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Tennessee Ridge, TN, United States

Sorscher S.M.,University of Washington | Greco F.A.,Tennessee Oncology PLLC
Case Reports in Oncology

Cancer of unknown primary (CUP) is a clinical syndrome representing many types of cancers and diagnoses are typically made after review of clinical presentation, pathology (including immunohistochemical staining) and imaging studies. Treatment with systemic chemotherapy has been shown to result in fairly reproducible objective response rates. Herein, a case of a patient who was initially diagnosed with a poorly differentiated adenocarcinoma of unknown origin is reported. After mRNA gene expression profiling (commercially available CancerTYPE ID), a specific diagnosis of papillary renal cell carcinoma (RCC) was made and then confirmed with additional immunohistochemical staining. The patient was treated with targeted therapy and an objective radiographic response was seen. A literature review suggests this to be the first patient with papillary RCC, identified by molecular profiling, and benefitting from a targeted agent that otherwise would not have been considered in the setting of CUP. This case underscores the importance of considering the use of newer testing technologies in the interest of offering patients more specific, targeted therapy in order to improve efficacy and spare patients toxicities of less specific, empiric chemotherapeutic regimens. Copyright © 2012 S. Karger AG, Basel. Source

Shastry M.,Sarah Cannon Research Institute | Yardley D.A.,Sarah Cannon Research Institute | Yardley D.A.,Tennessee Oncology PLLC
Current Opinion in Obstetrics and Gynecology

Purpose of Review: Triple-negative breast cancer (TNBC) is clinically characterized by the lack of expression of the estrogen receptor/progesterone receptor and the human epidermal growth factor receptor 2. It is highly heterogeneous and exhibits considerable overlap with basal-like and BRCA-related breast cancers. Constituting 15-20% of breast cancers, TNBC exhibits an aggressive phenotype with a poor prognosis. This review summarizes recent progress and studies in TNBC and discusses some of the ongoing clinical trials and emerging therapies for the treatment of TNBC. Recent Findings: Conventional cytotoxic chemotherapy and DNA damaging agents continue to be the mainstay for treatment of this disease. The use of targeted agents such as bevacizumab, epidermal growth factor receptor and polyadenosine diphosphate-ribose polymerase inhibitors have led to conflicting results. However, recent research has prompted evaluation of additional drugs targeting multiple signaling pathways and epigenetic modifications for the treatment of this disease. Summary: TNBC remains a challenging disease to treat with recent trials having demonstrated only modest improvements in outcomes. Increased understanding of the heterogeneity of this complex subtype may help tailor therapies to specific patient subgroups. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source

Patients with cancer of unknown primary site (CUP) represent a clinical challenge since their diagnosis, classification, and management have been frustrating and difficult. Over the past several years, many more relatively specific immunohistochemical marker stains have been developed, and the field of gene expression profiling has emerged. With these improvements, the diagnosis of the likely primary tumor site is possible in many patients, providing an opportunity for site-specific or tailored treatment, rather than empiric therapy for all patients. Although more validation of the usefulness of molecular profiling assays is required in CUP, the approach to these patients has changed, and now there is a real prospect for improving patient outcomes. © 2010 Elsevier Inc. Source

Anthony Greco F.,Tennessee Oncology PLLC
Clinical Advances in Hematology and Oncology

Cancer of unknown primary site is a common clinico-pathologic syndrome representing a very heterogeneous group of patients with metastatic cancers and clinically undetectable primary tumor sites. The standard treatment for these patients for the last 15 years has been empiric "broad-spectrum" chemotherapy. In recent years, improved immunocytochemistry and the emergence of gene expression profiling have provided the diagnostic tools necessary to accurately define the tissue of origin in the majority of patients. Recent data have confirmed the ability of molecular profiling assays to complement standard pathologic diagnosis, and a large prospective study has documented a survival improvement for patients treated with site-specific therapy directed by the molecular assay diagnoses of their tissues of origin compared to empiric chemotherapy. The clinicopathologic evaluation of patients is now more standardized. The era of empiric chemotherapy administered to all patients is coming to an end, and customized therapies are favored. The management of patients has evolved with the ability to confidently define the tissue of origin. Further delineation of the molecular aberrations in advanced solid tumors, regardless of the primary tumor site, signals a more precise and perhaps more effective therapy for each patient. Source

Greco F.A.,Tennessee Oncology PLLC
Current Treatment Options in Oncology

Opinion Statement: Cancer of unknown primary site (CUP) is a clinicopathologic syndrome consisting of many types of cancer and accounting for approximately 3 % of all patients with advanced cancers. This syndrome has frustrated patients and physicians for decades, because a primary site or tissue of origin has not been possible to identify clinically, despite the presence of metastatic tumor. Favorable subsets (approximately 20 % of all CUP) with a presumptive occult primary site have been recognized for several decades based on clinical and standard pathologic features; site-specific therapy in these patients improves their survival compared with the majority of other (approximately 80 %) CUP patients. These other patients, most with adenocarcinomas, have been difficult to treat because the tissue of origin was unknown. Broad-spectrum empiric chemotherapy became the standard approach for these patients in the past 30 years. More recently, new diagnostic technology (evolving immunohistochemistry and emergent gene-expression profiling) has enabled us to establish accurately a tissue of origin in most (90 %+) CUP patients. Gene-expression profiling assays complement standard pathology and for the majority of biopsy specimens accurately identify the primary site or tissue of origin; clinical studies have supported the value of site-directed therapy. When the tissue of origin is in doubt after standard pathologic examination, a gene expression assay is frequently diagnostic, and the outcome of many CUP patients is improved with site-specific therapy. The era of empiric therapy has ended in favor of site-specific therapy, based on the precise diagnosis of the tumor type present in each patient. © 2013 Springer Science+Business Media New York. Source

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