Key Genetic Driver Identified For A Rare Type of Triple-Negative Breast Cancer

Highlights

• Triple negative breast cancer is a most aggressive and rare form of breast cancer.
• Metaplastic breast cancer is a subtype of triple negative breast cancer.
• The role of breast cancer protein called CCN6 in breast cancer development, was studied by a research team from the University of Michigan.
• Understanding the disease may improve treatment options.

The role of a poorly understood breast cancer protein called CCN6 in breast cancer development was studied by a research team from the University of Michigan. The research study was published in the journal Oncogene.

The research team deleted CCN6 from the mammary gland in the mice and the model may help to study effects that are specific to the loss of protein. When checked in at different ages, the mammary glands were not developed properly and there was a delayed development.

Kleer, Harold A. Oberman Collegiate Professor of Pathology and director of the Breast Pathology Program, University of Michigan Comprehensive Cancer Center, said, "After a year, the mice started to form mammary gland tumors. These tumors looked identical to human metaplastic breast cancer, with the same characteristics. That was very exciting."

Metaplastic breast cancer is a rare and an aggressive type of triple-negative breast cancer. 20% of all breast cancers are triple negative while 1% is metaplastic.

Kleer, said, "Metaplastic breast cancers are challenging to diagnose and treat. In part, the difficulties stem from the lack of mouse models to study this disease."

"Our hypothesis, based on years of experiments in our lab, was that knocking out this gene would induce breast cancer. But we didn't know if knocking out CCN6 would be enough to unleash tumors, and if so, when, or what kind."

Advertisement

"Now we have a new mouse model, and a new way of studying metaplastic carcinomas, for which there's no other model."

Knocking down CCN6 induced process is known as the epithelial to mesenchymal transition.

Advertisement

Kleer, said,"This process is hard to see in tumors under a microscope. It's exciting that we see this in the mouse model as well as in patient samples and cell lines."

The research team looked at the tumors that were developed by the mice under a microscope and identified several genes which can be targeted. Some of the options like p38 were found to have antibodies or inhibitors against them.

Further research will be carried to test potential therapies along with existing chemotherapies. This will play a better understanding of the breast cancer and discover new genes.

The author also concluded that understanding the disease may help to treat it. "For patients with metaplastic breast cancer, it doesn't matter that it's rare. They want - and they deserve - better treatments."

Triple-Negative Breast Cancer
Triple-negative breast cancers are diagnosed based on the presence or absence of three receptors like estrogen receptors, progesterone receptors and human epidermal growth factor receptors 2.

References:

1. E E Martin, W Huang, T Anwar, C Arellano-Garcia, B Burman, J-L Guan, M E Gonzalez, C G Kleer. MMTV-cre;Ccn6 knockout mice develop tumors recapitulating human metaplastic breast carcinomas. Oncogene, 2016; DOI: 10.1038/onc.2016.381
2. Triple-Negative Breast Cancer - (http://www.breastcancer.org/symptoms/diagnosis/trip_neg)

Source-Medindia