Obesity and breast cancer: Linking inflammation to aromatase activity in cancer progression and therapy resistance

Abstract

Breast cancer affects an increasing number of women every year, and a major risk factor for this disease is obesity. I studied the connection between breast cancer progression and an obese microenvironment in ER+ breast cancer, which requires estrogen to grow. For one, consumption of energy and nutrients in excess of what is required by the body helps to fulfill a growing tumor's high energy demands. At the same time, accumulation of fat tissue not only allows for storage of excess energy, but also forms an endocrine tissue, providing hormones and growth factors that support tumor growth. Another way in which I found that obesity supports a tumor is by creating a chronic state of inflammation in the body. The tumor can manipulate the inflammatory environment to hide from the immune system, grow blood vessels, invade other tissues, and eventually spread to other organs. One type of immune cell called macrophages is found in the tumor environment and seems to produce a compound called PGE2, which stimulates the activity of aromatase. This enzyme plays an important role in the synthesis of estrogens. Based on my findings, I believe that obesity assists the cancer in sustaining an inflammatory environment full of macrophages releasing PGE2. High amounts of this compound then lead to stimulation of aromatase, and synthesis of greater amounts of estrogen. The tumor can use these estrogens to grow and progress to a more advanced stage. This knowledge can help us to discover more effective future treatments. Currently, breast cancer patients usually receive a primary treatment coupled with hormone therapy, which targets for example aromatase to disrupt estrogen synthesis and prevent cancer growth. However, many women are already therapy-resistant or become therapy-resistant over time, leading to a high potential for future relapse. More research is needed into the mechanisms behind resistance to aromatase inhibitors and other hormonal treatments. Additionally, factors such as a patient's weight, metabolic health, and potential inflammation, should be taken into account when conducting a risk assessment in the clinic, seeing as obesity has been linked to a greater breast cancer risk and cancer progression.