Adjuvant Docetaxel in Node-Negative Breast Cancer Patients: A Randomized Trial of AGO-Breast Study Group, German Breast Group, and EORTC-Pathobiology Group.

BACKGROUND: In node-negative breast cancer (NNBC), a high risk of recurrence is determined by clinico-pathological or tumor-biological assessment. Taxanes may improve adjuvant chemotherapy. METHODS: NNBC 3-Europe, the first randomized phase-3 trial in node-negative breast cancer (BC) with tumor-biological risk assessment, recruited 4146 node-negative breast cancer patients from 2002 to 2009 in 153 centers. Risk assessment was performed by clinico-pathological factors (43%) or biomarkers (uPA/PAI-1, urokinase-type plasminogen activator/its inhibitor PAI-1). High-risk patients received six courses 5-fluorouracil (500 mg/m2), epirubicin (100 mg/m2), cyclophosphamide (500 mg/m2) (FEC), or three courses FEC followed by three courses docetaxel 100 mg/m2 (FEC-Doc). Primary endpoint was disease-free survival (DFS). RESULTS: In the intent-to-treat population, 1286 patients had received FEC-Doc, and 1255 received FEC. Median follow-up was 45 months. Tumor characteristics were equally distributed; 90.6% of tested tumors had high uPA/PAI-1-concentrations. Planned courses were given in 84.4% (FEC-Doc) and 91.5% (FEC). Five-year-DFS was 93.2% (95% C.I. 91.1-94.8) with FEC-Doc and 93.7% (91.7-95.3) with FEC. Five-year-overall survival was 97.0% (95.4-98.0) for FEC-Doc and 96.6% % (94.9-97.8) for FEC. CONCLUSIONS: With adequate adjuvant chemotherapy, even high-risk node-negative breast cancer patients have an excellent prognosis. Docetaxel did not further reduce the rate of early recurrences and led to significantly more treatment discontinuations.

Prognostic assessment of PTK activity in T1-T2, N0-N1, M0 breast cancer: a multicentric retrospective study.

Protein tyrosine kinases (PTKs) play a major role in the transduction of intracellular mitogenic signal. PTKs are also involved in the process of cellular transformation. A number of studies have reported increased PTK activities in cytosolic fractions from human breast carcinoma. However, the possible pronostic value of these activities is difficult to establish from these studies, mostly conducted on limited numbers of patients. In order to clear up the issue, we have investigated a large series of patients with a long follow-up, using a retrospective multicentric study (894 breast cancers T1-T2, N0-N1, M0; median follow-up: 67 months). PTKs were measured using a radioenzymatic assay as described in our previously report. We confirmed the already observed correlation between PTK activities and Scarff-Bloom grading (p < 10(-5)), negative estrogen receptor (ER), and progesterone receptor (PR) status. By contrast, we found in this study a correlation between PTK values and clinical nodal status (p = 0.00027) not showed in our precedent analysis. In Cox multivariate analysis, PTK activity does not emerge as a significant pronostic parameter. On the other hand, tumor PTK activity assay may prove of great interest in clinical research using newly developed tyrosine kinase inhibitors in order to assess their biological impact and eventually to predict the responsiveness to these new therapeutic agents.

Deletions of chromosomes 1p and 19q are detectable on frozen smears of gliomas by FISH: usefulness for stereotactic biopsies.

Among diffuse gliomas, oligodendrogliomas may account for 25% of cases. They have a better prognosis and chemosensitivity as compared to astrocytomas. Genetic studies have shown a correlation between oligodendrocyte phenotype and presence of 1p/19q deletions. In addition, these deletions are of prognostic value. The aim of the present study was to describe a new method to detect 1p/19q deletions when little tumoral material is available (stereotactic biopsies (SBs)). Since smears (cytological preparations) are routinely done for intraoperative diagnosis of gliomas, we have searched for 1p/19q deletions by FISH in a series of 30 patients with a glioma. In 14 cases, loss of heterozygosity (LOH) analysis was also performed in order to validate our method. We found that FISH analysis on frozen smears was a simple, rapid and reliable method to detect 1p/19q deletions and a good concordance was found with LOH data (85%). The main advantages of FISH analysis on frozen smears are the following. First, it requires little material and can be easily done in the case of SBs. Second, it has a higher sensitivity than LOH especially in infiltrative areas of gliomas. Third, it allows detection of a codeletion 1p/19q in a single tumor cell. In contrast, LOH analysis is easier to interpret and can detect smaller and partial deletion whose pronostic significance remains to be defined. In conclusion, these two techniques can be used to investigate 1p/19q status in gliomas. The appropriate choice of one or other of these two techniques will depend on the specific questions that need to be answered.