Diet Linked With Tumor Aggressiveness in Endometrial Cancer

Lindsay West, MD

The obese state of mouse models was shown to promote tumor aggressiveness in endometrial cancer, according to Lindsay West, MD.

In a preclinical study of mice with a diet switch, initial diet did not impact the final mouse or tumor weight. Mice that ate a high-fat diet throughout or were switched to a high-fat diet weighed more and had larger tumors than mice that were fed low-fat diets. According to these data, this highlights the importance of a low-fat diet as a means of improving endometrial cancer outcomes, West explained.

Mice were fed a controlled low-fat diet (n = 15) versus a high-fat diet (n = 15) starting at 3 weeks of age. Seven of the mice who were receiving a low-fat diet were switched to a high-fat diet, whereas 20 mice who received a high-fat diet were switched to a low-fat diet at 16 to 18 weeks.

Tumor weight was the greatest in the mice on a consistent high-fat diet (0.82 g), though this was not statistically different from the mice who were switched to the high-fat diet (0.48 g). Mice with the low-fat diet and those that were switched to the low-fat diet had tumor weights of 0.27 g and 0.32 g, respectively.

OncLive: Please provide an overview of this research.

What are the next steps following this research?

How does this research impact patients with endometrial cancer?

In an interview with OncLive, West, a gynecologic oncologist in the Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, discussed the relationship between low-fat or high-fat diets and endometrial cancer and how these can be investigated further.West: We presented work from Dr Victoria L. Bae-Jump’s lab where we fed mice various diets, either high in fat or low in fat, and then switched that diet. Those mice then developed endometrial cancer. We looked at the effect of diet on both normal tissue as well as endometrial cancer to determine whether there are differences and if switching the diet can reverse those changes.The next steps are to determine whether the mice had differing levels of estrogen since we know that obesity increases peripheral adiposity and ultimately influences estrogen levels. Sometimes, too much estrogen is thought to be the mechanism for endometrial cancer in many patients. We do not have that data yet, but we do have the blood from the mice that we plan to investigate to see if estrogen levels differ between the high-fat diet group and the low-fat diet group. We switched the diet of the mice before they developed endometrial cancer. This makes sense since the cancer cells had not developed their identity yet. We are not sure whether the diet influences that initial identity, but it may be interesting to see whether the mice develop cancer after their diet is switched.

What is the biggest unmet need for patients with endometrial cancer?

In a practical sense, it is hard to change your diet before there is a reason to do so. For many women, it is the diagnosis of endometrial cancer and understanding that there is a relationship between obesity and cancer that causes the inspiration for them to switch their diet. It would be interesting to see if we are able to induce endometrial cancer in these mice and then switch their diet. Do we see that same effect with lipid biosynthesis when it is upregulated because of a high-fat diet? Can we get that back down to an average level or even downregulate it by switching to a low-fat diet? That will be interesting and clinically applicable. Understanding how the quality of life interacts with prognosis, treatment, and survivorship is currently an unmet need. That is an important concept that is blowing up in our field. While that may be an unmet need now, it will not be for very long. We are realizing that even though progression-free survival and overall survival are such impactful outcomes, the quality of life is also important. Even if a patient lives for an extra 2 months, if they are in the hospital or feeling as if they cannot meaningfully interact with their family, that is just as important as those other endpoints.

Where do you see the treatment landscape headed in the future?

We are better understanding objective ways to measure quality of life so that we can integrate that into our research moving forward when we interact with patients in the clinic. Based on other fields, cancer treatment is no longer a one-size-fits-all strategy. For this field specifically, carboplatin and paclitaxel, was used for almost any advanced malignancy. We are seeing that even though we understand the molecular and genetic landscape of our cancers, we hopefully will still find targetable proteins or endpoints to better treat patients in a fashion that they may be more likely to respond to. This includes targeted treatments where they may have fewer side effects.

It would be enlightening if we could better understand the prognosis of endometrial cancer, so we can determine who to undertreat and overtreat. We are learning from clinical practice that heterogeneous types of cancer, such as endometrial cancer, have some patients who do better than others. We have not understood why for a long time, but that is something that has been coming to light recently and, hopefully, there is more to come with that in the future.

West L, Pierce S, Yin Y, et al. From fat to fit: a low fat diet decreases tumor growth in mice with endometrial cancer. In: Proceedings from the SGO 2018 Annual Winter Meeting; February 8-10, 2018; Aspen, Colorado.