BACKGROUND: The vascular endothelial growth factor (VEGF) is a mediator of angiogenesis and is associated with cancer progression and poor prognosis in patients with primary breast cancer. VEGF is a heparin-binding glycoprotein that is secreted as a homodimer of 45Kda. Most types of cells, but usually not endothelial cells themselves, secrete VEGF. VEGF, particularly VEGF-A, increases vascular permeability, vasodilatation in endothelial cells and can also stimulate cell migration and inhibit apoptosis. We previously reported that elderly women with advanced breast cancer have high levels of VEGF and that correction of anaemia in these patients results in a relevant decrease of VEGF’s plasmatic levels. AIMS: According to these outcomes we would now investigate if variation of VEGF may also affects time to progression’s disease and fatigue that is a frequent symptom in elderly people with cancer. METHODS: VEGF concentrations were analyzed by an enzyme-linked immunosorbent assay (ELISA) in 79 volunteers (mean age: 70 yrs) and 84 elderly breast cancer patients stage III in EDTA plasma specimens. A dosage of 400-500 IU/Kg/t.i.w. of rHuEPO s.c. was administered in order to reach at less 13-14g/dl Hb. Level of serum iron was also adjusted to 24±2 μmol/L if necessary. All patients were treated with liposomal doxorubicin (75 mg/sqm) and cyclophosphamide (600 mg/sqm) every 3 weeks for 6 months. Time-to-progression (TTP) of disease and Fatigue was evaluated with Kaplan-Meyer formula and FACT and FACIT questionary respectively. VEGF was quoted at baseline, after Hb adjustment (a), at the end of therapy (aa) and after 18 months follow-up (aaa). RESULTS: 52 pts (A group) showed: VEGF(baseline): 607±21 pg/ml - VEGF(a): 512±19 pg/ml - VEGF(aa): 319±18 pg/ml - VEGF(aaa): 185±10 pg/ml - Hb (baseline) Mean Values (MV) were: 8.7±2 g/dl. 32 pts (B group) showed: VEGF(baseline): 216±31 pg/ml - VEGF(a): 204±20 pg/ml - VEGF(aa): 185±18 pg/ml - VEGF(aaa): 107±9 pg/ml - Hb (baseline) Mean Values (MV) were: 10.4±1.5 g/dl. Volunteers: VEGF 94±17 pg/ml - Hb 12.6±1.7 g/dl. TTP (A group): 11±1.5 mths - TTP (B group): 14±1.5 mths. Fatigue’s evaluation was as following: 50±10 (A group baseline) 70±10 (A group after HB adjustment) - 80±10 (B group) - 90±10 (Volunteers). CONCLUSION: These findings support a role for hypoxia and anaemia induced VEGF in human breast cancer and also suggest that adjustment of low Hb levels may lead to better results in cancer management through the abrogation of VEGF induced functions. Scrutiny of GJIC (gap junction intercellular communication) activity in human breast cancer cell lines by the Scrape-Loading/Dye Transfer (SL/DT) method in basic condition and after treatment with a specific VEGF-Ab is ongoing in order to confirm these preliminary considerations.
[Proc Amer Assoc Cancer Res, Volume 46, 2005]