Obesity Promotes TNBC by Metabolically Activating the Macrophages in Mammary Fat

Obesity is now competing with smoking on the grounds of increasing the risk of cancer in the United States. The recent study from the researchers at Chicago finds out that women already suffering from breast cancer are at a greater risk of developing metastatic and advanced breast cancer from obesity, that is the most well known and common type of cancer among women.

Breast cancer develops in fats, also known as adipose tissues. The Triple-negative breast cancer (TNBC) is difficult to treat due to the fact that its cells do not contain the most common three drug targets that are the human epidermal growth factor receptor 2, the estrogen receptor, and the progesterone receptor.

The research paper “Metabolically activated adipose tissue macrophages link obesity to triple-negative breast cancer” got published in the Journal of Experimental Medicine on 3rd May 2019.

“These cancers can be particularly aggressive,” said lead author Lev Becker, Ph.D., a lecturer in the Ben May Department for Cancer Research at the University of Chicago. “For patients with TNBC, there are few therapeutic options. The survival rate is quite low. And cancer tends to be dramatically elevated in patients who are overweight or obese.”

As Becker in his study mentioned obesity as “a global epidemic”, the United States is placed at 12th position in the world. Obesity attacks 36% of people aging between 20 to 39, 41% for people aging 60 and above and 43% for people aging from 40 to 59.

“Current treatment of breast cancer patients ignores the ongoing obesity epidemic,” said study co-author Marsha Rosner, Ph.D., the Charles B. Huggins lecturer in the Ben May Department for Cancer Research. “In order to take this into consideration, we need to help patients lose weight or identify new drug targets that would be effective in obese cancer patients.”

Once cancer has been diagnosed, there is not enough time for you to lose weight before starting the treatment. Therefore, Rosner said his bottom line is to “promote weight loss as a cancer prevention measure, incorporate weight loss as a component of therapy for patients with breast cancer, and develop specific drug targets that could be leveraged to address the obesity component of the disease.”

Becker, Rosner and other team members revealed the biology behind the mechanism of development of TNBC due to obesity. Their research shows that obesity recodes the macrophages into pro-inflammatory and metabolically activated macrophages. Macrophages are the scavengers which attack foreign particles like bacteria viruses or tumor cells.

Becker further explained, “Our studies, in mice and humans implicate these metabolically-activated adipose tissue macrophages.” The metabolically activated macrophages settle themselves in mammary adipose tissues and release a type of inflammatory cytokine, interleukin 6 which can trigger tumorigenesis. These inflammatory cytokines mainly flourish on obesity.

What interleukin actually do is that it binds to the receptor of the already existing cancer cells fueling the process of cancer development. Becker explains this can stimulate “an even more aggressive stem cell phenotype. These cancer stem cells are able to encourage tumor growth and metastasis, enabling them to travel to other sites.”

Cancer patients who are at an advanced or metastatic stage have a high concentration of interleukin 6 in their blood which decreases their survival rate up to a great level.

The study authors describe obesity as a morbid condition that “facilitates tumorigenesis by creating tumor permissive conditions in multiple tissues.” This shows that the condition of chronic inflammation and tumorigenesis may overcome by anti-inflammatory therapies and weight loss.

In the study, when the researchers made obese mice have a low-fat healthy diet, they observed a reverse condition of inflamed macrophages and TNBC tumor formation in mammary fat. However, all over body weight remained elevated.

This recent research not only brings out the importance of weight loss as a preventive measure but also as a part of a treatment plan for breast cancer.

Emma Colleen

Emma’s professional life has been mostly in hospital management, while studying international business in college. Of course, she now covers topics for us in health.

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