A new study has linked deficiency in a gene that controls autophagy – a process that recycles cell waste – with triple-negative breast cancer. The researchers suggest increasing activity of the gene could be an effective way to treat patients with this most aggressive and stubborn cancer.
Reporting in the journal EBioMedicine, the University of Texas (UT) Southwestern Medical Center team describes how it found a strong link between the autophagy gene beclin 1 and the most aggressive type of breast cancer.
Beth Levine, a UT professor and director of the Center for Autophagy Research, and colleagues analyzed data from over 3,000 patients in two large breast cancer databases: the Cancer Genome Atlas (TCGA) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC).
They found that reduced activity of beclin 1 was linked to both a higher rate of triple-negative breast cancer and a poorer prognosis for breast cancer patients.
The team believes this is the first study to report a link between beclin 1 and triple-negative breast cancer in humans, and confirms similar findings from mouse studies.
Prof. Levine, who is also a Howard Hughes Medical Institute investigator at UT Southwestern, says their findings suggest decreased beclin 1 activity contributes to breast cancer and poor survival outcomes:
“With low beclin 1 expression, you have up to a 35-fold higher risk of having triple-negative breast cancer. That’s really strong.”
Triple-negative breast cancer is when the cancer cells are low in three types of receptor: estrogen, progesterone and human growth factor receptor 2 (HER2). A receptor is a protein that responds to particular chemical signals.
Triple-negative breast cancer accounts for around 10-20% of breast cancers. Unfortunately, this most aggressive cancer often resists chemotherapy, the standard treatment.
Prof. Levine says the study identifies a potential new pathway to target, and notes “therapies that increase beclin 1 activity in breast cancer may be beneficial.”
For the study, the team analyzed 3,057 breast cancer cases for levels of expression of beclin 1 and BRCA1, a nearby gene that is associated with inherited breast cancer.
They already knew around 35% of all breast cancers are missing copies of both these genes, and they wanted to find out which one was more important. Prof. Levine explains:
“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.”
Not only did they establish that low expression of beclin 1 is linked to a 35-fold higher risk of triple-negative breast cancer, they found it is also linked to worse outcomes. Breast cancer patients with low beclin 1 expression levels had a 67% higher risk of dying, compared with patients with high levels.
The team concludes that increasing expression of beclin 1 could be a promising therapy for breast cancer, especially for patients with the triple-negative type.
Beclin 1 is already a target of four classes of drug approved to treat other types of cancer, and the team suggests more research should now be done to see whether these could also save lives of breast cancer patients.
Funding for the research came from the National Institutes of Health and the Cancer Prevention and Research Institute of Texas. Prof. Levine has also worked as a paid consultant to Novus Biologicals, who market an antibody for beclin 1 that is used as a marker in research.
Problems with cell recycling and clean-up processes are also thought to be factors in other diseases, such as Amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease.
For example, in October 2014, Medical News Today learned how increased protein instability may lead to ALS. The researchers found mutations in a gene resulted in misfolded, useless proteins that accumulate in brain cells faster than the clean-up process can clear them away.