The understanding and management of membranous nephropathy, a common cause of nephrotic syndrome that is more frequently encountered in adults than in children, has rapidly evolved over the past decade. Identification of target antigens has allowed for more precise molecular diagnoses, and the ability to monitor circulating autoantibodies has added a new vantage point in terms of disease monitoring and decisions about immunosuppression. Although immunosuppression with alkylating agents combined with corticosteroids, or with calcineurin inhibitor-based regimens, has been the historical mainstay of treatment, observational and now randomized controlled trials with the B-cell-depleting agent rituximab have moved this agent to the forefront of therapy for primary membranous nephropathy. In this Core Curriculum, we discuss the typical features of primary and secondary disease; highlight the target antigens such as the phospholipase A 2 receptor, thrombospondin type 1 domain-containing 7A, neural epidermal growth factor-like 1, and semaphorin-3B; describe the relationship between the immunologic and clinical courses of disease; and review modern management with supportive care or immunosuppressive treatment based on these composite parameters.Complete author and article information provided at end of article.

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e13023 Background: Targeted cancer therapy has been posited to revolutionize treatment paradigms in oncology. There are, a paucity of data regarding the use of NGS in breast cancer (BC). Herein we report our experience with NGS in a consecutive series of BC patients. Methods: Using an IRB approved protocol, we retrospectively identified patients with BC treated at the Sylvester Comprehensive Cancer Center (UMMSOM) who underwent NGS. Data were collected on demographics, tumor characteristics, genomic mutation profiles, and subsequent response to targeted therapy after 3 months. Results: Between January 2013 and April 2016, 101 BC patients underwent NGS. The mean age at diagnosis was 49. Ninety-one percent were stage IV, 6% were stage III, 2% were stage II, and 1% were stage I. Fifty percent had estrogen receptor (ER)+, HER2- tumors, 31% had triple-negative tumors, 13% had HER2+, ER+ tumors, and 6% had HER2+, ER- tumors. Ninety-six percent had at least one mutation, of which 78% had a targetable mutation. Sixteen patients received targeted therapy (TT). The average time between NGS and TT was 5 months ranging 0-22 months, during which seven patients received other systemic therapy. The most common reasons for not receiving TT were no actionable mutations (24%), not meeting criteria for an available clinical trial (14%), stable disease (SD) (13% ), lost to follow up (11%), physician decision (11%). Of the 16 patients who received TT, 7 patients had progression of disease, 3 died before response could be evaluated and presumably had no benefit, 2 discontinued TT due to side effects, 1 had SD, 1 had a partial response, and 2 were too early to be assessed. Conclusions: The majority of BC patients in our series had actionable mutations. However, TT was not offered to a significant number of patients for a multiplicity of reasons and the clinical benefit in those patients treated according to NGS findings was dismal. While NGS is surely a promising technology that should be utilized in combination with molecular tumor board, a host of reasons limit its usefulness at this time and its expense may well not justify its use outside of clinical trials.