Meyer’s lab studies how environmental stressors affect molecular and cellular processes — especially mitochondrial stress and DNA damage — as well as whole organism outcomes. (Photo courtesy of Steve McCaw)

Researchers supported by NIEHS are working to gain a deeper understanding of environmental factors with potential links to breast cancer. They and others spoke March 9 during “Breast Cancer and the Environment,” a symposium sponsored by the Duke University Program in Environmental Health and Toxicology and the Duke Superfund Research Center.

Joel Meyer, Ph.D., director of graduate studies in Duke’s Nicholas School of the Environment, led the symposium.

“Twin studies and other evidence have indicated that genetics alone account for approximately 15 percent of breast cancer cases,” he said, explaining the choice of topics for the annual symposium.

“The speakers in our symposium did a wonderful job of covering research from mechanistic laboratory work to three-generation epidemiological studies that cast light on the contribution of environmental exposures to breast cancer,” Meyer added.

Sensitive to endocrine disruptors

Fenton is an expert in mammary gland development and the impacts of chemical exposures. (Photo courtesy of Steve McCaw)

Sue Fenton, Ph.D., head of the National Toxicology Program Reproductive Endocrinology Group, spoke about her lab’s research on mammary gland development. The mammary gland can be a sensitive target for endocrine-disrupting chemicals, she said. Endocrine disruptors are compounds that can interfere with hormones in the body.

Early life exposure to bisphenol A (BPA) resulted in mammary gland tumors and increased sensitivity to estrogens in rodents studied by Fenton and her colleagues. BPA is widely used in manufacturing plastics and other products. The team also studied several replacement chemicals for BPA, including bisphenol AF (BPAF) and bisphenol S (BPS).

According to Fenton, these replacements may not be any less risky than BPA when it comes to breast cancer. “The worst part about these chemicals is they’re either more or equally active as BPA in terms of their estrogenicity,” she reported.

Mammary glands are targets for other chemicals as well, Fenton explained. For example, early life exposure of mice to perfluorooctanoic acid, or PFOA, which was previously used to manufacture nonstick coatings, led to later life deficits in mammary gland development.

Better research methods

Melissa Troester, Ph.D., a lead researcher at the University of North Carolina at Chapel Hill (UNC) Breast Cancer and the Environment Research Program, described her work to develop an atlas for precancer states of the breast. She said that studying the breast’s susceptibility to environmental exposures calls for understanding how exposures in early life, such as before birth and in early childhood, can affect breast cancer risk later on.

Mammographic density, which refers to the appearance of breast tissue on a mammogram, is another area of Troester’s research.

“Mammographic density is one of the strongest risk factors for breast cancer, and it isn’t fully understood why that’s the case,” Troester said. Combining mammographic density with precancer breast tissue samples may help researchers develop new biomarkers for studying the environment’s role in the disease.

Air pollution and breast cancer

White described her ongoing studies of the effects of mixtures on breast cancer. (Photo courtesy of Steve McCaw)

Alexandra White, Ph.D., a postdoctoral fellow in the NIEHS Epidemiology Branch, highlighted airborne metals as a potential risk factor. White began by explaining that rare genetic mutations such as the BRCA1 gene are responsible for only 5 to 10 percent of breast cancer cases. “Genetics is important, but we’ve long known that environment and lifestyle risks are also important for breast cancer,” she said.

According to White, environmental risk factors of breast cancer are understudied, including air pollution. So she decided to look at participants in the NIEHS Sister Study, which collects data on more than 50,000 women with sisters who have breast cancer.

By comparing air pollutants near the homes of women who had later breast cancer diagnoses, White and colleagues found associations between airborne metals like lead and cadmium and postmenopausal breast cancer.

Cohn presented research on how exposures during pregnancy can affect breast cancer risk across generations. (Photo courtesy of Steve McCaw)

Windows of susceptibility

A theme in many of the talks was that timing of environmental exposure plays a large role in breast cancer outcomes. Time periods during gestation, before puberty, and during pregnancy are critical windows for exposure, according to Barbara Cohn, Ph.D., from the Public Health Institute.

“Because of the timing of the development of the breast, if you insult it at one point in life, you may get a specific outcome,” she said, pointing to early puberty and altered lactation as two examples.

(Former NIEHS postbaccalaureate fellow Samantha Hall is a graduate student at Duke University and an NIEHS Special Volunteer.)