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Bruzas, Simona; Kuemmel, Sherko; Harrach, Hakima; Breit, Elisabeth; Ataseven, Beyhan; Traut, Alexander; Rueland, Anna; Kostara, Athina; Chiari, Ouafaa; Dittmer-Grabowski, Christine und Reinisch, Mattea (2021): Next-Generation Sequencing-Directed Therapy in Patients with Metastatic Breast Cancer in Routine Clinical Practice. In: Cancers, Bd. 13, Nr. 18, 4564

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Abstract

Simple Summary In earlier times, for patients with breast cancer who have metastases in distant organs, e.g., the lung, the mainstay of treatment was confined to chemotherapy. In recent years, additional therapeutic options have evolved as high-throughput commercial testing can identify alterations in genes, which are associated with cancer. Some of the identified genetic changes in each patient might be matched to a targeted therapy if the respective therapeutic agent is available. In this study, the implementation of this approach into routine clinical practice was investigated. All 95 patients with metastatic breast cancer had cancer-related genetic alterations, and, in 63 of them, these could be, in theory, matched to a genomically directed therapy. Out of 30 patients who were assigned to this therapy, 13 (43.3%) experienced an improved relapse-free period and 19 patients were still alive one year after molecular testing, in contrast to 15 out of 65 patients who received the standard therapy. Next-generation sequencing (NGS) followed by matched therapy has opened up new therapeutic options to patients with metastatic breast cancer (mBC). Here we report our experience with this approach in everyday clinical practice. This retrospective study included 95 patients with mBC who were genotyped with the FoundationOne (CDx) assay in a commercial molecular pathology laboratory. Genetic alterations were identified in all tumor specimens, and 83 patients (87.4%) had a median of 2 (range, 1-6) potentially actionable alterations. A multidisciplinary tumor board recommended genomically guided therapy to 63 patients, 30 of whom received such treatment. Everolimus (n = 15) and anti-human epidermal growth factor receptor 2 (HER2) therapy (n = 6) were most frequently administered. The ratio of progression-free survival (PFS) under NGS-based therapy to PFS under the last line of standard therapy prior to NGS was >1.3 in 13 (43.3%) patients, indicative of a clinical benefit to NGS-directed therapy. One-year overall survival rates were 22.7% (95% CI, 6.5-44.4) in 65 patients allocated to the standard therapy versus 62.9% (95% CI, 41.6-78.2) in 30 patients receiving the matched therapy. In conclusion, NGS-matched treatment improved the clinical outcomes in a subgroup of mBC patients.

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