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Clinical relevance of vascular endothelial growth factor and thymidine phosphorylase in patients with node-positive breast cancer treated with either adjuvant chemotherapy or hormone therapy.
Cancer J Sci Am. 1999 Mar-Apr; 5(2):101-11.CJ

Abstract

PURPOSE

To determine the role of the two angiogenic peptides, vascular endothelial growth factor (VEGF) and thymidine phosphorylase (TP) (the latter also being a target enzyme for cytotoxicity of 5-fluorouracil and methotrexate), and conventional prognostic factors in predicting relapse-free survival (RFS) and overall survival (OS) probabilities in two cohorts of patients with node-positive breast cancer (NPBC) treated with either adjuvant chemotherapy (CMF [cyclophosphamide, methotrexate, 5-fluorouracil] schedule) or hormone therapy (tamoxifen).

PATIENTS AND METHODS

We studied two groups of 137 and 164 patients with NPBC, median follow-up of 72 months for both, treated with adjuvant chemotherapy or hormone therapy, respectively. The cytosolic levels of VEGF and TP were determined in the primary tumor by original immunometric methods. The association between VEGF and TP and of these angiogenic peptides with other prognostic indicators were tested by using the Spearman correlation coefficient (for continuous variables) or the Kolmogorov-Smirnov test (for dichotomous variables). Results of the clinical outcome were analyzed by both univariate and multivariate (for RFS only) Cox regression models in which VEGF and TP were treated as continuous variables.

RESULTS

In the CMF group, the concentrations of VEGF and TP ranged from 5.8 to 7798 pg/mg of protein (median, 87.5 pg/mg) and from 1.2 to 904 U/mg (median, 138.2 U/mg), respectively. There was no significant association between the two angiogenic peptides. VEGF was not associated with any other variable, whereas TP showed a positive association with age and an inverse association with the number of involved nodes. In the tamoxifen group, the concentrations of VEGF (5.9-2482; median, 79.3 pg/mg protein) and TP (6.1-1542; median, 146.5 U/mg) were similar to those of the CMF group, and the two angiogenic peptides were not correlated. VEGF was positively associated with age and was inversely associated with estrogen receptor and progesterone receptor, whereas TP was not associated with any other variable. Univariate analysis in the CMF group showed that VEGF and TP were significantly predictive of both RFS and OS. Likewise, the number of involved axillary nodes was significantly associated with both RFS and OS. Univariate analysis in the tamoxifen group showed that TP did not significantly influence either RFS or OS. On the contrary, VEGF levels were significantly predictive of both RFS and OS, as were the number of involved nodes, estrogen receptor concentrations, and progesterone receptor concentration. In the multivariate analysis on RFS in the CMF group, VEGF, TP, their first-order interaction term, and age were significant and independent predictive factors. In the tamoxifen group, only VEGF and the number of involved nodes were significant and independent predictive factors.

DISCUSSION

The results of our study suggest that high levels of TP and low levels of VEGF characterize the patients with NPBC treated with adjuvant CMF who have the highest likelihood of favorable outcome. Low levels of VEGF and the presence of less than three involved axillary nodes characterize the patients with NPBC treated with adjuvant tamoxifen who have the highest likelihood of favorable outcome. This information may be useful to plan future studies to better select the patients with NPBC for conventional adjuvant treatments as well as to monitor the efficacy of novel therapeutic strategies of adjuvant therapy based on inhibition of angiogenesis.

Authors+Show Affiliations

Division of Medical Oncology, Azienda Ospedali Riuniti Bianchi-Melacrino-Morelli, Calabria, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10198732

Citation

Gasparini, G, et al. "Clinical Relevance of Vascular Endothelial Growth Factor and Thymidine Phosphorylase in Patients With Node-positive Breast Cancer Treated With Either Adjuvant Chemotherapy or Hormone Therapy." The Cancer Journal From Scientific American, vol. 5, no. 2, 1999, pp. 101-11.
Gasparini G, Toi M, Miceli R, et al. Clinical relevance of vascular endothelial growth factor and thymidine phosphorylase in patients with node-positive breast cancer treated with either adjuvant chemotherapy or hormone therapy. Cancer J Sci Am. 1999;5(2):101-11.
Gasparini, G., Toi, M., Miceli, R., Vermeulen, P. B., Dittadi, R., Biganzoli, E., Morabito, A., Fanelli, M., Gatti, C., Suzuki, H., Tominaga, T., Dirix, L. Y., & Gion, M. (1999). Clinical relevance of vascular endothelial growth factor and thymidine phosphorylase in patients with node-positive breast cancer treated with either adjuvant chemotherapy or hormone therapy. The Cancer Journal From Scientific American, 5(2), 101-11.
Gasparini G, et al. Clinical Relevance of Vascular Endothelial Growth Factor and Thymidine Phosphorylase in Patients With Node-positive Breast Cancer Treated With Either Adjuvant Chemotherapy or Hormone Therapy. Cancer J Sci Am. 1999 Mar-Apr;5(2):101-11. PubMed PMID: 10198732.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clinical relevance of vascular endothelial growth factor and thymidine phosphorylase in patients with node-positive breast cancer treated with either adjuvant chemotherapy or hormone therapy. AU - Gasparini,G, AU - Toi,M, AU - Miceli,R, AU - Vermeulen,P B, AU - Dittadi,R, AU - Biganzoli,E, AU - Morabito,A, AU - Fanelli,M, AU - Gatti,C, AU - Suzuki,H, AU - Tominaga,T, AU - Dirix,L Y, AU - Gion,M, PY - 1999/4/13/pubmed PY - 1999/4/13/medline PY - 1999/4/13/entrez SP - 101 EP - 11 JF - The cancer journal from Scientific American JO - Cancer J Sci Am VL - 5 IS - 2 N2 - PURPOSE: To determine the role of the two angiogenic peptides, vascular endothelial growth factor (VEGF) and thymidine phosphorylase (TP) (the latter also being a target enzyme for cytotoxicity of 5-fluorouracil and methotrexate), and conventional prognostic factors in predicting relapse-free survival (RFS) and overall survival (OS) probabilities in two cohorts of patients with node-positive breast cancer (NPBC) treated with either adjuvant chemotherapy (CMF [cyclophosphamide, methotrexate, 5-fluorouracil] schedule) or hormone therapy (tamoxifen). PATIENTS AND METHODS: We studied two groups of 137 and 164 patients with NPBC, median follow-up of 72 months for both, treated with adjuvant chemotherapy or hormone therapy, respectively. The cytosolic levels of VEGF and TP were determined in the primary tumor by original immunometric methods. The association between VEGF and TP and of these angiogenic peptides with other prognostic indicators were tested by using the Spearman correlation coefficient (for continuous variables) or the Kolmogorov-Smirnov test (for dichotomous variables). Results of the clinical outcome were analyzed by both univariate and multivariate (for RFS only) Cox regression models in which VEGF and TP were treated as continuous variables. RESULTS: In the CMF group, the concentrations of VEGF and TP ranged from 5.8 to 7798 pg/mg of protein (median, 87.5 pg/mg) and from 1.2 to 904 U/mg (median, 138.2 U/mg), respectively. There was no significant association between the two angiogenic peptides. VEGF was not associated with any other variable, whereas TP showed a positive association with age and an inverse association with the number of involved nodes. In the tamoxifen group, the concentrations of VEGF (5.9-2482; median, 79.3 pg/mg protein) and TP (6.1-1542; median, 146.5 U/mg) were similar to those of the CMF group, and the two angiogenic peptides were not correlated. VEGF was positively associated with age and was inversely associated with estrogen receptor and progesterone receptor, whereas TP was not associated with any other variable. Univariate analysis in the CMF group showed that VEGF and TP were significantly predictive of both RFS and OS. Likewise, the number of involved axillary nodes was significantly associated with both RFS and OS. Univariate analysis in the tamoxifen group showed that TP did not significantly influence either RFS or OS. On the contrary, VEGF levels were significantly predictive of both RFS and OS, as were the number of involved nodes, estrogen receptor concentrations, and progesterone receptor concentration. In the multivariate analysis on RFS in the CMF group, VEGF, TP, their first-order interaction term, and age were significant and independent predictive factors. In the tamoxifen group, only VEGF and the number of involved nodes were significant and independent predictive factors. DISCUSSION: The results of our study suggest that high levels of TP and low levels of VEGF characterize the patients with NPBC treated with adjuvant CMF who have the highest likelihood of favorable outcome. Low levels of VEGF and the presence of less than three involved axillary nodes characterize the patients with NPBC treated with adjuvant tamoxifen who have the highest likelihood of favorable outcome. This information may be useful to plan future studies to better select the patients with NPBC for conventional adjuvant treatments as well as to monitor the efficacy of novel therapeutic strategies of adjuvant therapy based on inhibition of angiogenesis. SN - 1081-4442 UR - https://www.unboundmedicine.com/medline/citation/10198732/Clinical_relevance_of_vascular_endothelial_growth_factor_and_thymidine_phosphorylase_in_patients_with_node_positive_breast_cancer_treated_with_either_adjuvant_chemotherapy_or_hormone_therapy_ L2 - http://www.diseaseinfosearch.org/result/960 DB - PRIME DP - Unbound Medicine ER -