10. Characterizing the heterogeneity of triple-negative breast cancers using microdissected normal ductal epithelium and RNA-sequencing

Radovich, M., et al., 2013

Triple-negative breast cancer is defined by its properties that do not respond to traditional therapies: It is not estrogen or progesterone positive; it is not HER-2 positive. This means patients with triple-negative breast cancer have fewer treatment options than ER-positive, HER-2 positive patients. Triple-negative breast cancer patients have a poorer prognosis as well.

As you would expect, researchers are investigating both how triple-negative tumors form and how to develop treatments to target them. For this study, researchers used normal breast tissue from the Komen Tissue Bank to compare to triple-negative tissue to better understand this form of the disease.

Methods:

The scientists micro-dissected normal ductal epithelium (cells that line the ducts) from KTB normal tissue samples, from triple-negative cancer samples and from samples of tissue adjacent to tumors. They wanted to compare the three types to better understand heterogeneity in the triple-negative cancers. Heterogeneity describes the differences in cancer cells in the same tumor, or the differences in cancer cells among patients with the same type of cancer.

Findings:

Researchers found many differences among the micro-dissections. They noted the appearance of non-epithelial cells, such as immune cells and PD-1 (programmed death) associated with triple-negative tissue micro-dissections. They compared those micro-dissections directly with those of normal tissue to look at DNA mutations. They identified genes that were poorly regulated in triple-negative cells compared to normal.

Why this research is important:
While other studies have examined similar structural changes in triple-negative tumors, this one used micro-dissections and used normal tissue as a comparison. In particular, the use of KTB donor tissue allowed the scientists to observe heterogeneity in a whole new way, a way that may uncover biological insights to triple-negative breast cancer that will lead to better treatments.