Inflammatory Breast Cancer - Characterization

Characterization

Inflammatory breast cancer is a high grade aneuploid cancer, with mutations and overexpression of p53, high levels of E-cadherin and abnormal cadherin function. It is often regarded as a systemic cancer. A large number of IBC cases present as triple negative breast cancer (TNBC). Similar to TNBC as opposed to estrogen receptor-positive breast cancer, there is a high rate of relapses and metastases in the first 3 years after presentation but few late events (5 years or later).

It is characterised by the presence of cancer cells in the subdermal lymphatics on skin biopsy.

Searches for biomolecular characteristics produced a broad number of possible markers, such as loss of LIBC and WISP3 expression. Inflammatory breast cancer is in many ways very similar to late stage or metastatic breast cancer, however it can be distinguished from those cancer types both by molecular footprint and clinical presentation. On the molecular level some similarity exists with pancreatic cancer.

Estrogen and progesterone receptor status is frequently negative, corresponding with poor survival. The tumors are highly angiogenic and vascular, with high levels of VEGF and bFGF expression.

A number of proteins and signalling pathways show behaviour that can be considered paradoxical compared to their function in normal tissue and other breast cancer types.

• caveolin-1 and -2 are overexpressed and may contribute to tumour cell motility
• E-cadherin is overexpressed and paradoxically associated with especially aggressive type.

RhoC GTPase is overexpressed, possibly related to overexpression (hypomethylation) of caveolin-1 and -2. Caveolin is paradoxically tumour promoting. NF-κB pathway activation overexpression may contribute to the inflammatory phenotype.