High tumor levels of vascular endothelial growth factor predict poor response to systemic therapy in advanced breast cancer (original) (raw)
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Cancer Research
Vascular endothelial growth factor (VEGF), a potent angiogenic factor, has been reported to be associated with a poor prognosis in primary breast cancer and in several other cancer types. In the present study, we have measured with ELISA the levels of VEGF in cytosolic extracts of 845 primary breast tumors of patients who developed a recurrence during follow-up. All of the patients received tamoxifen (n ؍ 618) or cyclophosphamide, methotrexate, 5-fluorouracil (CMF) or 5-fluorouracil, Adriamycin, cyclophosphamide (FAC) chemotherapy (n ؍ 227) as first-line systemic therapy after diagnosis of advanced disease. VEGF levels were not related to age or menopausal status but were negatively related to the cytosolic levels of estrogen receptor and progesterone receptor (P < 0.0001). In patients who relapsed within 1 year after primary surgery, tumor VEGF levels were higher than in patients who showed a longer disease-free interval (P ؍ 0.0005). In patients with a first relapse in the viscera, VEGF levels were higher compared with those that relapsed to the bone or soft tissue (P ؍ 0.0004). In univariate analysis for response to first-line tamoxifen therapy, patients with high or intermediate levels showed a poor rate of response, compared with patients with low tumor-VEGF levels (P ؍ 0.0001). Similarly, in multivariate analysis for response to tamoxifen treatment, corrected for age, site of relapse, disease-free interval, and estrogen receptor and progesterone receptor status, VEGF status was an independent predictive factor (P ؍ 0.009). In concordance, higher levels of VEGF were associated with a short progression-free survival and postrelapse overall survival (both, P < 0.0001). On first-line chemotherapy, the rate of response decreased with higher tumor levels of VEGF, both in univariate (P ؍ 0.003) and in multivariate analysis (P ؍ 0.004). Furthermore, higher VEGF levels were associated with a short progression-free survival (P ؍ 0.003) and postrelapse overall survival (P ؍ 0.001). In conclusion, the tumor VEGF level is an important independent marker that predicts a poor efficacy of both tamoxifen and chemotherapy in advanced breast cancer. Knowledge of the tumor level of VEGF might be helpful in selecting individual patients who may benefit from treatments with antiangiogenic agents combined with conventionally used drugs.
Cancer research, 2000
The assessment of angiogenesis in breast cancer is of importance as a key indicator of survival and response to therapy. Circulating vascular endothelial growth factor (VEGF) measurements may provide a less subjective analysis than microvessel density (MVD) or immunohistochemical analysis of VEGF expression; however, most studies have used serum, which is now known to largely reflect platelet-derived VEGF concentrations. This study examined for the first time both plasma (VEGFp) and serum (VEGFs) VEGF concentrations in 201 blood samples from pre- and postmenopausal healthy controls and from patients with benign breast disease, localized breast cancer, breast cancer in remission, or metastatic breast cancer and related these to other clinicopathological markers. VEGFp but not VEGFs concentrations of patients with localized disease were significantly elevated compared with normal controls (P = 0.016). Patients with metastatic disease had higher VEGFp and VEGFs levels than normal contr...
Polish Journal of Pathology, 2012
The aim of the study was to assess the value of vascular endothelial growth factor (VEGF) measurements in breast cancer patients with respect to recognized clinicopathological prognostic factors. The study was conducted in 87 women with histologically confirmed breast cancer who underwent surgical treatment and 37 healthy women. Vascular endothelial growth factor concentration levels in the blood samples of patients were correlated with the size of the primary tumor, lymph nodes in the armpit, cancer stage, histological type, grading, multifocality, status of estrogen and progesterone receptors and HER-2 protein expression. Statistical analysis did not show any correlation between concentrations of VEGF and any of the selected parameters. The comparison of VEGF concentrations showed a slightly raised level of VEGF in women with the disease as opposed to the healthy subjects but the differences were not statistically significant (p = 0.472). Similar results were obtained for marker CEA (p = 0.09), while the level of Ca 15-3 in both groups differed significantly (p < 0.001) reaching higher values in the patients with diagnosed breast cancer. Vascular endothelial growth factor concentrations in breast cancer patients do not correlate with recognized clinicopathological prognostic factors and CEA and Ca 15-3 markers, which does not preclude the potential role of VEGF as an independent prognostic factor.
The International Journal of Biological Markers, 2004
VEGF is a specific mitogen and survival factor for endothelial cells and a key promoter of angiogenesis in physiological and pathological conditions. Nevertheless, VEGF tissue evaluation in cancer patients as a prognostic factor compared to the conventional histological and biological parameters is still controversial. In this case-control study, tissue VEGF was retrospectively determined by immunohistochemistry and related to T, N, ER, PgR, c-erbB-2, p53, MIB-1 and cyclin D1 in 129 breast cancer patients. Seventy-four of these patients had developed distant metastases postoperatively. The remaining 55 patients had remained disease-free >10 years after surgery. In 17 (13%) of the 129 patients (six with distant metastases and eleven disease-free) tissue and plasma VEGF were concomitantly evaluated. In univariate analysis no significant differences in VEGF and tumor size were found between metastatic and disease-free patients, whereas there were significant differences in N, ER, PgR, c-erbB-2, p53, MIB-1 and cyclin D1 (p ranging from 0.001 to 0.0001). In multivariate analysis VEGF showed less significance than N, ER, c-erbB-2, MIB-1 and cyclin D1 (p=0.012, p=0.007, p=0.005, p=0.005, p=0.002 and p=0.001, respectively). VEGF was a significant unfavorable prognostic indicator only in the N+ subset (p=0.015), while ER (p=0.05 and p=0.021) and MIB-1 (p=0.031 and p=0.022) were significant in both the N+ and N-subgroups. In multivariate analysis in the 74 metastatic cases VEGF did not show any significance in relation to disease-free interval and overall survival from the time of mastectomy and from the time of relapse, whereas N and PgR did (p ranging from 0.018 to 0.001). In conclusion, tissue VEGF does not seem a suitable candidate to replace conventional histological and other common biological prognostic factors in breast cancer.
International Journal of Cancer, 1997
Studies have shown that microvessel density influences breast-cancer prognosis. Since tumor angiogenesis is considered to be substantially affected by the excretion of vascular endothelial growth factor (VEGF) from tumor cells, we examined whether VEGF concentration is different in malignant and in non-malignant breast tissue. It was also of interest to discover whether intratumoral VEGF concentration influences disease-free survival (DFS) of breast-cancer patients. Analysis is based on 120 tissue specimens taken from breast fibromas (n 5 23), normal epithelial breast tissue adjacent to fibromas (n 5 8) and invasive breast cancer (n 5 89). VEGF concentration was quantified by using an immunoassay. Microvessel density was determined by immunostaining for factor-VIII-related antigen. Median VEGF concentration is given in pg/mg protein (25%-quantile-75%-quantile) and it was 0 (0-1.8) in normal breast tissue, 9.8 (0.52-43.0) in fibromas and 130.4 (50.8-362.2) in invasive carcinomas. A univariate Cox model revealed that node status, tumor size, estrogen-receptor concentration, histological grading and microvessel density were prognostic factors for disease-free survival in breast cancer. We found a significant correlation between VEGF concentration and microvessel count, but VEGF concentration did not significantly influence diseasefree survival. Although VEGF protein was found at a significantly higher concentration in malignant than in nonmalignant tissue, determination of intratumoral VEGF protein by an enzyme immunoassay was not prognostically relevant in our patient population. Int. J. Cancer 74:455-458, 1997.
Vascular endothelial growth factor –A (VEGF-A) expression as a prognostic factor in breast cancer
IP innovative publication pvt ltd, 2020
Objective: To assess the expression of VEGF-A in breast cancer patient and to find an association between VEGF- A overexpression and the clinicopathologic features. Materials and Methods: The study was conducted from January 2010 through 2016. Formalin-fixed, paraffin-embedded blocks from 64 patients with breast cancer were included in this study. S treptavidinbiotin method was employed for immunohistochemical detection of VEGF. Results: The detection rate of VEGF was 93.5%. There was a significant difference in the immunoexpression of VEGF A between the different histological types of carcinoma. However, no significant differen ces were noted among age groups, tumor sizes, perineural invasion and overall survival. Conclusion: In our study, VEGF overexpression was positiv ely associated with only the histological type of breast cancer. Further studies involving patients with advanced diseases are required to establish an association between the VEGF-A over expression and survival outcomes and to use it as a prognostic biomarker.
Clinical Breast Cancer, 2003
This study was designed to investigate the possible relationship between the protein expression of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) with p53 status, breast cancer prognostic factors, metastatic site, and survival after adjuvant therapy. Basic fibroblast growth factor and VEGF expression were determined by enzyme-linked immunosorbent assays in cytosol specimens obtained from 1307 patients with T1-3 primary breast cancer (789 node-negative, 518 node-positive) diagnosed between 1990 and 1997. The median follow-up time was 70 months. Increased bFGF expression was more frequently found in tumors with low VEGF expression (r = -0.286; P = 0.095). Increased bFGF was associated with smaller tumors (P < 0.001), absence of axillary metastasis (P = 0.003), low S-phase fraction (P < 0.001), and longer recurrencefree survival (RFS; P = 0.0038) and overall survival (OS; P = 0.0316). Vascular endothelial growth factor was a prognostic factor for RFS (P < 0.0001) and OS (P < 0.0001) in univariate and multivariate analyses (RFS: 95% CI, 1.1-1.7; P = 0.036; OS: 95% CI, 1.2-2.2; P = 0.002), whereas bFGF expression was not correlated with RFS or OS. Increased VEGF content was correlated with shorter survival after adjuvant endocrine therapy (RFS, P = 0.0004; OS, P = 0.0009). Patients with estrogen receptor-negative disease were excluded from the analysis. Basic fibroblast growth factor was not a prognostic factor after adjuvant systemic therapy, nor was it related to metastatic site. Expression of VEGF is an independent prognostic factor for patients with primary breast cancer. High bFGF expression was related to good prognostic features and longer survival times, but did not add prognostic information in multivariate analysis. The results might implicate that different angiogenic pathways exist in human breast cancer.
British journal of cancer, 1999
The aim of this study was to determine the association of vascular endothelial growth factor (VEGF) content in 302 consecutive node-negative breast cancer (NNBC) patients treated with only locoregional radiotherapy to relapse free- (RFS) and overall survival (OS). VEGF content in tumour cytosols was measured by an enzymatic immunoassay for the major isoform VEGF165. The median age was 56 years, the median follow-up time 56 months. A wide range (0.01-144.79 pg microg(-1) DNA) of VEGF content was found (median 1.92). Significant associations were found between VEGF and oestrogen receptor (ER) content, progesterone receptor (PR) and tumour size (P = 0.005). Univariate analysis displayed significant reduced RFS and OS for patients with higher VEGF content (P = 0.0113 and P = 0.0075 respectively). A total of 43 recurrences have been found (ten local relapses within the breast, five in the axillary or supraclavicular lymph nodes and 28 distant metastasis). There was no significant correla...
Plasma VEGF as a Marker of Therapy in Breast Cancer Patients
Introduction: Angiogenesis, the process leading to the formation of new blood vessels from a preexisting vascular network, is necessary for tumor growth, invasion, and metastasis. Vascular endothelial growth factor (VEGF) is one of the most potent angiogenic cytokines. Since blood biomarkers are minimally invasive, relatively easy to evaluate, we investigated the prognostic significance of plasma VEGF in Breast cancer patients. Methods: Preoperative plasma VEGF levels were determined by enzyme-linked immunosorbant assay in 80 women with breast cancer and in 80 normal female controls Results: There was a significant (P<0.001) increase in plasma VEGF level in breast cancer patients (Mean± SD 136.22±9.95) compared with controls(61.88±6.19). Our study showed that increased plasma VEGF levels were significantly associated with menopausal status, clinical stage of disease and hormone receptor status. Conclusion: Since the increased plasma VEGF levels were associated with menopausal status, clinical stage of disease and hormone receptor status, it can be used a possible surrogate pharmacodynamic marker for determining the optimal biological dose of antibody drugs.