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September 18, 2019 | 5 minute read

Under the Microscope: Dr. Andrew Dannenberg on “The Walking Wounded”

Postmenopausal

Normal BMI

Too much friggin’ trunk fat…

That’s my personal profile these days—one that qualifies me for “The Walking Wounded,” the large cohort of women that Dr. Andrew Dannenberg, Weill Cornell Medicine Professor of Medicine and Associate Director of Cancer Prevention at its Meyer Cancer Center, is worried about.

YouTube video

We may be walking around with a “hidden wound” that puts us at risk of cancer and cardiovascular disease: inflammation. “You can see it under the microscope,” he says. Cancer is often described as a wound that does not heal. Focusing solely on BMI may be giving us women a false sense of security when we might otherwise be trying to heal the wound, says Dannenberg, echoing the sentiments of many experts at AICR’s 2019 research conference on obesity and cancer.

Dannenberg and his colleagues recently published two studies analyzing data from the Women’s Health Initiative on postmenopausal women– one looking at breast cancer risk, another at cardiovascular disease.

Ask the Researcher:

Q: Tell us about your research on breast cancer in these women.

A: We looked at data from more than 3400 postmenopausal women and found that those who had a normal BMI– 25 or less– but who also had excess trunk fat, as defined by a scan called Dexa, had about a doubling in risk of estrogen receptor-positive breast cancer, the most common type of breast cancer.

Our study was the first to demonstrate that this condition—we also call it ‘MONW,’ metabolically-obese normal-weight, or ‘Skinny Fat’—is associated with an increased risk of breast cancer.

Q: What do you mean by “metabolically-obese”?

A: A variety of changes occurred within the blood of these women who had excess trunk fat but normal BMIs. For example, they had elevated inflammatory markers such as C-Reactive Protein and Interleukin-6, and they had higher than normal levels of insulin and leptin, which is evidence of abnormal metabolism. Based on their blood parameters, they looked like they’re metabolically obese.

Q: And what did you see under the microscope?

A: In an earlier study of normal BMI women, we saw inflammatory changes in the breast tissue of some women. Fat becomes inflamed. In the women who had inflamed breast fat, the fat cells were enlarged; they become sick or die and then blood cells called macrophages, which have the job of clearing the dead or injured fat cells, envelop the fat cells. We use the term ‘crown-like structure’ because the macrophages decorate the dead or dying adipocyte with a crown-like appearance.

Q: And you found similar results regarding cardiovascular disease in these women?

A: When we did the study on breast cancer, we noticed that some of the biomarkers for risk of cardiovascular disease were abnormal so that raised the possibility that the same women might be at increased risk of cardiovascular disease. The study we did– published recently in the European Heart Journal– demonstrated that postmenopausal women with normal BMIs who had excess trunk fat were at increased risk for cardiovascular disease.

Q: What’s happening to us women postmenopause?

A: After menopause, women tend to accumulate visceral fat—that is, fat around the abdominal organs—and visceral fat can trigger inflammation and insulin resistance. Loss of ovarian function can also impact appetite and metabolism. Estrogen itself stimulates metabolism, so it appears that the loss of estrogen contributes to the metabolic changes.

Q: Do men have a similar problem?

A: Certainly, men put on weight as they get older. That’s true. We don’t have any data yet for Skinny Fat men. It’s probably an issue.

Q: So, when my GP does my numbers and says my BMI is normal, should I pull up my shirt and show her what I call my “Ring Around the Belly?”

A: That’s exactly the issue. The take home message is that when a physician or health care provider tells you that you have a normal BMI, think twice. The problem is easily missed, and yet there can be severe consequences down the road– and it’s that period of time where you would have the opportunity to improve body composition and hopefully decrease your risk of developing disease. But I don’t trust visual inspection. I prefer an objective measurement. Many women will undergo bone density studies. The same instrument—if the computer software is there—can be used to assess body composition. And there are other ways of assessing body composition as well—such as bio impedance measurements.

Q: What’s next?

A: Fundamentally right now we’ve identified this new high-risk population—a very underrecognized medical problem of clear significance related to risk of cancer risk and cardiovascular disease. We need education, whether it’s health care training or lay education, to increase awareness.

We have a diagnostic; what we’re missing is a treatment. I think there needs to be laser-like focus on developing the treatment now because the problem undoubtedly accounts for a significant increase in disease burden over time.

Q: Any ideas for exploring treatments?

A: I think there are some practical research opportunities in the diet-exercise space. We hope to do a trial in conjunction with colleagues at MD Anderson to investigate whether a diet-exercise intervention in the Walking Wounded can improve body composition and blood biomarkers. I am also interested in exploring the effects of a whole food plant-based diet.

Aromatase inhibitors reduce the risk of estrogen-dependent breast cancer and might be beneficial in the Walking Wounded. However, it’s likely that a large number of women would need to be treated to prevent a single breast cancer. Furthermore, it’s unlikely that this type of agent would reduce the increased risk of cardiovascular disease that has been observed in this population.

I say in conclusion:

If you’re interested in prevention the way I am, having a new understanding of this risk is a great opportunity to have an impact, and that’s where research support from organizations like AICR is very important.

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