Exciting Advances in Inflammatory Breast Cancer at SABCS
Naoto Ueno, M.D., Ph.D., Department of Breast Medical Oncology
Inflammatory breast cancer (IBC) is one of the most aggressive subtypes of breast cancer. The MD Anderson Morgan Welch Inflammatory Breast Cancer Program and Clinic had a major presence at the San Antonio Breast Cancer Symposium with nearly 15 abstracts related to IBC. They included research on cytokine changes, mesenchymal stem cell interaction and several new targets.
So, what are the three most important issues in the field of IBC?
We need to differentiate the disease from non-IBC cancers at the molecular level, so oncologists can establish universal criteria for the diagnosis of IBC.
We need to find unique causes of IBC that can be developed as IBC-specific targets.
We need to uncover the risk factors associated with the development of IBC.
To address these issues it takes team medicine (multidisciplinary care) and team science. This applies internally at MD Anderson, but it's also critical to have a collaborative project at the international level.
Dr. Steven Van Laere from General Hospital Sint-Augustinus in Belgium and Dr. Francois Bertucci from the Institut Paoli-Calmettes, Centre de Recherche en Canc_rologie in France, have been working with our MD Anderson group for more than two years to integrate the gene expression dataset of IBC and non-IBC.
This is the largest dataset that has ever been created for IBC. Three Affymetrix gene expression data sets were combined, resulting in a series of 137 IBC and 252 non-IBC samples. We located four robust sample clusters, which may contribute to understanding the difference between IBC and non-IBC.
A total of 632 genes were differentially expressed and the analysis of this gene list identified an IBC-repressed network centered on TGF¤, which may be involved in metastasis. This is exciting because it may take us to the next level by developing novel targeted therapy or prognostic markers.
Another interesting finding came from Dr. Xiaoping Wang in my group. She found that tazarotene-induced gene 1 (TIG1) expression is significantly higher in IBC cell lines than in non-IBC cell lines. She confirmed that knocking down TIG1 expression in IBC cells reduced their proliferation, migration, and invasion in vitro.
Additionally, the silencing of TIG1 dramatically inhibited IBC tumor growth in a xenograft animal model. Most importantly, Dr. Wang identified Axl as a functional partner of TIG1 by showing that it interacted with, and stabilized, Axl in IBC cells. Axl is well known for regulating metastasis. Dr. Wang's results further identified TIG1 as an oncogenic gene that contributes to the tumorigenic and metastatic properties of IBC.
These discoveries are just a small part of our exciting progress that we see in IBC. It's a rare disease, but if you work as a team, rapid progress can be made.