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Breast Cancer Linked to Inflammation
12/20/2010
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by Craig Weatherby


A study in mice virtually proves that inflammation is essential to creation of breast cancer.
 
The study involved mice genetically engineered to develop breast cancer, but in which researchers could block a key gene switch needed to trigger inflammation.
 
Key Points
  • Mouse experiment proves that local inflammation drives creation of breast cancer.
  • Study used bio-engineered mice to pinpoint the inflammation-triggering gene “switch” responsible for cancer-promotion.
  • Omega-3s and food-borne polyphenolssuch as in tea, berries, spices, olives, and cocoatend to suppress over-activation of this trigger.
  • See the related story in this issue, Omega-3s Curb Breast Cancer in Cells.
The study targeted a particular gene “switch” called Nf-kappa B or NFKB, and its results prove that over-activation of NFKB is essential to formation of breast cancer… at least in mice, and very likely in women, too.
 
The landmark results showed that tumors would not develop when the inflammation-triggering NFKB switch was blocked selectively in the animals’ breast tissues (Liu M et al. 2010).
 
As a consequence, scientists from the Kimmel Cancer Center at Virginia’s Thomas Jefferson University say they’ve “definitively” shown that inflammation in the breast  promotes growth of cancer stem cells responsible for tumor development.
 
Critically, the Kimmel team found that inactivating inflammation selectively within the breast reduced activity of these cancer stem cells, and stopped breast tumors from forming.
 
The study was funded by support from the National Institutes of Health, the Dr. Ralph and Marian C. Falk Medical Research Trust, and a grant from the Pennsylvania Department of Health.
 
“These studies show for the first time that inactivating the NFKB inflammatory pathway in the breast epithelium blocks the onset and progression of breast cancer in living animals,” said Richard G. Pestell, M.D., Ph.D., Director of the Kimmel Cancer Center and Chairman of Cancer Biology (TJU 2010).
 
Study co-author Michael Lisanti added the key point, saying, “This finding has clinical implications. Suppressing the whole body’s inflammatory process has side effects. These studies provide the rationale for more selective anti-inflammatory therapy directed just to the breast” (TJU 2010).
 
However, NFKB is necessary to human health, so the trick is to either block its activation only in breast tissues… or only in the specific, as yet unclear physiological contexts that cause the over-activation of NFKB now shown essential to cancer formation.
 
Findings encourage testing of anti-inflammatory diets and drugs
Although inflammation mediated by NFKB has long been thought to be important in breast cancer development, the theory had been un-testable because NFKB is essential to embryo development.
 
As Dr. Pestell said, “When you try to knock out NFKB genes in mice, they die” (TJU 2010).
 
He solved this problem by bio-engineering mice in which the inflammatory system within the adult animal’s normal breast could be regulated… which allowed selective inactivation of NFKB in different cell types.
 
They then demonstrated that this inactivation also reduced the number of cancer stem cells in the breast.
 
“That told us that inflammation, through the action of NFKB, is important to the growth and activity of cancer stem cells,” Dr. Pestell said (TJU 2010).
 
Because this research relied on genetic modifications, it obviously cannot be replicated in women.
 
But common food factors are known to moderate the pro-inflammatory NFKB gene switch identified in the study.
 
So it should be possible through testing to find the nutrients and food factors that block NFKB selectively enough to help prevent breast cancer while keeping women’s immune systems healthy.
 
Many of the polyphenols in plant foods are proven to suppress over-activation of NFKB, as are the omega-3s in fish fat (see our companion report on a related study, “Breast Cancer Formation Linked to Inflammation”).
 
And unlike any drugs discovered to date, moderate intake of food-borne polyphenols appears to only suppress NFKB when it is activated inappropriately … not when the inflammation it triggers is needed to fight an infection or address a wound.
 
 
NFKB: Needed, but dangerous when over-activated
NFKB is one of several families of proteins called nuclear transcription factors, which prompt cells to express certain genes. (For simplicity’s sake, we’ll follow standard practice and refer to the NFKB group as though it were one compound.)
 
In the case of NFKB, the genes it causes to be expressed stimulate immune-system cells to mount an inflammation response.
 
And as the author of a review article put it, chronic activation of NFKB, in the absence of real threat requiring an inflammation response, is dangerous to health: “…pathological dysregulation of NFKB is linked to inflammatory and autoimmune diseases as well as cancer” (Hooper C 2010).
 
Study pinpoints a particular NFKB pathway
There are two NFKB cell-signaling pathways, known as the “canonical” pathway and “non-canonical” routes.
 
The canonical pathway stimulates inflammation, while the non-canonical pathway enables the production of immune system cells called lymphocytes.
 
Dr. Pestell and his colleagues show that activation of the “canonical” NFKB pathway promotes breast cancer development.
 
The inflammatory cascade in the breast starts when the infamous HER2 gene activates NFKB, which stimulates pro-inflammatory immune cells (macrophages) that in turn produce tumor growth-promoting factors.
 
Researchers who contributed to the study included scientists from the National Cancer Institute, the Nigata University of Pharmacy and Applied Life Sciences in Japan, the University of Western Australia, and the Lombardi Comprehensive Cancer Center at Georgetown University Medical School.
 
 
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