What is triple negative breast cancer? Here's What New Study Shows on the Evolution of This Aggressive Subtype of Cancer

 

Basal-like breast cancer, also known as triple-negative cancer, is a particularly aggressive subtype of breast cancer with limited treatment options. Although the luminal (cells that line the surface of the mammary duct) and basal subtypes of breast cancer are unknown, studies suggest that basal-like cancers may arise from luminal epithelial cells.

Basal-like breast cancer, also known as triple-negative cancer, is a particularly aggressive subtype of breast cancer with limited treatment options. Although the luminal (cells that line the surface of the mammary duct) and basal subtypes of breast cancer are unknown, studies suggest that basal-like cancers may arise from luminal epithelial cells.

What is triple-negative breast cancer?

According to the American Cancer Society, triple-negative breast cancer (TNBC) accounts for about 10–15 percent of all breast cancers. The term triple-negative breast cancer refers to the fact that the cancer cells do not have estrogen or progesterone receptors (ER or PR) and make none or too much of a protein called HER2. (The cells test "negative" on all 3 tests.) TNBC differs from other types of aggressive breast cancer in that it grows and spreads quickly, has fewer treatment options, and has a poor prognosis (outcome). .

TNBC is considered an aggressive cancer because it grows quickly and is more likely to spread once it is found. It is also more likely to come back after treatment than other types of breast cancer.

Here's What the Study Shows

In a new study, researchers from the Boston University Chobanian and Avedisian School of Medicine demonstrate that proper control of a cellular pathway known as the Hippo pathway inhibits the growth of triple-negative breast cancer.

These findings appear online in the journal Nature Communications.

"We found that when this pathway is dysregulated or impaired, luminal epithelial cells in the mammary gland rapidly transition to a basal-like state and develop into triple negative carcinoma," said corresponding author Bob Verelas, PhD, associate professor of biochemistry explained.

In an experimental model, the researchers conditionally deleted the LATS1 and LATS2 genes, two components of the Hippo pathway, in the luminal epithelium of mammary glands. When these genes were deleted, the models rapidly developed basal-like breast carcinomas that closely resemble human basal-like breast cancers. They found that the development of these carcinomas depended on the activity of the Hippo pathway effector proteins YAP and TAZ, and that deletion of these two proteins reversed carcinoma development in their model.

According to the researchers, the gene-expression signature identified from Lats1/2-deleted tumors can be used to identify aggressive features associated with triple negative breast cancer. Because basal-like breast cancer is notoriously difficult to treat, Varelas hopes these findings can be leveraged to help guide new directions for better treatments and improved patient outcomes. "A better understanding of the cellular mechanisms leading to the development of these cancers is essential for identifying new therapeutic options," he said.