Study Uncovers Hidden Risk for Breast Cancer in Some Women

Doctor comforting patient

Tests to look for metabolic obesity in patients eventually could become a part of regular wellness checkups and health screenings.

Update: On January 26, 2018, Neil Iyengar, Andrew Dannenberg, and colleagues presented a related study at the American Association for Cancer Research’s Obesity and Cancer conference. That research found actual measurement of body fat using a type of scan called dual-energy x-ray absorptiometry was a better predictor of breast cancer risk than body mass index (BMI). Specifically, they discovered high body fat levels were associated with an increased risk of estrogen-receptor positive breast cancer in post-menopausal women who had a normal BMI. The study was the largest of its kind and included nearly 3,500 women. The results of this study were published in JAMA Oncology on December 6, 2018.

The connection between obesity and some kinds of cancer, including breast cancer, is well established. Not only is obesity a risk factor for developing the disease, it’s also a poor prognostic indicator for people who are diagnosed — those who are obese tend to have worse outcomes than those who are not.

A handful of recent studies have suggested that it’s possible to be physically lean but metabolically obese — meaning that certain conditions in your body may bring about the risks that come with obesity even if you have a normal body mass index (BMI). Now, a new study led by teams from Memorial Sloan Kettering and Weill Cornell Medicine indicates for the first time that this so-called metabolic obesity in normal-weight women can increase the likelihood that they will develop breast cancer.

“We call these women the walking wounded. They’re currently not recognized as being unhealthy,” says MSK breast medical oncologist and researcher Neil Iyengar, the first author of the study, published in the journal Cancer Prevention Research.

Andrew Dannenberg, senior author of the study and Associate Director of Cancer Prevention at the Meyer Cancer Center of Weill Cornell Medical College, adds, “Physicians currently cannot reliably detect which patients who have a normal BMI may have underlying metabolic obesity that could be putting them at risk for cancer.”

Linking Fat and Cancer

Drs. Iyengar and Dannenberg investigate the biological mechanisms by which obesity promotes cancer. Earlier studies from their group have looked at breast cancer and tongue cancer.

One of the things the team studies is inflammation in the fat tissue and how it may drive cancer. The condition can lead to the release of various substances including hormones and growth factors that stimulate the development of cancer cells. These factors also serve as fuel for the growth of existing cancer cells.

We call [women with metabolic obesity] the walking wounded. They're currently not recognized as being unhealthy.
Neil M. Iyengar physician-scientist

Several cancers have been linked to obesity, including uterine cancer, colorectal cancer, and prostate cancer, though breast cancer has one of the strongest connections. “The breast is an organ that could be particularly susceptible to fat tissue dysfunction because the tissue where breast cancer most commonly arises — the milk ducts — is surrounded by fat,” Dr. Iyengar notes.

“One observation that caught our attention in our initial studies was that there was a group of patients with breast cancer who were not considered obese by BMI, but who had the same biological changes in their tissues that we see in obese patients,” he adds.

He and his collaborators set out to determine how common this problem was.

A Surprising Discovery

The current study included 72 women with normal BMIs who were undergoing mastectomy at MSK. Most had breast cancer, but some were having preventive surgery. The women donated blood samples as well as their breast tissue, so the researchers could look for changes in their bodies at the time of surgery.

The investigators were surprised to find that 39% of these women had inflammation in the fat tissue of their breasts. They also had higher-than-normal levels of aromatase, the enzyme that makes estrogen, in their breast tissue. Increased levels of estrogen in the breast could directly stimulate the development of breast cancer, Dr. Iyengar says.

“Interestingly, when we looked at the blood, we found that these women with fat inflammation and elevated aromatase had insulin resistance, which can be thought of as a precursor to diabetes. They also had higher triglyceride levels and other inflammatory changes,” he adds. “These are the kinds of changes we normally see in obese patients.”

Researchers are looking for better ways to diagnose metabolic obesity.

These findings suggest that the obesity epidemic is much greater than currently recognized and includes some women of normal weight. The investigators believe that a link is also likely to exist between metabolic obesity and cancer in men.

Developing a New Method of Diagnosis

So now the question is, how would a woman know if she falls into this category?

Currently, the only way to detect inflammation in fat tissue is by looking at tissue that comes from a biopsy or surgery, Dr. Iyengar explains, procedures that are invasive and not typically employed on a regular basis.

His team is currently undertaking new studies to look for other ways to diagnose metabolic obesity. These methods may include scans that could measure a person’s body composition or blood tests that could be conducted during a routine physical. He says these tests eventually could become a part of regular wellness checkups and health screenings, and not just for those with cancer.

The researchers feel a sense of urgency about developing these new tests. “Right now these patients go to the doctor, who looks at their normal BMI and says, ‘Keep up the good work,’” Dr. Dannenberg says. “But in fact they may have undetected metabolic obesity that could put them at risk not only for cancer but also for diabetes, high blood pressure, heart disease, and other kinds of diseases.”

Dr. Iyengar adds that a lack of physical activity or eating an unhealthy diet may contribute, but it’s too early to know for sure. “This is an active area of research and is reshaping the way we think about who is healthy and who is not,” he says.

“Once we can more easily and reliably detect who has metabolic obesity, our goal is to ultimately develop interventions — such as specific diets, exercise programs, or even medications — that are tailored to decrease the risk of cancer and other disorders related to obesity,” he concludes.

This work was supported by the National Institutes of Health under grants NIH/NCIHHSN2612012000181, CA210184-01, CA185293, and P30 CA008748. It was also supported by the Prevent Cancer Foundation, the Conquer Cancer Foundation of the American Society of Clinical Oncology, the Breast Cancer Research Foundation, the Botwinick-Wolfensohn Foundation, Myrna and Bernard Posner, the National Breast Cancer Foundation, and the Victorian Government Operational Infrastructure Support Program.