Inflammation: The Missing Link

Noam VanderWalde, MD

On Saturday, the second day of the ASCO Annual Meeting, I went to the ASCO/AACR Joint Session on Inflammatory Cells and Cancer. At this session, Andrew Dannenberg, MD, of Weill Cornell Medical College, gave a fascinating lecture titled “Stromal Inflammation and Solid Tumors.”

Oncologists have long known that there is an association between certain lifestyles (ie, smoking, obesity, sedentary) and the likelihood of developing cancer, response to treatment of cancer, and survival after cancer. However, prior to this talk, I had never heard a potential mechanism for this association so elegantly explained.

Dr. Dannenberg’s underlying hypothesis is based on the data showing that chronic inflammation leads to increased rates of cancer. This certainly fits with the data showing increased rates of certain cancers in patients who have chronic inflammatory disease (ie, Crohn’s disease, ulcerative colitis, etc.). With that assumption, Dr. Dannenberg and his team sought to identify a connection between obesity and chronic inflammation in the breast. They started with mouse models and eventually moved on to human studies, which found that an increase in what they described as “crown-like structures of inflammatory cells” surrounding white adipose tissue correlated very strongly with increases in pro-inflammatory cytokines, including IL-6, IL-1B, and TNF-a. These pro-inflammatory cytokines also correlated strongly with an increase in aromatase. This is particularly interesting given the results of the IBCSG TEXT and SOFT trials presented at the ASCO plenary session, which showed a disease-free survival benefit with the use of an aromatase inhibitor over tamoxifen in premenopausal women who received ovarian suppression (known to cause weight gain).

One additional interesting fact demonstrated by the data is that although there was a strong correlation between these crown-like structures in the breast and obesity (with as many as 90% of obese women having them), there was still a large number of non-obese patients who had these structures (35% of the BMI < 25 group; 54% of the overweight (non-obese) group). Why some non-obese women have these structures that are associated with inflammation is unclear. Could it be due to sedentary lifestyle, age, or diet? Neil Iyengar, MD, the first author of the poster presentation of this data, admitted that all of these were potential explanations and that they are currently being looked into. He also explained that they are looking into possible systemic/blood markers that may be better predictors of inflammation than obesity.

The elegant experiments and studies performed by Dr. Dannenberg and his team are fascinating and are certainly a step forward in explaining the link between lifestyle and cancer. How this may impact our patients in the future is still to be determined. One personal concern is that many women who live healthy lifestyles may think that it is impossible for them to get cancer. Certainly, I have met many newly diagnosed breast cancer patients who eat healthy, exercise, and have no family history of cancer, and thus wonder how cancer happened to them. It is possible that systemic markers of inflammation may lead to different screening recommendations for those at “higher risk” for developing cancer, or may even become earlier screening methods themselves.

The current data should not make “healthier” women feel they are immune to developing cancer. I hope that women who eat healthy and exercise continue with recommended screening. Despite this minor concern, I am hopeful that as we learn more about the connection between lifestyle, inflammation, and cancer, we can better prevent and treat all cancers.