Retrospective review of genomic testing in breast cancer: Does it improve outcome?

PURPOSE: Tumor genomic testing has become widely available in many clinical settings. However, we do not yet understand how to best harness the information yielded from this testing. We retrospectively investigated the clinical courses of 24 patients who underwent tumor genomic testing to determine whether targeted therapy is associated with improved progression free survival (PFS) compared to standard therapy. METHODS: The patient population comprised metastatic breast cancer patients who underwent tumor genomic testing (testing biopsy specimens of primary or metastatic lesions for 50 commonly mutated genes) at our institution between September 1, 2010 and June 1, 2015. Through retrospective chart review, we compared PFS for those patients who received targeted therapy based on their genomic testing results, and those who did not. RESULTS: The median PFS was 5.7 months for those who received targeted therapy versus 5.4 months for those who did not (p = 0.6). There was no statistically significant difference in PFS between the two groups. CONCLUSIONS: In this relatively small group, the PFS was markedly similar between the targeted therapy and standard therapy groups. Currently, there is no clear evidence to incorporate tumor genomic testing into routine clinical practice.

Fibronectin is essential for reparative cardiac progenitor cell response after myocardial infarction.

RATIONALE: Adoptive transfer of cardiac progenitor cells (CPCs) has entered clinical application, despite limited mechanistic understanding of the endogenous response after myocardial infarction (MI). Extracellular matrix undergoes dramatic changes after MI and therefore might be linked to CPC-mediated repair. OBJECTIVE: To demonstrate the significance of fibronectin (Fn), a component of the extracellular matrix, for induction of the endogenous CPC response to MI. METHODS AND RESULTS: This report shows that presence of CPCs correlates with the expression of Fn during cardiac development and after MI. In vivo, genetic conditional ablation of Fn blunts CPC response measured 7 days after MI through reduced proliferation and diminished survival. Attenuated vasculogenesis and cardiogenesis during recovery were evident at the end of a 12-week follow-up period. Impaired CPC-dependent reparative remodeling ultimately leads to continuous decline of cardiac function in Fn knockout animals. In vitro, Fn protects and induces proliferation of CPCs via ß1-integrin-focal adhesion kinase-signal transducer and activator of transcription 3-Pim1 independent of Akt. CONCLUSIONS: Fn is essential for endogenous CPC expansion and repair required for stabilization of cardiac function after MI.