An NCI-designated Comprehensive Cancer Center
By City of Hope | November 9, 2018

Chelbowski Bio Image Rowan Chlebowski, M.D., Ph.D.
Rowan Chlebowski is of two minds.
On the one hand, he’s a medical oncologist and breast cancer expert. On the other, he’s a scientist specializing in observational studies who ranks among the most cited researchers in the world.
“You can see, I’m trying to go in the middle a little bit,” said Chlebowski, M.D., Ph.D., who joined City of Hope in 2017 as research professor in the Department of Medical Oncology & Research Therapeutics.
He already has published studies that helped rewrite guidelines for treating complications of menopause — and played a role in reducing the number of women confronted by breast cancer.
In a more recent headline-grabbing study, he and his colleagues found that cutting fat intake modestly could provide breast cancer patients with a better chance of survival. This line of inquiry one day may go beyond dietary advice and produce new therapies for breast cancer.

Dramatic Results

Chlebowski works with the Women’s Health Initiative (WHI), a large-scale, long-term effort funded by the National Institutes of Health that combines clinical trials with an observational study.
Thanks to his important results from the WHI, Chlebowski has earned a spot among the "World’s Most Influential Scientific Minds." That list, created by Thomson Reuter and currently maintained by Clarivate Analytics, tracks the researchers with a high number of studies that rank in the top 1 percent for most citations over the course of 11 years.
The news-making May 2018 JAMA Oncology report derives from an arm of the WHI. The study, begun in 1993, randomly divided nearly 49,000 postmenopausal women into two groups. Some joined an eight- and-a-half-year program encouraging a low-fat diet with more fruits, vegetables and grains. The rest maintained their usual eating habits.
More than 17 years later, Chlebowski and his colleagues went back and analyzed longitudinal data about the more than 1,700 participants who were diagnosed with breast cancer. What the scientists found: The low-fat diet reduced the risk of dying from cancer by 22 percent — rivaling the benefits of some mainline therapies.

Don’t Call It a ‘Lifestyle Change’

Chlebowski believes that his results support a simple, practical (and familiar) message: everything in moderation.
The fact is, the WHI intervention was not a drastic one. Although the figure has risen slightly, back then fat accounted for about 30 percent of caloric intake in an average diet; the low-fat diet in the study aimed to bring that down to 20 percent.
In practice, the reduction was smaller than that. The average participant took in about 24 percent of calories from fat and lost about five pounds in the first year, regaining later.
“Just a little bit of change can make a difference,” Chlebowski said.
Terminology may be a problem. Taking on a “lifestyle change” can sound too intimidating. According to Chlebowski, the WHI diet is doable and sustainable. He pointed to one passage in particular from his 2017 Journal of Clinical Oncology paper based on the same WHI arm: “A modest reduction in fat intake with minimal weight loss represent an easily achievable goal for many.”
“That sounds almost like a public health message, if you ask me,” he said with a smile.

Seeking a Target

The JAMA Oncology study also points to a way forward that unites Chlebowski’s interests in breast oncology and observational research.
His analysis showed that women with abdominal obesity benefited most from the low-fat diet, as did those who were on the program longest after their breast cancer diagnosis.
Here, Chlebowski sees an enticing clue about the relationship between breast cancer and metabolic syndrome, a condition that includes a combination of high blood pressure, blood sugar and cholesterol, as well as excessive belly fat. Metabolic syndrome increases the risk for breast cancer.
Chlebowski’s hypothesis holds that the tumor manipulates its environment, tricking the immune system into an inflammatory response that abets the disease. He thinks the low-fat diet promoted survival because it interfered with the molecular mechanism involved with metabolic syndrome — and behind cancer’s ruse.
“Once a tumor gets there and initiates the host response, you have a target that the dietary intervention can hit,” he said. “That’s a new concept. Why would it work afterward instead of before? Because the tumor creates a new environment.”
Collaborating with a colleague at UCLA-Harbor Medical Center, he is examining the WHI data from new angles, steering the endeavor toward precision medicine. Soon, that work could help doctors individualize the dietary advice they offer their patients.
“You might be able to say to some people, ‘What you’re doing is fine. You don’t need to change,’” Chlebowski said.
On a longer timescale, his research may even identify a previously unknown weak spot that medical oncologists can use to beat back breast cancer.
“The ultimate correlate will be to look at a lot of biological factors,” he said. “If you can find the immediate mediator, you may be able to come up with a targeted pharmacological intervention.”

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