Mesothelin: A Potential Therapeutic Target in Triple-Negative Breast Cancer

A prognostic disease marker that often occurs in patients with triple-negative breast cancer may lead to development of a medication to close a therapeutic gap in targeted cancer treatment.

In a September 6, 2014 online release from the journal Breast Cancer Research and Treatment, researchers Li et al reported a relationship between the presence of a prognostic marker known as mesothelin and worse outcomes in patients with breast cancer.

Like other biomarkers that have been identified and later exploited as treatment targets, anti-mesothelin agents may be a therapeutic target in breast cancer.

Clinical data from 141 patients with breast cancer at a single center were analyzed for a relationship between mesothelin levels and therapeutic outcomes. The researchers compared expression of mesothelin using an immunohistochemistry or RNA transcript level, and identified significant associations between high mesothelin levels and several negative outcomes in affected patients.

High mesothelin levels were associated with a 30% increase in the risk of having a large tumor burden, a 234% increase in the risk of having at least 1 affected axillary lymph node, a 103% increase in inferior disease-specific survival, and a 206% reduction in overall survival—independently of the number of axillary lymph nodes with cancer and tumor size.

To confirm this data, researchers analyzed the same relationship in 844 patients who participated in The Cancer Genome Atlas (TCGA) project, and successfully replicated the results of the initial trial.

Breast cancers that do not have progesterone, estrogen, or HER2 receptors—so called "triple-negative breast cancers"—are also more likely to have the mesothelin prognostic indicator.

Progesterone, estrogen, and HER2 receptors are important targets of current breast cancer therapies, and a lack of treatment targets in triple-negative breast cancer contributes to the inferior outcomes in patients. If an effective agent is used to target mesothelin, such an agent would close a major therapeutic gap in breast cancer treatment.

Reference:

Li YR, Xian RR, Ziober A, et al. Mesothelin expression is associated with poor outcomes in breast cancer [published online September 6, 2014]. Breast Cancer Res Treat. 2014.