Obesity and breast cancer – new links

Of course, doctors and biologists are trying to calculate all the factors that increase the likelihood of this tumor. One of these risk factors is called overweight. Obesity is generally considered to be closely related to cancer, but it is a breast tumor that occurs when overweight is especially common. Two years ago, an article appeared in the journal Science, the authors of which claimed that the problem was in a cholesterol derivative, 27-hydroxycholesterol, which acts on cells like estrogen (and it is known about estrogen that in 75% of cases it stimulates the growth of tumors). The more cholesterol, the more of its oncogenic derivative, and with obesity in the body, obviously, there will be an excess of cholesterol. 

Researchers from Cornell University describe another mechanism linking obesity with breast cancer (Stiffer breast tissue in these women promotes tumors). According to Claudia Fischbach and her colleagues, the structure of adipose tissue itself and its mechanical characteristics can play a significant role in the malignant degeneration of cells. The initial idea was to test how genetic obesity and acquired obesity, which arose due to an unreasonable diet, work. When we compared mice that were overweight due to a genetic predisposition with mice that were obese due to over-feeding, it turned out that in both cases, adipose tissue has a characteristic feature - it is quite rigid.

The filaments of intercellular matter that hold cells together in breast tissue become less elastic than usual with obesity. Such rigidity, as the authors of the work in Science Translational Medicine write, provokes the release of inflammatory molecules by cells that find themselves in "harsh conditions". And the fact that chronic inflammation is often followed by cancer has been known for a long time (we recently wrote about one of the mechanisms linking one with the other). And indeed, when human cells, in which signs of malignant degeneration had already begun to manifest themselves, were placed in a network of intercellular filaments taken from "obese" mouse tissues, such cells were more likely to turn into real tumor cells. 

Reducing body weight makes adipose tissue less rigid, so perhaps losing weight can reduce the likelihood of breast cancer, but additional clinical studies are needed here for unambiguous conclusions. It is known that areas of increased density that are visible during mammography usually indicate a possible focus of the disease, but they are often not visible because of the same adipose tissue. That is, if you are overweight, you need a more thorough diagnosis for malignant threats. 

However, unfortunately, cancer tends to return after treatment: some cells remain alive after surgery and subsequent therapy and can give rise to a new tumor, either in the same place as before, or in another. Researchers from the British Cancer Institute have developed a diagnostic test that allows you to determine the presence of such traces of cancer in the body long before new clinical symptoms appear. The peculiarity of the method is that there is enough blood sample: DNA from malignant or "almost-malignant" cells, which floats through the bloodstream, is checked for the presence of mutations characteristic of breast cancer. Blood is taken for analysis several times at certain intervals, and by the accumulation of mutations, it is possible to assess how high the risk of the disease returning is. 

The experiment involved 55 patients whose tumor was removed at an early stage. In women who had cancer DNA detected in their blood, the risk of tumor recurrence increased 12-fold, and such a prognosis could be made almost 8 months before the clinical manifestation of cancer. The DNA found in the blood was compared with the characteristics of the primary tumor, which was previously disposed of with surgery and chemotherapy. The full results of the research are published in Science Translational Medicine (Seo et al., Obesity-dependent changes in interstitial ECM mechanics promote breast tumorigenesis). 

That is, on the one hand, this method works with each individual case, on the other hand, it allows you to catch a variety of breast cancers, because, according to the authors of the work, mutations peculiar to most types of tumors are tracked here. The main thing is the dynamics of the accumulation of mutations: it can be used to tell whether the surviving cancer cells are developing, multiplying their own number, or simply quietly dying somewhere in the bowels of the body. And, in which case, a preventive chemotherapeutic blow can be applied to prevent the formation of a repeated tumor. Whether this method of diagnosis can be adapted to other oncological diseases, time will tell. 

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03.09.2015