Last summer, I attended (virtually and in-person) the mega yearly conference of oncology: The 2013 ASCO Annual Meeting. The American Society of Clinical Oncology—a misnomer, as it is a worldwide organization—is the leading oncology organization that pulls together all the specialties that touch people with cancer. The traffic was even busier than normal in Chicago as 30,000 cancer-minded people (healthcare workers, companies, and advocates) swarmed to learn about the latest research in the field.
Many women struggle with weight gain (including myself) independent of cancer, but when you add chemotherapy, steroids, sudden menopause, fatigue and medications that promote weight gain, it can feel nearly impossible to manage. Weight gain is in the top 3 concerns I see reported in our survivorship clinic behind fatigue and pain. Many studies show that less than 50% of women actually gain weight during treatment for breast cancer—which is contrary to what most people think will happen with cancer treatment. While I routinely discuss this with the people I see in clinic, I feel it is going to be increasingly important to have a coordinated effort with the oncology team to promote healthy behaviors as part of the prevention and treatment of breast cancer.
The data is striking, both from a breast cancer prevention and a recurrence standpoint. One of the topics discussed at the ASCO meeting, during presentations by Dr. Jennifer Ligibel, Dr. Andrew Dannenberg and Dr. Howard Strickler, was the link between obesity, insulin, inflammation and breast cancer. I find that topic so fascinating, not only because of the cool physiology, but because it is something breast cancer patients can have some control over!
I want to break down what was presented because it certainly helped me to understand the relationship! Knowledge is power, and this knowledge motivates me to seriously think about what I am putting into my mouth on a daily basis. What we eat, and how much we eat and move, impacts so many things—down to the cellular level.
Obesity causes inflammation in the breasts. Dr. Andrew Dannenberg discussed that when we gain weight, our fat cells enlarge. Or, rather, they enlarge to a point—and then die. Once they die, cells called macrophages come to clean them up and, in the process, cause inflammation (by secreting inflammatory proteins called cytokines). Inflammation is our body’s way of handling injury, but when the body is in a chronic state of inflammation, it results in a cascade of unwanted events.
Inflammation turns on aromatase. Dannenberg presented his research that shows that these inflammatory cytokines (proteins) in the breasts can turn on an enzyme called aromatase.
Turning on aromatase increases estrogen formation. Estrogen causes cells to multiply and if there happens to be a cell that has cancer causing mutations, then those cells will have a chance to grow into a tumor. This is why aromatase inhibitors (or blockers) like anastrazole, exemestane, etc. are believed to reduce the risk of breast cancer from coming back.
Insulin levels explain another piece of the puzzle. Insulin is a hormone secreted by our pancreas that helps us regulate the amount of sugar in our blood. When we have extra sugar in our blood, the insulin will help the body store the sugar for later use. Our body can become resistant to insulin, which means that it takes more and more insulin to regulate the sugar in our bloodstream. One factor that causes “insulin resistance” is weight gain. There have been 5 studies assessing fasting insulin levels and breast cancer (Goodwin, 2002; Pasanisi, 2006; Pollak, 2006; Irwin, 2009; Borugian, 2003). These show a correlation with higher insulin levels and worse breast cancer prognosis, and vice versa.
Potential targets for cancer treatment
Metformin: Metformin is a medication that has been used for diabetes. It works by lowering the liver’s production of glucose (the body’s sugar), decreasing absorption of sugar in the intestines and increasing the body’s sensitivity to insulin. A large clinical research trial, MA32, is testing metformin’s use after breast cancer surgery to see if it will reduce the risk of recurrence.
Aspirin and other anti-inflammatory medications: It is also thought that there may be a role for aspirin or other anti-inflammatory medications in the prevention and treatment of breast cancer. Suggestions from studies indicate that there may be improvement in survival with simple medications like aspirin, but more studies are needed to tell for sure. There is a study underway looking at DHA (one anti-inflammatory medication) to see if it causes changes in breast cancer inflammation. This trial is very intriguing and I will anxiously await the results.
Lifestyle interventions: In several studies, exercise also significantly decreases insulin levels. Risks of breast cancer recurrence and death are lowered by physical activity. Data from 2 large trials with women with breast cancer also show that women who lost weight (but not those who just changed their diet) had a decreased recurrence. (WINS –Women’s Intervention Nutrition Study and WHEL –Women’s Health Eating and Living Study). Dr. Ligibel made the point that, given the current data, we really need to look at obesity treatment as a treatment for cancer. I would totally agree!
This is an evolving area and I think we will see more interventions targeting these pathways and a lot more explanation as to how this happens in the future. In the meantime, I am excited about the upcoming trial that the Edith Sanford Breast Cancer initiative will be opening—using wellness coaches to help patients with breast cancer lose weight during treatment to see if it can impact the markers these scientists discussed in this session at ASCO.