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.


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.


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.