ml (median 1.14, range 0.47-1.89 ng/ml). In univariate analysis, patients with sFas-positive status, HER-2 overexpression, and the presence of liver metastases had a significantly shorter time to disease progression (PFS) and significantly decreased overall survival (OS). Multivariable analysis (Cox proportional hazards model) for PFS determined that sFas status significantly predicted disease progression (p = 0.004) with an adjusted hazard ratio (HR) of 2.0 (95% CI, 1.3-3.3). HER-2 status and liver metastases were also significant independent predictors of disease progression (p < 0.001) for both. sFas level was also an independent prognostic factor for OS with an adjusted HR of 2.0 (p = 0.006; 95% CI, 1.2-3.4). HER-2 status and liver metastases also remained highly significant independent prognostic factors for OS (HER-2: P < 0.001, HR 2.3, and liver metastases: P = 0.001, HR 2.7). In conclusion, these results suggest that plasma levels of sFas may be a valuable clinical prognostic factor in predicting outcome (PFS and OS) for patients with metastatic breast cancer undergoing HDCT with ASCT.

AB - The Fas/Fas ligand (FasL) system plays an important role in cellular apoptosis and is involved in cancer cell death induced by the immune system and anticancer drugs. Increased serum levels of soluble Fas (sFas) are associated with a number of different disease states and with tumor progression and metastasis in patients. In this study, we examined the plasma levels of sFas in 94 women with metastatic breast cancer undergoing high-dose chemotherapy (HDCT) treatment with autologous stem cell transplantation (ASCT) using a quantitative enzyme-linked immunosorbent assay (ELISA) method. Thirty-one patients (31/94, 33%) had plasma sFas levels greater than the optimum cut point of 1.90 ng/ml (median 2.47, range 1.98-13.54 ng/ml) and were designated as sFas positive. Sixty-three patients (63/94, 67%) had sFas levels below 1.90 ng/ml (median 1.14, range 0.47-1.89 ng/ml). In univariate analysis, patients with sFas-positive status, HER-2 overexpression, and the presence of liver metastases had a significantly shorter time to disease progression (PFS) and significantly decreased overall survival (OS). Multivariable analysis (Cox proportional hazards model) for PFS determined that sFas status significantly predicted disease progression (p = 0.004) with an adjusted hazard ratio (HR) of 2.0 (95% CI, 1.3-3.3). HER-2 status and liver metastases were also significant independent predictors of disease progression (p < 0.001) for both. sFas level was also an independent prognostic factor for OS with an adjusted HR of 2.0 (p = 0.006; 95% CI, 1.2-3.4). HER-2 status and liver metastases also remained highly significant independent prognostic factors for OS (HER-2: P < 0.001, HR 2.3, and liver metastases: P = 0.001, HR 2.7). In conclusion, these results suggest that plasma levels of sFas may be a valuable clinical prognostic factor in predicting outcome (PFS and OS) for patients with metastatic breast cancer undergoing HDCT with ASCT.

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