First-line bevacizumab in combination with chemotherapy for HER2-negative metastatic breast cancer: pooled and subgroup analyses of data from 2447 patients.

BACKGROUND: Bevacizumab has consistently demonstrated improved progression-free survival (PFS) and response rate when combined with first-line chemotherapy for HER2-negative metastatic breast cancer (mBC). However, the lack of a significant overall survival (OS) difference continues to attract debate, and identification of patients deriving greatest benefit from bevacizumab remains elusive. PATIENTS AND METHODS: Individual patient data from three randomised phase III trials in the first-line HER2-negative mBC setting were analysed, focusing specifically on efficacy in poor-prognosis patients. RESULTS: The meta-analysis (n = 2447) demonstrated a PFS hazard ratio (HR) of 0.64 (95% confidence interval [CI] 0.57-0.71; median 9.2 months with bevacizumab versus 6.7 months with non-bevacizumab therapy) and response rate of 49% versus 32%, respectively. The OS HR was 0.97 (95% CI 0.86-1.08); median 26.7 versus 26.4 months, respectively. In patients with triple-negative mBC, the HRs for PFS and OS were 0.63 (95% CI 0.52-0.76) and 0.96 (95% CI 0.79-1.16), respectively. Median PFS was 8.1 months with bevacizumab versus 5.4 months with chemotherapy alone, median OS was 18.9 versus 17.5 months, respectively, and 1-year OS rates were 71% versus 65%. CONCLUSIONS: Bevacizumab improves efficacy, including 1-year OS rates, both overall and in subgroups of poor-prognosis patients with limited treatment options.

Significant correlation of matrix metalloproteinase and macrophage colony-stimulating factor serum concentrations in patients with head and neck cancer.

Serum matrix metalloproteinases (MMPs) and the macrophage colony-stimulating factor (M-CSF) are of potential interest as serum tumor markers in various malignancies. There is still a lack of reliable tumor markers in patients with squamous cell carcinoma of the head and neck (SCCHN). Therefore, the tumor marker potential of MMPs and M-CSF was investigated in these malignancies. Serum of 59 patients suffering from SCCHN and of 59 healthy volunteers was obtained. The concentration of MMP-3, MMP-8, MMP-9, and M-CSF was determined by sandwich enzyme immunoassays. The MMP- 3, -8, -9, as well as the M-CSF serum concentrations were significantly elevated in the patient group, compared to the healthy controls (p<0.001, p<0.05, p<0.001, p=0.002). There was significant correlation between the M-CSF and the MMP-3 serum concentration (p<0.0001), and between the M-CSF and the MMP-8 serum concentration (p=0.005). A significant correlation with the tumor stage was found only for MMP-8. MMP and M-CSF serum concentrations are of potential interest as serum tumor markers in SCCHN.

Functional anatomy of lymphatic vessels under the aspect of tumor invasion.

In the human body there are about 800 lymph nodes, of which 300 are located in the head and neck area. The lymphatic system begins with initial finger-shaped lymphatic vessels consisting of valveless lymphatic capillaries and precollectors with valves. The precollectors become collectors and transport the lymph to the so-called lymph stems. These vessels lead into the right and left lymphatic duct and into the jugular trunk of the head and neck region. At the end they join into the blood circulation at the junction point of the jugular and subclavian veins. On the basis of the morphology of the initial lymphatics, these are probably the main port of entry of tumor cells. Investigations demonstrate the active invasion into the lymphatic system of melanoma cells. The preference of melanoma cells to adhere to the extracellular fibronectin of the endothelial cells may be a reason for the privileged invasion of the melanoma cells in the lymphatic system, because the extracellular matrix is not protected by a continuous basal lamina like blood vessels. Based on the directed movement of melanoma cells towards the fiber felt, there might be regulative mechanisms influencing the process of targeted adhesion.