Experts Evaluate Link Between Phthalates and Breast Cancer

In an interview with Oncology Learning Network, Katherine W. Reeves, PhD, MPH, Associate Professor, Department of Biostatistics & Epidemiology, School of Public Health and Health Sciences, University of Massachusetts Amherst, talked about her team’s findings from a prospective subgroup analysis of women enrolled in the Women's Health Initiative (WHI).

Citing increasing evidence supporting the potentially carcinogenic effects of certain phthalates, Dr Reeves and colleagues conducted a study to fill the gap in literature regarding the link between phthalates and breast cancer risk.

What existing data led you to evaluate the carcinogenic effects of certain phthalates, and their association with breast cancer?

There is growing evidence from laboratory and animal studies that certain phthalates may act like estrogens and cause breast cancer cells to grow. A few studies had looked at whether phthalates were related to breast cancer in humans, but these had some important limitations.

To measure phthalate exposure in humans we measure levels of phthalate metabolites in urine. Because these chemicals are excreted by the body fairly quickly, this only gives us a sense of exposure within the past day or so.

Previous studies had measured phthalate exposure after women were diagnosed, which isn’t when exposure could have caused their breast cancer. Because phthalate exposure is so common in the United States, we thought it was important to conduct a study that would be able to tell us more about whether phthalates can cause breast cancer.

Please briefly describe the methods of your study. What particular phthalates did you look at, and what consumer products are they most frequently found in?

We accessed samples from women who participated in the WHI, a large, prospective cohort study that, between 1993 and 1997, enrolled 161,808 women aged 50 to 79 years. Some of these women provided urine samples at their study visits.

We retrieved these stored urine samples from 419 women who were later diagnosed with breast cancer and from 838 women who were not. Each woman included in our study had provided 2 or 3 urine samples, all of which were collected before anyone was diagnosed with breast cancer.

We measured a panel of 13 urinary phthalate metabolites as indicators of exposure to the following phthalates—dibutyl phthalate, benzylbutyl phthalate, di-isodecyl phthalate, di-isononyl phthalate, di(2-ethyl hexyl) phthalate, diethyl phthalate, di-n-octyl phthalate, and di-isobutyl phthalate. These phthalates are found in a variety of consumer products, including personal care products, vinyl flooring, industrial solvents, and plastic tubing.

What are the possible real-world applications of your findings? Were any of them particularly surprising?

Overall, we did not find a large increase in breast cancer risk associated with phthalate exposure, although we weren’t able to completely rule out a smaller effect. We were surprised at how much women’s phthalate-exposure varied over time; very few women had similar levels in repeated measurements over a 3-year period. This made it challenging to characterize the people who were the most exposed and who were the least, which is what we need to be able to do in order to evaluate whether higher phthalate exposure is related to breast cancer risk. Using 2 to 3 samples per person helped, but it wasn’t fully able to overcome that challenge. There is still significant work to be done, and this is just an important step in that process.

Do you and your co-investigators intend to expand upon this research? If so, will you be incorporating any new phthalate metabolites, end points, or patient populations?

Our work raised as many questions as it answered, and we are planning to continue our research to understand whether phthalates contribute to breast cancer risk. It will be important to include younger women in future studies and also to measure exposure at younger ages.

In addition, there are many other chemicals that laboratory and animal studies suggest might affect breast cancer risk, such as bisphenol-A and parabens, yet these have not been fully studied in humans.

We all continue to be exposed to these chemicals, and it is incredibly important to use carefully designed studies to get a definitive answer.