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Fibroblastic growth factor receptor 1 amplification in osteosarcoma is associated with poor response to neo-adjuvant chemotherapy.

ABSTRACT: Osteosarcoma, the most common primary bone sarcoma, is a genetically complex disease with no widely accepted biomarker to allow stratification of patients for treatment. After a recent report of one osteosarcoma cell line and one tumor exhibiting fibroblastic growth factor receptor 1 (FGFR1) gene amplification, the aim of this work was to assess the frequency of FGFR1 amplification in a larger cohort of osteosarcoma and to determine if this biomarker could be used for stratification of patients for treatment. About 352 osteosarcoma samples from 288 patients were analyzed for FGFR1 amplification by interphase fluorescence in situ hybridization. FGFR1 amplification was detected in 18.5% of patients whose tumors revealed a poor response to chemotherapy, and no patients whose tumors responded well to therapy harbored this genetic alteration. FGFR1 amplification is present disproportionately in the rarer histological variants of osteosarcoma. This study provides a rationale for inclusion of patients with osteosarcoma in clinical trials using FGFR kinase inhibitors.

SUBMITTER: Fernanda Amary M

PROVIDER: S-EPMC4303166 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Fibroblastic growth factor receptor 1 amplification in osteosarcoma is associated with poor response to neo-adjuvant chemotherapy.

Fernanda Amary M M Ye Hongtao H Berisha Fitim F Khatri Bhavisha B Forbes Georgina G Lehovsky Katie K Frezza Anna M AM Behjati Sam S Tarpey Patrick P Pillay Nischalan N Campbell Peter J PJ Tirabosco Roberto R Presneau Nadège N Strauss Sandra J SJ Flanagan Adrienne M AM

Cancer medicine 20140527 4

Osteosarcoma, the most common primary bone sarcoma, is a genetically complex disease with no widely accepted biomarker to allow stratification of patients for treatment. After a recent report of one osteosarcoma cell line and one tumor exhibiting fibroblastic growth factor receptor 1 (FGFR1) gene amplification, the aim of this work was to assess the frequency of FGFR1 amplification in a larger cohort of osteosarcoma and to determine if this biomarker could be used for stratification of patients ...[more]

PMID: 24861215

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Project description:IntroductionThe essential goal of neoadjuvant chemotherapy (NACT) is to downstage the primary tumor making it amenable for breast conservation surgery (BCS). However, since the safety of this surgery is paramount, post-NACT breast conservation rates remain low. As per the recommendation of the 2018 Early Breast Cancer Trialists' Collaborative Group (EBCTCG) overview of long-term post-NACT follow-up, we have devised a protocol for imaging, localization, rad-path analysis, and documentation of radiotherapy techniques to ensure the safety of post-NACT breast conservation.MethodsThis is a retrospective cohort of 180 breast cancer patients who received NACT and were operated on by a single surgical oncologist from 2015 to 2020. After selection based on published guidelines, patients were treated with neoadjuvant systemic (chemo or hormone) therapy. In cases where primary tumors responded and reduced to 1-2 cm in size mid-NACT, the residual tumors were localized by clips under ultrasound guidance and calcification was wire localized. All patients were treated using appropriate surgical and oncoplastic techniques where indicated. Negative margins were ensured by intra-operative rad-path analysis. Adjuvant chemotherapy and radiotherapy were given as per protocol.ResultsIn 81 cases that required mastectomy at presentation, we were able to achieve a 72.8% post-NACT BCS rate with the help of oncoplasty. Overall, 142 of 180 (80%) patients were treated with breast conserving surgery of which 80% (121 of 142) were oncoplasty. Margins were assessed on intra-operative frozen and re-excised in the same setting. No positive margins were reported in final histopath of 142 breast conservation procedures. Post-operative complication rates after breast conservation in the first year were at 17% (24 of 142 including two major complications). Patient reported outcomes were satisfactory with increased satisfaction for breast conservation compared with immediate breast reconstruction.DiscussionEmploying oncoplastic breast surgery (OBS) techniques following stringent protocols for accurate localization of the residual tumor, intra-operative rad-path analysis, and adjuvant treatments, we show successful breast conservation in 72.8% of our mastectomy-qualified patients after downstaging by NACT. We also report satisfactory outcomes for post-NACT surgery, patient-reported satisfaction, and survival.

Project description:INTRODUCTION:MicroRNAs (miRNAs) are small non-coding RNA that plays a vital role in cancer progression. Neo-adjuvant chemotherapy (NAC) has become the standard of care for locally advanced breast cancer. The aim of this study was to evaluate miRNA alterations during NAC using multiple samples of tissue and serum to correlate miRNA expression with clinico-pathological features and patient outcomes. METHODS:Tissue and serum samples were collected from patients with locally advanced breast cancer undergoing NAC at four time points: time of diagnosis, after the first and fourth cycle of doxorubicin/cyclophosphamide treatment, and after the fourth cycle of docetaxel administration. First, we evaluated the miRNA expression profiles in tissue and correlated expression with clinico-pathological features. Then, a panel of four miRNAs (miR-451, miR-3200, miR-21, and miR-205) in serum samples was further validated using quantitative reverse-transcription polymerase chain reaction (RT-qPCR). The alterations in serum levels of miRNA, associations with clinical and pathological responses, correlation with clinico-pathological features, and survival outcomes were studied using Friedman, Mann-Whitney U, and Spearman, Wilcoxon signed-ranks tests. P?0.05 was considered statistically significant. RESULTS:We analyzed 72 tissue samples and 108 serum samples from 9 patients and 27 patients, respectively. MicroRNA expression profiling of tumor versus normal tissue revealed more than 100 differentially expressed miRNAs. Serum miR-451 levels were significantly decreased during treatment, and higher serum levels were associated with improved clinical and pathological responses and disease-free survival. This is one of the early reports on miR-3200 in response to treatment in breast cancer, as serum levels of miR-3200 found to decline during NAC, and higher serum levels were associated with lower residual breast cancer burden and relapse rates at time of diagnosis. CONCLUSION:Variations in serum miRNA levels during NAC treatment may be therapeutically significant for predicting response and survival outcomes.

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Fibroblastic growth factor receptor 1 amplification in osteosarcoma is associated with poor response to neo-adjuvant chemotherapy.

Publications

Fibroblastic growth factor receptor 1 amplification in osteosarcoma is associated with poor response to neo-adjuvant chemotherapy.

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