Many nanosized particulate systems are being developed as intravascular carriers to increase the levels of therapeutic agents delivered to targets, with the fewest side effects. The surface of these carriers is often functionalized with biological recognition molecules for specific, targeted delivery. However, there are a series of biological barriers in the body that prevent these carriers from localizing at their targets at sufficiently high therapeutic concentrations. Here we show a multistage delivery system that can carry, release over time and deliver two types of nanoparticles into primary endothelial cells. The multistage delivery system is based on biodegradable and biocompatible mesoporous silicon particles that have well-controlled shapes, sizes and pores. The use of this system is envisioned to open new avenues for avoiding biological barriers and delivering more than one therapeutic agent to the target at a time, in a time-controlled fashion.

The goal of these guidelines, based on an expert consensus after careful review of published data, is to help the clinical diagnosis of this rare disease and to standardize management of IBC among treating physicians in both the academic and community settings.

Inflammatory breast cancer (IBC) is a rare and aggressive form of invasive breast cancer accounting for 2.5% of all breast cancer cases. It is characterized by rapid progression, local and distant metastases, younger age of onset, and lower overall survival compared with other breast cancers. Historically, IBC is a lethal disease with less than a 5% survival rate beyond 5 years when treated with surgery or radiation therapy. Because of its rarity, IBC is often misdiagnosed as mastitis or generalized dermatitis. This review examines IBC's unique clinical presentation, pathology, epidemiology, imaging, and biology and details current multidisciplinary management of the disease, which comprises systemic therapy, surgery, and radiation therapy. CA Cancer J Clin 2010;60:351-375.© 2010 American Cancer Society, Inc.To earn free CME credit or nursing contact hours for successfully completing the online quiz based on this article, go to http://CME.AmCancerSoc.org.Inflammatory breast cancer (IBC) is a clinicopathological entity characterized by rapid progression and aggressive behavior from onset of disease. Historically, its prognosis has been very grim. Especially before the introduction of systemic chemotherapy, attempts to control IBC with either surgery alone or surgery combined with radiation therapy resulted in median survival times of less than 15 months and local recurrence rates as high as 50%. 1 Although survival times have increased with multimodal therapy, they are still around 35% to 40% and much lower than those for other breast cancers. Because IBC is rare, clinicians are less familiar with it than with the more common types of noninflammatory breast cancers (non-IBC). The purpose of this review is to describe the clinical diagnosis, epidemiology, imaging, biology, and multidisciplinary treatment of IBC. We summarize both current practice and novel concepts under investigation.

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Background: Inflammatory breast cancer (IBC) is a poorly characterized form of breast cancer. So far, the results of expression profiling in IBC are inconclusive due to various reasons including limited sample size. Here, we present the integration of three Affymetrix expression datasets collected through the World IBC Consortium allowing us to interrogate the molecular profile of IBC using the largest series of IBC samples ever reported.Experimental Design: Affymetrix profiles (HGU133-series) from 137 patients with IBC and 252 patients with non-IBC (nIBC) were analyzed using unsupervised and supervised techniques. Samples were classified according to the molecular subtypes using the PAM50-algorithm. Regression models were used to delineate IBC-specific and molecular subtype-independent changes in gene expression, pathway, and transcription factor activation.Results: Four robust IBC-sample clusters were identified, associated with the different molecular subtypes (P < 0.001), all of which were identified in IBC with a similar prevalence as in nIBC, except for the luminal A subtype (19% vs. 42%; P < 0.001) and the HER2-enriched subtype (22% vs. 9%; P < 0.001). Supervised analysis identified and validated an IBC-specific, molecular subtype-independent 79-gene signature, which held independent prognostic value in a series of 871 nIBCs. Functional analysis revealed attenuated TGF-b signaling in IBC.Conclusion: We show that IBC is transcriptionally heterogeneous and that all molecular subtypes described in nIBC are detectable in IBC, albeit with a different frequency. The molecular profile of IBC, bearing molecular traits of aggressive breast tumor biology, shows attenuation of TGF-b signaling, potentially explaining the metastatic potential of IBC tumor cells in an unexpected manner. Clin Cancer Res; 19(17); 4685-96. Ó2013 AACR.