Gene expression profiling of inflammatory breast cancer

Abstract

BACKGROUND: Inflammatory breast cancer (IBC) is a rare but aggressive form of breast cancer. Despite multimodality treatment, the long‐term survival rate for patients with IBC has remained inferior at 50%. Until recently, IBC was understudied at the molecular level. Since 2004, new high‐throughput molecular profiling technologies have been applied to clinical samples with the aim of identifying genes or pathways potentially involved in disease development that may represent new, clinically relevant targets. METHODS: The authors conducted gene expression profiling studies of IBC clinical samples and investigated issues that may be addressed in the future to allow the “omics” approach to reach its full potential in IBC. RESULTS: Starting in December 2004, 6 research groups compared the expression profiles of IBC samples and non‐IBC samples. The series of samples were small (37 IBCs for the largest study) and heterogeneous (various tumor selection criteria and technologic platforms were used). The results indicated the feasibility of messenger RNA expression profiling from IBC biopsies, and they demonstrated the great transcriptional heterogeneity of IBC and the existence of molecular subtypes similar to non‐IBC that more frequently were basal and positive for ERBB2. Supervised analyses demonstrated differences in gene expression levels between the IBC and non‐IBC variable across studies with sometimes no or very subtle differences and, to date, no gene overlap across the reported signatures. No signature predictive of therapeutic response or clinical outcome has been reliably identified or validated. CONCLUSIONS: Because of the great heterogeneity of IBC, future studies will have to include larger series of IBC samples that are selected using homogeneous criteria. This calls for urgent international collaborations. Cancer 2010;116(11 suppl):2783–93. © 2010 American Cancer Society.

Regulation of Inflammatory Breast Cancer Cell Invasion through Akt1/PKBα Phosphorylation of RhoC GTPase

“…The differences in Akt function between IBC and nIBC are not surprising. Research over the past decade has repeatedly showed that IBC has a unique molecular profile and uses alternate signaling pathways (27,29,42). This research has also previously implicated the PI3K pathway in IBC patient samples (43).…”

MicroRNA expression profiling identifies decreased expression of miR-205 in inflammatory breast cancer

“…The few published mRNA expression profiling studies to date have indicated that transcriptional heterogeneity exists in inflammatory breast cancer as extensively as in noninflammatory breast cancer, and that the established molecular subtypes such as luminal, HER2-positive, and basal-type can be identified in inflammatory breast cancer. [5][6][7][8][9][10][11][12][13][14][15][16] Although some of the studies have demonstrated differences in mRNA expression levels between inflammatory breast cancer and noninflammatory breast cancer samples, a specific inflammatory breast cancer signature cannot be deduced from these studies.…”

Expression Profiling of Breast Tumors Based on Human Epidermal Growth Factor Receptor 2 Status Defines Migration-Related Genes

“…Microarray experiments for breast cancer tumors have been carried out widely, but expression profiling of breast tumor classification based on HER2 status has only been performed in a few studies [15,16,17]. Expression profiling in breast tumors could facilitate progress on HER2 typing, allowing a better classification of tumors, the identification of undiscovered oncogenic pathways or the prediction of outcome or response to therapy.…”

“…They defined a small core region of coexpressed genes which are also probably coamplified, although the regulatory mechanisms leading to this overexpression remain unclear. Furthermore, the expression profiles of these genes could play an important role in the outcome of patients [14] and various gene expression signatures containing several 17q genes have been reported [7,15,16,17,18,33,34]. It is evident that the HER2-amplicon is variable and that it includes other upregulated genes located on 17q, such as TOP2A, CDC6, RPL19 which are not included in our chromosome-17-specificsignature.…”

“…In addition, different gene signatures obtained from the analysis of cDNA microarray data, such as the 70-gene MammaPrint signature [11] and the 76-signature [12], might provide prognostic information, as well as help to individualize treatments in the increasing breast cancer population [13,14]. However, few studies have focused on the comparison of expression profiles between patients with different HER2 status according to IHC and FISH scores [15,16,17,18]. This is surprising, since breast cancer patients are classified in the clinic on the basis of HER2 status, and the role of HER2 in the oncogenesis remains unclear [19].…”