1,721,007 research outputs found

    Petals and thorns in programmed death-ligand 1 testing: Is all non–small cell lung cancer diagnostic material suitable?

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    Russell-Goldman et al1 recently published in CancerCytopathology an article on the cytologic-histologiccorrelation of programmed death-ligand 1 (PD-L1)in lung carcinomas

    Tmb in nsclc: A broken dream?

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    Although immune checkpoint inhibitors have changed the treatment paradigm of a variety of cancers, including non-small-cell lung cancer, not all patients respond to immunotherapy in the same way. Predictive biomarkers for patient selection are thus needed. Tumor mutation burden (TMB), defined as the total number of somatic/acquired mutations per coding area of a tumor genome (Mut/Mb), has emerged as a potential predictive biomarker of response to immune checkpoint inhibitors. We found that the limited use of TMB in clinical practice is due to the difficulty in its detection and compounded by several different biological, methodological and economic issues. The incorporation of both TMB and PD-L1 expression or other biomarkers into multivariable predictive models could result in greater predictive power

    Palbociclib (PD 0332991): Targeting the cell cycle machinery in breast cancer

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    Introduction: The cyclin D-cyclin-dependent kinases 4 and 6 (CDK4/6)-retinoblastoma (Rb) pathway, governing the cell cycle restriction point, is frequently altered in breast cancer and is a potentially relevant target for anticancer therapy. Palbociclib (PD 0332991), a potent and selective inhibitor of CDK4 and CDK6, inhibits proliferation of several Rb-positive cancer cell lines and xenograft models. Areas covered: The basic features and abnormalities of the cell cycle in breast cancer are described, along with their involvement in estrogen signaling and endocrine resistance. The pharmacological features of palbociclib, its activity in preclinical models of breast cancer and the potential determinants of response are then illustrated, and its clinical development in breast cancer described. A literature search on the topic was conducted through PubMed and the proceedings of the main cancer congresses of recent years. Expert opinion: The combination of palbociclib with endocrine agents is a very promising treatment and Phase III clinical trials are ongoing to confirm its efficacy. Further, potentially useful combinations are those with drugs targeting mitogenic signaling pathways, such as HER2-and PI3K-inhibitors. Combination with chemotherapy seems more problematic, as antagonism has been reported in preclinical models. The identification of predictive factors, already explored in preclinical studies, must be further refined and validated in clinical trials. © 2014 Informa UK, Ltd

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Impressive long-term response with chemo-endocrine therapy in a premenopausal patient with metastatic breast cancer: A case report

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    RATIONALE: Patients with, or who develop, metastatic breast cancer have a 5-year relative survival of about 25%. Endocrine therapy clearly improves outcomes in patients with estrogen receptor-positive breast cancer. In the metastatic setting, the primary goal of treatment is to maintain long-term disease control with good quality of life. Rarely, exceptional responders achieve durable disease control, and potential cures cannot be ruled out. PATIENT CONCERNS: We report the case of a 39-year-old woman with primary breast cancer and associated synchronous bone metastases, who experienced a disease response of 12 years with hormonal therapy as maintenance after first line chemotherapy, with a good toxicity profile. DIAGNOSIS: The patient was diagnosed with estrogen receptor + human epidermal growth factor receptor 2 (HER2)- metastatic breast cancer with synchronous bone metastases. INTERVENTIONS: This patient was treated with chemotherapy for 6 cycles as a first-line therapy following by endocrine treatment given as a maintenance therapy. OUTCOMES: Our patient experienced a progression-free survival >12 years with an exceptionally good quality of life. LESSONS: Our anecdotal experience highlights the existence of exceptional responders among patients with hormone receptor-positive metastatic breast cancer, who achieve clinical remission and durable disease control with endocrine therapy. Being able to identify these patients could help in the selection of the best treatment option among the many available

    Are we ready to use TMB in breast cancer clinical practice?

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    We discussed the potentialities of tumor mutation burden (TMB) as a predictive marker for immunotherapy in breast cancer, also highlighting the limits that have hindered its introduction in the clinical practice. Although some studies have demonstrated the possibility to select patients more responsive to immune-checkpoint inhibitors by evaluating TMB, some issues emerged regarding the complexity of the methodologies for its determination, the costs of the analysis, and the necessity to improve the TMB determination with that of neoantigen identification
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