RESUMEN
Further improvements in the treatment of breast cancer can be expected with a better understanding of its pathophysiology and through biologically-oriented therapeutic interventions, as well as better identification of patient populations likely to benefit from specific therapies. Trastuzumab (Herceptin) is the first biological modifier, showing significant activity in patients with advanced breast cancer who exhibit HER-2/neu gene amplification and/or protein overexpression. Trastuzumab is approved for use in combination with paclitaxel or docetaxel as first-line chemotherapy. Combinations of a taxane, a platinum salt and trastuzumab are feasible and active and have proven an increased survival advantage. This is in addition to the benefit that has been shown for Herceptin in combination with monochemotherapy alone. Several groups have demonstated the ratio of serum HER-2/neu levels prior to initiation of Herceptin treatment to levels at the time of re-staging examination to be significantly higher in patients with a significant benefit from therapy as compared to patients with progressive disease. As a result of the survival improvements in the metastatic setting, Herceptin was quickly entered into development trials for adjuvant treatment. The significant cardiac toxicity that has been observed with trastuzumab/anthracycline combinations has led to two main strategies for integrating trastuzumab in the adjuvant setting: either the addition of trastuzumab to mostly anthracycline-based programs in a sequential approach, or the biologically-oriented strategy based on synergism between trastuzumab and chemotherapy agents including platinum compounds. Last but not least, the most important prerequisite for the optimal efficacy of Herceptin-based therapy remains a very strict selection of those patients with tumours that have HER-2/neu over-expression.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/terapia , Inmunoterapia/métodos , Anticuerpos Monoclonales Humanizados , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/patología , Terapia Combinada , Humanos , Metástasis de la Neoplasia , TrastuzumabRESUMEN
BACKGROUND: Early detection before scintigraphic appearance of osseous metastatic spread might improve the outcome of breast cancer patients. The amino-terminal propeptide (PINP) of type I collagen as an indicator of bone formation is a very promising candidate among all markers of bone metabolism. We investigated the utility of total PINP in breast cancer patients at different stages of the disease. PATIENTS AND METHODS: Precision tests using controls and serum pools were done for total PINP on the Elecsys2010 analyzer (electrochemiluminescence immunoassay - ECLLA). Baseline samples of 51 breast cancer patients with metastatic disease plus 11 patients under neoadjuvant treatment were available. Altogether, 38 patients had been diagnosed with bone metastases while 24 had no evidence of metastatic spread to the bone. RESULTS: For serial precision (intra assay), we found coefficients of variation between 1.2-2%. Total imprecision according to the NCCLS protocol ranged from 1. 7-5.4% only. Retrieval in ring trials was between 94% and 103%. ROC analysis of osseous versus nonosseous metastatic disease revealed an area under the curve (AUC) of 0.72. The sensitivity for the detection of bone lesions was 50% at the preliminary normal cut-off of 95 ng/mL. The baseline levels of the patients with bone metastases were significantly higher than those of patients with visceral of soft tissue spread only (p<0.001). PINP concentrations correlated with osseous spread in terms of number and size of the bone lesions. Generally, non-osseous metastases did not produce elevated PINP levels in only 2/24 patients without bone metastases showing minimally elevated PINP concentrations (95 and 112 ng/ml). CONCLUSION: The Elecsys test for total PINP is highly reproducible. PINP concentrations can discriminate patients with bone metastases from those without osseous spread. The moderate sensitivity for the diagnosis of bone lesions may be biologically related to ineffective bone repair in a certain subset of patients. Further studies must focus on the monitoring of patients with elevated baseline levels and on those patients with low PINP levels in the case of otherwise proven bone metastases.
Asunto(s)
Biomarcadores de Tumor/sangre , Neoplasias Óseas/diagnóstico , Neoplasias de la Mama/patología , Fragmentos de Péptidos/sangre , Procolágeno/sangre , Adulto , Anciano , Neoplasias Óseas/secundario , Femenino , Humanos , Mediciones Luminiscentes , Persona de Mediana Edad , Curva ROCRESUMEN
INTRODUCTION: Tyrosine kinase signal transduction pathways are a focus of interest for therapeutic interventions. The oncoprotein HER-2/neu shows tyrosine kinase activity leading to phosphorylation and activation of numerous second-messenger systems. One target of phosphorylation processes is assumed to be the tumor type M2 isoenzyme of pyruvate kinase (TuM2-PK) which has been shown to be elevated in metastatic breast cancer. MATERIALS AND METHODS: We measured the plasma levels of HER-2/neu, TuM2-PK and tyrosine-phosphorylated TuM2-PK (p-TuM2-PK) in 69 patients (pts) with breast cancer and correlated these parameters to each other and to the classical tumor marker CA 27.29. The samples were measured with ELISA assays while CA 27.29 was determined with an automated chemiluminescence assay. For analysis, we formed 5 subgroups according to the plasma HER-2/neu levels (group 1: < 15 ng/ml, n = 28; group 2: 15 < or = x < 50 ng/ml, n = 21; group 3: 50 < or = x < 100 ng/ml, n = 9; group 4: 100 < or = x < 500 ng/ml, n = 7; group 5: > or = 500 ng/ml, n = 4). RESULTS: From the HER-2/neu group 1 to group 5, there was a statistically significant increase of CA 27.29 from 35.8 U/ml to 1095.8 U/ml (p < 0.001). There was also a trend for increasing TuM2-PK levels with increasing HER-2/neu levels (p = 0.126). From the lowest extinction (0.088) to the highest extinction result (2.167) of p-TuM2-PK we found a 25-fold increase, which was reproducible in spiking and dilution experiments proving that TuM2-PK is phosphorylated at tyrosine residues to a certain extent. However, there was no correlation between plasma HER-2/neu and p-TuM2-PK levels. CONCLUSION: TuM2-PK is phosphorylated at tyrosine residues in breast cancer patients. Using the shed antigen of HER-2/neu in plasma as a surrogate marker, we did not find any evidence that this phosphorylation is initiated by the oncoprotein HER-2/neu.
Asunto(s)
Neoplasias de la Mama/patología , Fosfotirosina/sangre , Piruvato Quinasa/sangre , Receptor ErbB-2/sangre , Adulto , Anciano , Antígenos de Carbohidratos Asociados a Tumores/sangre , Biomarcadores de Tumor/sangre , Neoplasias de la Mama/sangre , Femenino , Humanos , Isoenzimas/sangre , Persona de Mediana Edad , Estadificación de Neoplasias , Proteínas Tirosina Quinasas/sangre , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisisRESUMEN
We present our concept for treating patients suffering from recurrent sinusitis with coagulating lasers (Nd:YAG 1024 nm, Diode 810 or 904 nm). In these patients, the middle meatus is often narrowed by a hyperplastic middle turbinate, septum spurs and ridges, or by isolated polyps that block an ostium. We treat these patients by linear or punctate coagulation of the lateral wall of the middle turbinate, reducing the size of septum spurs, and blunting septal ridges or coagulating polyps. The outpatient procedure is performed with a laser fiberoptic system of 400 nm in contact mode with an energy of 3-5 watts. The amount of total energy applied to a specific tissue depends on the duration of laser contact at that point. The patient is anaesthesized superficially. Patients with a high degree of nasal hyperreactivity also receive antihistaminic preoperative treatment. Initial results show a significant increase of nasal flow with a decrease of sinus symptoms.