Breast cancer and obesity: A discussion with researcher, Dr. Liza Makowski

By John Murphy, MDLinx
Published April 11, 2017

Key Takeaways

Background: Obesity is linked to increased risk for triple-negative breast cancer, as well as increased risk of vascular invasion, metastasis, and mortality in breast cancer patients. At the recent American Association for Cancer Research (AACR) Annual Meeting 2017 recently held in Washington, DC, several researchers addressed the role of adipose tissue and obesity in the growth of tumors in the fatty-tissue “microenvironment.”

To see more coverage of the American Association for Cancer Research (AACR) Annual Meeting 2017, please click here.

In this interview, one of those researchers, Liza Makowski, PhD, explains why it is becoming increasingly apparent that the microenvironment surrounding tumor cells strongly influences tumor onset and progression. Her latest research investigates whether the tumor itself—or its surrounding microenvironment—accelerates cancer in adipose tissue.

MDLinx: Can you please define the microenvironment and why it is important?

Dr. Makowski: The adipose microenvironment includes adipocytes and adipose-associated stromal and vascular components, such as fibroblasts and other connective tissue cells, stem cells, endothelial cells, innate and adaptive immune cells, and extracellular matrix components.

Much of the cancer research in past decades has focused on the tumor itself. We are currently in a new era where the surrounding “soil” (the microenvironment) is becoming as important to target as the “seed” (the tumor).

MDLinx: What did your study conclude?

Dr. Makowski: We had previously shown that obesity can drive early tumor onset and/or speed up tumor growth akin to what has been shown for humans with triple-negative breast cancer. We wanted to test whether the obesity-driven effects were due to signals in the tumor itself or if changes to the microenvironment around the tumor could alter growth.

To find out, we used a model of triple-negative breast cancer wherein we took cells from a tumor in a lean mouse and injected those cancer cells into the mammary glands of three groups of mice on different diets: lean mice, obese mice, and mice that were formerly obese and went through a diet switch-associated weight loss.

What we found was interesting. In our study, the same exact cells injected into obese or lean microenvironments showed us that obese tumors again grew faster—but in the formerly obese mice, tumors grew the same as if they were lean. This means that some drivers of obesity-associated tumors could be reversed, at least in the context of our study.

When we looked at protein and mRNA expression, we also showed that the tumors themselves were not that different amongst the three diet groups. But there were tremendous differences in the mammary gland surrounding the tumors that paralleled the tumor growth findings. This suggests that growth factors or other cells in the microenvironment control tumor growth rather than changes intrinsic to the tumor cell line injected.

MDLinx: One of the findings in your abstract was that mean final tumor volume in formerly obese mice did not differ significantly from that of either lean or obese mice. Can you elaborate?

Dr. Makowski: Since we wrote the abstract, the findings became more clear with additional data (unpublished; manuscript in preparation). Our recent data show, in fact, that the tumors in the obese models grew faster and got larger than in mice that were lean (either by remaining lean throughout the study or by the diet switch-induced weight loss in the formerly obese group).

MDLinx: What implications does your study have for women who are obese? Do these implications also apply to women who are overweight but not obese?

Dr. Makowski: Great question. In this study, we used a pre-clinical model of mice to test our hypothesis, so it is hard to extrapolate exactly to patients. However, for patients who are obese or overweight, losing weight or maintaining a lean weight is a good idea for many diseases, including heart disease, diabetes, and others.

MDLinx: What research will you conduct to follow up on this investigation? How will you search for the obesity-related cancer-growth driver(s) in the microenvironment?

Dr. Makowski: One cell of the microenvironment that is of great interest to my lab is the macrophage—a white blood cell that can be present in lean adipose tissue but which greatly increases in obesity. Macrophages also infiltrate tumors and help not only drive tumor growth and metastasis but also suppress other tumor-killing cells from acting. Much more work needs to be completed on this important immune cell, especially in finding ways to change its function to reduce tumor growth without harming natural immune defenses.

MDLinx: You chaired a symposium at AACR on this topic. What were the most important findings you heard from the other presenters?  

Dr. Makowski: We had a standing-room-only session, which showed the interest in understanding the effect of obesity and inflammation on cancer risk and progression. One of the most important take-home messages from the symposium is that obesity is not a one-size-fits-all category—that is, not all body types are alike, so the immune or stem cell components of tissues such as adipose must be further studied.

For example, Andrew J. Dannenberg, MD, showed findings that even lean women have immune cell infiltration in the mammary glands. Thus, it is important for us to further understand when, how, and where these immune and stem cells of the microenvironment are working to drive cancer onset and progression.

Immunotherapy to change the immune microenvironment is the hottest area of cancer research and one that will hopefully improve patient outcomes.

About Dr. Makowski: Dr. Makowski is an associate professor in the Department of Nutrition at the Gillings School of Global Public Health and a researcher at the Lineberger Comprehensive Cancer Center at the University of North Carolina at Chapel Hill, in Chapel Hill, NC.

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