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3509Background: The mutant allele fractions (MAFs) of a driver gene may influence response to matched targeted therapies, such as KRAS and anti-EGFR antibodies in CRC. We performed a comprehensive ...

e20582Background: Median age at diagnosis of lung cancer is 70 years (y) and approximately 45% of patients (pts) are 70y or older. No consensus guidelines for the management of these older pts exis...

537Background: Fibroblast growth factors (FGFs) and FGFRs play an essential role in cancer cell proliferation and survival, with FGFR1 and FGFR2 gene amplifications being the most frequent genomic ...

3602 Background: Biomarker-driven selection of new MTAs has not been widely successful in CRC as we reported in 2012. New screening platforms and drugs have reached early drug development. We aimed...

605 Background: To be eligible for an anti-HER therapy, tumors have to be HER2-positive as determined by IHC or in situ hybridization (ISH) analyses. Although gene amplification is generally consid...

4063 Background: AGC represents the third leading cause of cancer related deaths. Chemotherapy for AGC is active but still of limited efficacy and targeted agents Trastuzumab and Ramucirumab have s...

5562 Background: The broad spectrum of actionable molecular alterations (MA) detected with new techniques has increased interest in matched targeted therapies (MTT) after failure to standard treatm...

e18540 Background: Malignant pleural mesothelioma (MPM) frequently expresses elevated AKT/mTOR activity. Previous reports in gliomas, colon, breast and prostate cancer suggests that PTEN/PI3K pathw...

587 Background: BRAF mutation (mt) occurs in 5-8% of mCRC and its role as a negative prognostic factor is well known. The up-front detection of BRAF mt is not standardized beyond the boundaries of research. However, since novel emerging specific therapies are increasingly available in clinical trials, the prior determination of this mutation is now warranted. Methods: From 07/2010 to 01/2014, 581 patients (pts) with advanced refractory mCRCunderwent genetic tumor profiling as part of the VHIO Phase I Trial Molecular Prescreening Program. BRAF mt was determined by Sanger sequencing or multiplex PCR and mass detection (MassARRAY, Sequenom) of 268 frequent hotspots in 25 oncogenes including, KRAS, NRAS, and PIK3CA. PTEN status was also assessed by immunohistochemistry. Results: 581 samples were analyzed detecting BRAF mt in 56 (9.6%). In the BRAF mt population, median age was 61 years (45-80) and 54% had right-sided CRC. Metastatic sites were found at: liver 61%; peritoneum 52%; lung 39%. Median number of standard treatment was 4 (0-8) including cetuximab and/or panitumumab in 73%. BRAF V600E mutation was detected in 53 samples whereas V600K, D594V and D594G were seen in one sample each. PTEN was analyzed in 44.6% of samples resulting in low expression (H-score

5578 Background: In the wake of personalized medicine in Oncology, genetic tumor profiling has become a cornerstone to select patients (pts) for clinical trials, exploring new molecular targeted ag...

1509 Background: Women with a BRCA1 or BRCA2 mutation are at high risk of developing ovarian carcinoma (OC) and a residual risk of PC after PBSO has been reported. We aimed to analyze the incidence of PC after PBSO and the clinical, pathological and molecular risk factors associated to PC in our series. Methods: Between April 2005 and December 2012, 100 patients with BRCA1 or BRCA2 mutation (50 each) underwent PBSO and were followed in the High Risk Clinics for the development of PC. PBSO pieces were submitted to pathological examination for presence of pathological and molecular risk factors like in situ or invasive Fallopian Tube Carcinoma (isFTC, inFTC) and p53 signature. Patients’ medical charts included in the High Risk Clinics Database were revised retrospectively for clinical, pathological and molecular characteristics. We analyzed the incidence of PC and the odds ratio (OR) for PC after PBSO in univariate analysis. Results: Overall, 2 patients (2%, 1 BRCA1, 1 BRCA2) were found to have isFTC, while 5 out 34 had a positive p53 signature (15%, 1 BRCA1, 4 BRCA2). With a median follow-up of 40 months (1-90) since PBSO, 2 patients developed PC (2%, both BRCA2). They underwent PBSO at age of 63 and 64 years and developed the PC 2 and 9 years after. One had a history of isFTC with p53 signature and 5 children, while the other had a prior history of bilateral breast cancer and no children. None had a family history of OC. Performing PBSO at an age older than 50 years was associated with an OR 8.56 (3.29-22.27) of PC. Conclusions: Fifteen and 2% percent of our patients had a positive p53 signature or an occult isFTC in the PBSO piece. Our analysis suggests that delaying PBSO to women older than 50 years may be associated with a higher risk of PC. Further analysis in a larger cohort is warranted.