More Evidence on Environmental Toxins and Breast Cancer

Fran Lowry

February 28, 2019

Two studies shed new light on the role of environmental toxins and breast cancer risk. One study investigated phthalates, the other examined DDT (dichlorodiphenyltrichloroethane).

Phthalates are virtually ubiquitous and are found in shampoo, makeup, vinyl flooring, toys, medical devices, and car interiors. Nearly everyone in the United States is exposed, primarily by eating and drinking food and liquid that have come in contact with products containing the chemicals.

Phthalate exposure has been implicated in a number of diseases and medical conditions, including infertility in men.

The new study, described as the largest study to date on phthalates and postmenopausal breast cancer, suggests that the chemicals have no effect on a woman's risk for breast cancer that develops after the menopause.

However, the results leave open the question of a possible relationship between phthalate exposure and breast cancer in premenopausal women, according to lead author Katherine Reeves, PhD, MPH, from the School of Public Health and Health Sciences at the University of Massachusetts, Amherst.

Dr Katherine Reeves

"We found no statistically significant association between phthalate exposure and breast cancer, and while this does not rule out a smaller effect, I think it rules out a very large effect," Reeves told Medscape Medical News.

"For example, when we think of smoking and lung cancer, that is a really strong effect, but the relationship between phthalates and postmenopausal breast cancer, based on our study, is certainly unlikely to be that large. However, we could not rule out a smaller effect on breast cancer risk," she said.

This is because phthalate exposure changes from day to day and the substance is metabolized very quickly and is excreted in the urine within a matter of hours, Reeves added.

This study was published online January 10 in the Journal of the National Cancer Institute.

Study Details

In their nested case-control study, Reeves and her research team took frozen urine samples that had been provided many years ago by women taking part in the Women's Health Initiative (WHI).

They measured levels of 13 phthalate metabolites and creatinine in the urine of 419 women who were diagnosed with invasive breast cancer after year 3 of the WHI and in the urine of 838 healthy control persons. Two or three urine samples from each participant, taken at baseline, year 1, and year 3 of the WHI, were assessed.

The average age of both case patients and control persons was 62 years. Case patients were more often obese, current smokers, and less physically active than control persons.

"The women had donated these samples at a time when everyone was healthy. The important thing to recognize is that prior studies had done this retrospectively, meaning that they were measuring phthalate exposure after the women had been diagnosed with breast cancer. This isn't the best approach for phthalates, because phthalate exposure can happen through medical equipment and medication, and so what you might be measuring only reflects the fact that they've recently been diagnosed with breast cancer and not something that could be causing their disease," Reeves explained.

Concentrations of phthalate biomarkers were similar between case patients and control persons. There was no association between these biomarkers and increased breast cancer risk, either overall or by disease subtype.

Adjusted odds ratios (ORs) for the different phthalate biomarkers ranged from 0.85 (95% confidence interval [CI], 0.38 – 1.91) to 1.04 (95% CI, 0.92 – 1.17).

Similar results were found in analyses that were restricted to disease subtypes, nonusers of postmenopausal hormone therapy, body mass index, and cases that were diagnosed within 3, 5, or 10 years.

"Our null results persisted, regardless of the analytic technique used, and so we conclude that any large increases in breast cancer risk associated with phthalate exposure are unlikely," Reeves said.

"I think we have better information than most studies because we did use two or three measurements per person. The measures we have are reflective of very recent exposure, so I feel pretty confident that there is not a very large effect of phthalates on postmenopausal breast cancer, but we can't rule out a smaller effect. It's also important to recognize that we were only looking at women who were postmenopausal, so our results don't necessarily apply to younger women," she said.

"Also, we were measuring phthalate exposure at a time when women were already postmenopausal, between the ages of 50 and 79. Increasingly, we are understanding that the key window for breast cancer risk might be much younger, during adolescence or before a first pregnancy. We were not able to look at that at all in this study," she said.

Going forward, Reeves said she would like to study younger patients to see whether earlier phthalate exposure affects later breast cancer risk.

"Phthalate measurements can vary, so if there is a way to get more urinary measurements over a period of time, that would allow us to better characterize the women who are most exposed and those who are least exposed, and that will allow us to get a better answer," she said.

Ubiquitous DDT and Breast Cancer

The second study investigated exposure to DDT, an organic insecticide that was widely used for agriculture. It was banned in the United States in 1972 and was subsequently banned worldwide. However, it persists in the food chain, and populations are therefore continuously exposed.

This study, which was also published in the Journal of the National Cancer Institute, found that DDT exposure was associated with breast cancer through age 54 years and that the risk depended on the time of first exposure.

Women exposed before age 14 years, particularly during infancy (birth to age 3 years) and early childhood, were most likely to develop premenopausal breast cancer. Those who were exposed after infancy were at increased risk of developing cancer later, at age 50 to 54 years.

Dr Barbara Cohn

"Timing is important, and we know that if harmful exposures occur at times when breast tissue is rapidly changing, such as during puberty or first pregnancy, this can impact breast development in ways that can result in cancer," lead author Barbara A. Cohn, PhD, of the Public Health Institute's Child Health and Development Studies, Berkeley, California, told Medscape Medical News.

"Our results suggest that DDT affects breast cancer as an endocrine disruptor and that the time between first exposure and cancer is around 40 years," Cohn said.

In an article published in 2007 in Environmental Health Perspectives, Cohn and her colleagues reported a fivefold increased risk for breast cancer in women who were younger than 14 years at the time they were first exposed to DDT.

A study by Cohn and her group that was published in 2015 in the Journal of Clinical Endocrinology and Metabolism reported an increased breast cancer risk in women who were exposed in utero to DDT.

In the current study, the researchers extended their observation to patients with breast cancer that was diagnosed early after menopause (ages 50 to 54 years). Their aim was determine whether age at diagnosis modifies the interaction of DDT with age at exposure.

The researchers analyzed stored blood samples that had been collected from 1959 to 1967 during pregnancy at each trimester and in the early postpartum period.

They also used state records to identify 153 cases of breast cancer diagnosed from 1970 to 2010 in women aged 50 to 54. They then matched each of patient with 432 comparable control persons who did not develop cancer.

Their results showed that for early postmenopausal breast cancer, DDT was associated with an almost twofold increased risk for all women (OR for women aged 50 to 54 = 1.99; 95% CI = 1.48 – 2.67).

This association was accounted for by women who were first exposed to DDT after infancy (for patients aged 50 – 54 who were first exposed to DDT after infancy, OR = 2.83, 95% CI = 1.96 – 4.10; for patients aged 50 – 54 who were first exposed to DDT during infancy, OR = 0.56; 95% CI = 0.26 – 1.19).

In contrast, for premenopausal breast cancer, DDT was associated with risk among women younger than 50 years who were first exposed during infancy through puberty, but not after (OR = 3.70; 95% CI = 1.22 – 11.26).

All Were Exposed, but Not All Got Cancer

Virtually everyone has been exposed to DDT, but not everyone gets cancer, Cohn said. Important questions concern what is protecting some people and why others are vulnerable to the deleterious effects of the chemical.

"Some women are exposed in utero, some in early childhood. Some do not develop cancer. If we can understand how this happens, maybe the holy grail would be to develop a biomarker for your past risk. We are working on that, trying to look at what the blood chemicals look like in the women who got sick compared to the ones who didn't, in relation to their exposure to DDT," Cohn said.

"Everyone in our cohort was exposed. Everyone in the world was exposed in the 1960s. But not everyone got sick. We are trying to understand what is the woman's response to these chemicals that hurt her. If we can find a biomarker like that, it might be possible to find women with that biomarker and perhaps figure out how to prevent her from developing cancer," she said.

The study by Reeves et al was supported by the National Institute of Environmental Health Sciences. The study by Cohn et al was funded by the National Institute of Environmental Health Sciences and the California Breast Cancer Research Program through the California Breast Cancer Research Program. The authors have disclosed no relevant financial relationships.

J Natl Cancer Inst. Published online January 10, 2019. Reeves et al, Abstract; Cohn et al, Full text

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