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- SourceAvailable from: Pawel Domagala[Show abstract] [Hide abstract]
ABSTRACT: PURPOSE To estimate 10-year overall survival (OS) rates for patients with early-onset breast cancer, with and without a BRCA1 mutation, and to identify prognostic factors among those with BRCA1-positive breast cancer. PATIENTS AND METHODSA total of 3,345 women with stage I to III breast cancer, age ≤ 50 years, were tested for three founder mutations in BRCA1. Information on tumor characteristics and treatments received was retrieved from medical records. Dates of death were obtained from the vital statistics registry. Survival curves for the mutation-positive and -negative subcohorts were compared. Predictors of OS were determined using the Cox proportional hazards model. RESULTS Of the 3,345 patients enrolled onto the study, 233 (7.0%) carried a BRCA1 mutation. The 10-year survival rate for mutation carriers was 80.9% (95% CI, 75.4% to 86.4%); for noncarriers, it was 82.2% (95% CI, 80.5% to 83.7%). The adjusted hazard ratio (HR) associated with carrying a BRCA1 mutation was 1.81 (95% CI, 1.26 to 2.61). Among BRCA1 carriers with a small (< 2 cm) node-negative tumor, the 10-year survival rate was 89.9%. Among BRCA1 mutation carriers, positive lymph node status was a strong predictor of mortality (adjusted HR, 4.1; 95% CI, 1.8 to 8.9). Oophorectomy was associated with improved survival in BRCA1 carriers (adjusted HR, 0.30; 95% CI, 0.12 to 0.75). CONCLUSION The 10-year survival rate among women with breast cancer and a BRCA1 mutation is similar to that of patients without a BRCA1 mutation. Among women with a BRCA1 mutation, survival was much improved after oophorectomy.Journal of Clinical Oncology 08/2013; 31(26). DOI:10.1200/JCO.2012.45.3571
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ABSTRACT: Evaluation of FLT/PET/ CT usefulness in diagnosis and qualification for surgical treatment of gastric cancer. The FLT/PET/CT test was carried out in a group of 50 gastric cancer patients. Based on the test result, a decision followed about the therapeutic procedure to be applied. A comparison was made with regards to the consistency of the cancer growth advancement degree evaluation in the initial preoperative FLT/PET/CT test against the evaluation of postoperative degree of cancer advancement in histopathology. In the group of 50 diagnosed patients a surgical treatment was used for 37 patients. 21 resections were performed out of which 19 operations were radical In the group of 16 non-resective operations 2 post-laparotomic patients were selected for inductive treatment. In the group of 13 patients who did not undergo any surgery, 10 were directed to palliative care and 3 for inductive treatment. In the group of 50 patients, the applied FLT-PET/CT test confirmed presence of primary tumor in 49 patients. The presence of increased uptake of FLT in the local lymph nodes during the preoperative FLT-PET/CT test was confirmed in 22 cases. In 14 patients with FLT-PET/Ct N(+) with the M(-) feature resection surgery was performed. The increased uptake of FLT in localizing metastases (nodal and non-nodal) FLT-PET/CT (M+) was detected in 22 patients. The presence of nodal metastases in the postoperative histopathology examination (hpN+) was detected in 14 cases. In these cases preoperative FLT-PET/CT test proved the N(+) feature in 11 patients. The result FLT-PET/CT N(-) was truly negative in 2 patients, and false negative in 1 patient. In the group of 7 operated hpN(-) patients, in 3 patients a preoperative result FLT-PET/ CT N(+) (false positive result) was obtained. The consistency (positive) of nodal metastases identification in FLT-PET/CT as compared to post-surgical histopathology examination scored 11/15, which equals 73.3%. In the group of patients in whom resection surgery was performed, 4 false negative results were obtained [hp(N+), FLT-PET/CT (N-)] and 3 false positive results [hp(N-), FLT-PET/CT N(+)]. The initial test results indicate that FLT-PET/CT is an effective method in evaluating the primary tumor and the regional lymph nodes and is useful and beneficial in the diagnosis and further treatment evaluation of gastric cancer. FLT-PET/CT examination facilitates making proper therapeutic decisions - it allows the number of unnecessary laparotomies to be lowered.Contemporary Oncology / Wspólczesna Onkologia 04/2013; 17(2):165-170. DOI:10.5114/wo.2013.34621
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ABSTRACT: Background and Objective The rapid development of molecular biology techniques allows for the introduction of real-time polymerase chain reaction (PCR) methods with a limit of mutation detection at 1 % in a background of wild-type DNA. Analysis of KRAS mutations in codons 12, 13, and 61, together with analysis of BRAF mutations in codon 600, are predictive biomarkers for anti-epidermal growth factor receptor (EGFR) treatment in colorectal cancer. Our aim was to compare PCR methods for KRAS mutations and BRAF mutation analysis using DNA isolated from tissue samples previously evaluated for presence of tumor cells using a quantitative scale and the percentage of tumor cells (PTC) scale. We addressed the question of whether a low number of tumor cells can be qualified for somatic mutation testing. Results Our study showed that PTC as low as 10 % was good enough to detect KRAS G12D, G13D, and Q61L mutations in formalin-fixed paraffin-embedded (FFPE) material. Furthermore, our results indicate that up to 20 % of colorectal cancer may carry mutations in the KRAS codon 61 and BRAF codon 600, which suggests the value of these mutation analyses because patients carrying them are unlikely to respond to cetuximab or panitumumab. A low level of KRAS somatic mutation detection has not been studied in depth in the context of clinical outcomes in patients; therefore, we compared new PCR methods, (KRBR-RT 50 Entrogen; ViennaLab StripAssay) and re-evaluated KRAS and BRAF status in patients with relapse after targeted therapy. Conclusions The importance of molecular results was confirmed by clinical observation of a patient with relapse who had qualified for targeted therapy with KRAS WT status (but was diagnosed by less sensitive single-stranded conformation polymorphisms method). Interestingly, during anti-EGFR treatment, it came to the selection of cells with KRAS G12C mutation which were present from the beginning in the tumor but at a low level (detected by PCR methods) only and led consequently to the metastasis. Taking into consideration the limit of detection, labor time, and assay cost, the real-time PCR method seems to be very promising especially for FFPE material with the PTC below 15 %.Molecular Diagnosis & Therapy 04/2013; 17(3). DOI:10.1007/s40291-013-0025-8
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