Inflammatory breast cancer (IBC) is the most lethal form of primary breast cancer. IBC lethality derives from generation of tumour emboli, which are non-adherent cell clusters that rapidly spread by a form of continuous invasion known as passive metastasis. In most cancers, expression of E-cadherin, an epithelial marker, is indicative of low metastatic potential. In IBC, E-cadherin is overexpressed and supports formation of tumour emboli by promoting tumour cell interactions rather than adherence to stroma. E-cadherin, a surface component of adherens junctions, is anchored by interaction with p120 catenin (p120). We show that the unique pathogenic properties of IBC result in part from overexpression of the translation initiation factor eIF4GI in most IBCs. eIF4GI reprograms the protein synthetic machinery for increased translation of mRNAs with internal ribosome entry sites (IRESs) that promote IBC tumour cell survival and formation of tumour emboli. Overexpression of eIF4GI promotes formation of IBC tumour emboli by enhancing translation of IRES-containing p120 mRNAs. These findings provide a new understanding of translational control in the development of advanced breast cancer.

Optical coherence tomography is a simple, portable, promising modality for evaluation of bladder lesions and depth of tumor penetration. Further refinement of this technology may lead to the development of an optical surrogate for biopsy.

Introduction Inflammatory breast cancer (IBC) is an aggressive and rare cancer with a poor prognosis and a need for novel targeted therapeutic strategies. Preclinical IBC data demonstrates strong activation of the PI3K/mTOR and JAK/STAT pathways, expression of inflammatory cytokines and tumor associated macrophages (TAMs). Methods Archival tumor tissue from three disease types (IBC treated with neoadjuvant chemotherapy (NAC) (n=45); invasive ductal carcinoma (IDC) treated with NAC (n=24; ‘treated IDC’); and untreated IDC (n=27; ‘untreated IDC’)) was analyzed for the expression of biomarkers pS6 (mTOR), pJAK2, pSTAT3, IL6, CD68 (monocytes, macrophages) and CD163 (TAMs). Surrounding non-tumor tissue was also analyzed. Results Biomarker levels and surrogate activity by site-specific phosphorylation were demonstrated in the tumor tissue of all three disease types but were highest in IBC and treated IDC and lowest in untreated IDC for pS6, pJAK2, pSTAT3 and IL6. Of 37 IBC patients with complete biomarker data available, 100% were pS6 positive and 95% were pJAK2 positive. In non-tumor tissue, biomarker levels were observed in all groups but were generally highest in untreated IDC and lowest in IBC, except for JAK2. Conclusions IBC and treated IDC display similar levels of mTOR and JAK2 biomarker activation, suggesting a potential mechanism of resistance after NAC. Biomarker levels in surrounding non-tumor tissue suggest that the stroma may be activated by chemotherapy and resembles the oncogenic tumor-promoting environment. Activation of both pS6 and pJAK2 in IBC may support dual targeting of mTOR and JAK/STAT pathways, and the need for prospective studies to investigate combinatorial targeted therapies in IBC.

The case definition for inflammatory breast cancer (IBC) is controversial. The American Joint Committee on Cancer defines IBC as redness, warmth and edema involving at least half the breast. The SEER program relies on a pathologic finding of dermal lymphatic invasion and recently added those with clinical involvement of more than 3/4 of the breast. We established a registry to collect information and specimens from IBC patients to clarify the epidemiology and biology of these tumors. The goals of this report are to suggest improvements regarding case definitions and provide data on the variety of presentations relevant to early diagnosis.

Response to standard IBC chemotherapy is a dominant prognostic factor in determining patient outcomes. In our study, with limited statistical power, delay in diagnosis defined as >60 days from the time of first physician contact did not seem to affect patient outcomes. Data support similarities between classic and "atypical" IBC.