At University of Texas Southwestern Medical Center, Dr. Beth Levine, director of the Center for Autophagy Research, is exploring a connection between aggressive breast cancer and a gene involved in regulating autophagy, a natural cell process of recycling unneeded components. She, along with the rest of her research team, recently published an article in EBioMedicine that described the connection.
“We have potentially identified a new pathway to be targeted in the most aggressive, difficult-to-treat form of breast cancer,” said Dr. Levine, in a news release. “These data suggest that decreased beclin 1 activity contributes to breast cancer and poor survival outcomes. As a result, therapies that increase beclin 1 activity in breast cancer may be beneficial.”
In “Decreased BECN1 mRNA Expression in Human Breast Cancer is Associated With Estrogen Receptor-Negative Subtypes and Poor Prognosis,” the research team used two breast cancer databases (The Cancer Genome Atlas and Molecular Taxonomy of Breast Cancer International Consortium) to study mRNA expression of 3,057 patients with triple-negative breast cancer, which is considered an aggressive cancer that is difficult to treat with chemotherapy. Results showed a high correlation between beclin 1 and triple-negative breast cancer.
“With low beclin 1 expression, you have up to a 35-fold higher risk of having triple-negative breast cancer. That’s really strong,” said Dr. Levine.
The team was interested in beclin 1, as well as BRCA1, as the genes are associated with inherited breast cancer and are near the 17q21 breast cancer tumor susceptibility locus. “We know that about 35 percent of all breast cancers are missing copies of both the beclin 1 and BRCA1 genes,” said Dr. Levine. “To find out which of the two genes is important, we looked at the levels of expressions of both genes and how they related to different clinical features of breast cancer. Strong associations were seen between low expression of beclin 1, but not BRCA1, and adverse clinical features.”
Although BRCA1 is one of the most well-known tumor suppressors associated with breast cancer, in the case of triple-negative breast cancer, beclin 1 could be of interest in developing new therapies. Currently, four drug classes are capable of increasing beclin 1 activity and are already approved to treat other types of cancer: inhibitors of either beclin 1/BCL-2 binding, protein kinase B (AKT), epidermal growth factor receptor (EGFR), or HER2. Clinical trials would be required to investigate any in the context of triple-negative breast cancer.