Researchers from UT Southwestern Medical Center revealed an important association between the most aggressive type of breast cancer, triple-negative breast cancer, and the gene beclin 1 that regulates the normal cellular recycling process, called autophagy.
The study, entitled “Decreased BECN1 mRNA Expression in Human Breast Cancer is Associated With Estrogen Receptor-Negative Subtypes and Poor Prognosis” was published in EbioMedicine by Hao Tang and Salwa Sebti, co-first authors of the study and led by co-senior authors Dr. YangXie and Dr. Beth Levine from the Department of Clinical Sciences and Center for Autophagy Research, at the University of Texas Southwestern Medical Center.
Triple-negative breast cancer corresponds to 10 to 20% of all breast cancer cases. The disease is characterized by cancer cells without receptors for estrogen and progesterone and low expression levels of the human protein growth factor receptor 2 (HER2). In this type of cancer, chemotherapy is the standard of care, however, it seldom has high levels of effectiveness.
In this study, the research team analyzed 3,057 breast cancer patients from the Cancer Genome Project (US) and the Molecular Taxonomy of Breast Cancer International Symposium in the United Kingdom and Canada. Researchers measured the expression levels of beclin 1 and BRCA1, a gene that is linked with inherited breast cancer, observing that elevated occurrence of triple-negative breast cancer and poor prognosis for breast cancer patients were associated with low expression/activity of the beclin 1 gene.
In a news release, Dr. Levine said that the team identified a potential new pathway that may be manipulated to treat the most aggressive and very hard to treat form of breast cancer. “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,” added Dr. Levine.
Dr. Levine and Dr. Xie said that individuals with low beclin 1 expression will have 35-fold higher probability of developing triple-negative breast cancer. Furthermore, approximately 35% of all breast cancers do not have copies of the genes beclin 1 and BRCA1. Dr. Levine added that they found important correlations between low expression of beclin 1 and clinical features of breast cancer, but not with BRCA1.
Dr. Xie said the probability of death in patients with breast cancer and low beclin 1 expression could increase to 67% when compared with patients with higher levels of beclin 1 expression.
A new treatment for patients with breast cancer, especially those with triple-negative disease, could target the increase of beclin 1 activity. In other types of cancers, several approved drugs that increase beclin 1 activity have been used. Among them are four classes of drugs: inhibitors of either beclin 1/BCL-2 binding, protein kinase B (AKT), epidermal growth factor receptor (EGFR), or HER2.
Dr. Levine said that these findings will need further research and additional drugs that can upregulate beclin 1 and possibly help save more breast cancer patients’ lives.
The work was financially supported by the National Institutes of Health and the Cancer Prevention and Research Institute of Texas.