LOUISVILLE, Ky. – It seems like every day there is another item we encounter that can lead to cancer. In this Q&A, we dive into research being performed by Alexandra Nail, Ph.D., and Brian Dong, M.D., that focuses on the risks of exposure to heavy metals that may lead to cancer. Alexandra Nail is a postdoctoral fellow in the Department of Pharmacology and Toxicology at the University of Louisville School of Medicine. Dr. Brian Dong is a breast medical oncologist for UofL Health – Brown Cancer Center and an assistant professor of medicine at the UofL School of Medicine.
Q: We are constantly hearing about everyday items that have toxins and could cause cancer. What are the top things you recommend that anyone should limit exposure to in order to reduce their cancer risk?
Brian Dong: Breast cancer rates in the U.S. are higher than other parts of the world. We know there’s some environmental cause, but the exact causation of things like heavy metals, radon, radiation, etc. are still being studied. It’s going to take years to get significant results.
To reduce your overall cancer risk, use sunscreen to limit exposure to the sun; eat a balanced diet to limit highly processed foods; be careful what supplements you use; and stay away from smoking and tobacco.
Q: What is the focus of your research, and what have you discovered about the effects of heavy metals?
Alex Nail: Lately, I have been focusing on how environmental exposure to toxic heavy metals promotes triple-negative breast cancer by disruption of DNA double-strand break repair. Triple-negative breast cancer is a notoriously aggressive and hard-to-treat breast cancer because it lacks targeted therapies, unlike other breast cancer subtypes (e.g. Estrogen Receptor and Progesterone Receptor positive, and HER2—now named ERRB2—positive breast cancers). Triple-negative breast cancer is linked to defects in DNA double-strand break repair. People who are at a higher risk of developing triple-negative breast cancer are likely to have inherited mutations in genes that are important for DNA double-strand break repair (e.g., BRCA1). I have found that long-term exposure to cadmium, a toxic heavy metal, significantly reduces activation of proteins needed for DNA double-strand break repair and signaling. Both BRCA1 and TP53 are proteins whose inactivation is classically linked to increased triple-negative breast cancer incidence.
Q: Where do we find these heavy metals? What can be done to avoid them?
Alex Nail: In the U.S., someone is most likely to be exposed to heavy metals if they live near industrial facilities. Furthermore, my toxic metal of interest, cadmium, accumulates in tobacco leaves, so smokers are at a significantly higher risk for cadmium exposure. Changing controllable lifestyle factors such as smoking cigarettes is key for reducing risk based on my most recent research. Unfortunately, other factors, such as living near industrial facilities, are often less controllable, particularly for individuals whose housing options are limited by educational or financial constraints.
Q: Dr. Nail’s research suggests that individuals who live near industrial facilities could be at a higher risk of cadmium exposure, therefore, also having a risk of triple-negative breast cancer. What are you seeing in your patient population? Have you seen any increase in triple-negative breast cancer patients?
Brian Dong: It’s too early to make this jump. I believe there are many studies to suggest correlation with plenty of chemicals to cancer risk for factory workers, but there isn’t a certain level of exposure that I’m aware that will increase your risk by a certain amount for breast/lung/colon cancer. I would say asbestos is probably the one major exception to this with a clear link to mesothelioma.
Q: How does this knowledge relate to what we’re seeing in breast cancer, especially for those living in Kentucky (where applicable)?
Alex Nail: Environmental cadmium exposure likely contributes to triple-negative breast cancer initiation by inhibiting DNA double-strand break repair protein function whose inactivation, due to mutation, is already known to be associated with increased triple-negative breast cancer risk.
Q: What do you find most concerning, and what do future studies look like?
Alex Nail: Future studies need to test whether there is a connection between higher cadmium levels in breast, triple-negative breast cancer incidence, and inhibition of DNA double-strand break repair protein activation in breast tissue. Establishing a causation between cadmium exposure and triple-negative breast cancer incidence is likely going to take at least another decade of work, possibly longer. I wish research timelines were quicker, but they aren’t.
Q: What kind of impact could your research have? Why is it important?
Alex Nail: Adding cadmium exposure to preventative screening risk assessments could explain why some specific populations of women are at higher risk for developing triple-negative breast cancer, particularly African American women (2-3x higher risk). African American women are also more likely to live in areas with higher heavy metal pollution. Establishing these “full circle” connections is important for establishing a causation between cadmium exposure and triple-negative breast cancer incidence.
Future research in my lab may also allow for broadened use of PARP inhibitors to treat cadmium-induced triple-negative breast cancers. PARP inhibitors are commonly used to treat triple-negative breast cancers in cancers with inactivated BRCA1 protein due to BRCA1 gene mutations. However, we still must first establish whether PARP inhibitors are effective in treating cadmium-induced triple-negative breast cancer.
Q: What is currently being studied in clinical trials for triple-negative breast cancer? What advances have been made in terms of treatment?
Brian Dong: Novel targets called antibody drug conjugates are the major innovation for triple-negative breast cancer. We know they work very well for people with advanced disease, but we want to figure out if they work well as an earlier line of treatment and if they can even work for people with locally advanced disease to kill of cancer cells in a curative setting. There are plenty of environmental factors involved, but it takes a lot of time and money to study that. We hope to soon launch a study that will track our high-risk patients’ heavy metal exposures.
To learn more about research studies and clinical trials at the University of Louisville and UofL Health, visit UofLHealth.org/Research.
