Studying Obesity and Breast Cancer Risk

Studying Obesity and Breast Cancer Risk

TO CONCLUDE OUR RECOGNITION OF OCTOBER’S NATIONAL BREAST CANCER AWARENESS MONTH, WE’RE VERY HAPPY TO HIGHLIGHT DR. KRISTY BROWN’S RESEARCH THAT EXPLORES WHY OBESE WOMEN ARE AT HIGHER RISK OF DEVELOPING BREAST CANCER.

Kristy A. Brown, Ph.D., is Assistant Professor of Biochemistry in Medicine at Weill Cornell Medicine. Her work aims to determine how adipose tissue can impact cancer cells, as well as the normal mammary gland, to explain why obese women are more likely to develop breast cancer and die from the disease.

We hope you enjoy learning more about Dr. Brown’s work.

Please tell us about your background and provide an overview of your work. 

My research focuses on understanding why obese women are at higher risk of developing breast cancer. Initial studies examined the role of metabolic pathways in regulating aromatase, the enzyme responsible for catalyzing the final step in estrogen synthesis, in the breast fat.

Important insights into this relationship were gained by studying adipose tissue of individuals with hereditary cancer syndromes, including Peutz Jeghers Syndrome (STK11 mutations) and Li-Fraumeni Syndrome (TP53 mutations). The discovery of metabolic sensors LKB1/AMPK as key regulators of aromatase and the impact of inflammation on this axis has provided a new molecular link between obesity and breast cancer.

Based on this work, my lab demonstrated that one of the most commonly used anti-diabetic drugs, metformin, inhibits estrogen production specifically in breast adipose stromal cells via effects on AMPK. More recently, the lab also discovered that the gut-derived hunger hormone, ghrelin, and its unacylated form, are potent inhibitors of estrogen production and adipose tissue inflammation, as well as tumor cell growth.

We are now pursuing work aimed at characterizing the role of adipose tissue in driving tumor development, growth and progression, as well as harnessing our understanding of the mechanistic link between obesity and breast cancer to identify novel therapies for breast cancer.

What makes your research unique? Can you share with us some recent findings?

Our work aims to determine how adipose tissue can impact cancer cells, as well as the normal mammary gland, to explain why obese women are more likely to develop breast cancer and die from the disease.

As such, my lab works at the nexus of obesity and breast cancer research. The integration of adipose and tumor biology research would not be possible without the advanced modelling of these systems ex vivo.

We work very closely with clinical teams at Weill Cornell Medicine and MSKCC to obtain valuable patient samples for the isolation of primary adipocytes, glandular epithelium, stromal vascular and tumor cells which are then grown in biologically relevant extracellular matrices in 3D.

Using these models, we have demonstrated that an obese breast microenvironment causes changes to “normal” breast epithelial cells that have previously been associated with the development of breast cancer. We have also utilized findings from our research to identify novel therapeutic approaches.

For example, the identification of a gut-derived hormone as a potential novel breast cancer therapeutic. Here again, it appears that culturing cells in a biologically-relevant 3D microenvironment affects response to treatment.

 What excites you about your work?

The most exciting aspects of my work include being able to make new discoveries and seeing how these can potentially affect the lives of cancer patients, not to mention the importance of being able to contribute to the development of the next generation of scientists. Some of our more recent discoveries include the identification of novel obesity-related factors responsible for driving tumor formation, growth and progression, as well as the characterization of their mechanism of action.

Being able see a discovery lead to the identification of a potential novel therapy for women who have limited options means that the impact of our work can go beyond the laboratory.

When thinking about your research, what are some recent breakthroughs that are propelling the field forward? How will they impact healthcare and patient care in the future? 

The emergence of precision medicine has tremendous potential in ensuring that different patients with heterogeneous tumors receive the most effective treatments possible.

In working with the EIPM, we are now in a position to start exploring predictors of response to various agents developed in my laboratory. Our work and that of others has also highlighted the importance of appropriate model systems for the study of disease. From patient-derived organoids to patient-derived xenografts, as well as biomimetic model systems such as those we have developed in collaboration with reconstructive surgeon and bioengineer, Dr. Spector, also from Weill Cornell Medicine, there is also great potential for the screening of clinical agents ex vivo so that we can identify treatments that will then be effective in patients.

What are the short-term challenges that your scientific field is facing?

Being able to access breast tissue from a diverse population of women is critical if we are to generalize our findings. Access to biospecimens that include tumor, adjacent normal and normal distal to tumors is key if we are to tackle questions of tumor-tumor microenvironment interactions. Of course, research is always dependent on funding.

What else would you like to share with Englander Institute for Precision Medicine team? 

There is so much value in working in an environment that brings together multidisciplinary researchers with a common goal of curing cancer. I am excited to work within the Englander Institute for Precision Medicine team!

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