Researchers at City of Hope are investigating the influence of hormone-mimicking chemicals during sensitive stage in women’s lives. 

Approximately 30 percent of breast cancers are diagnosed during menopause, a stage in life marked by a decline in the body’s production of estrogen and progestin. Growing evidence suggests it might also be a time when the breast is particularly susceptible to chemical exposures that increase breast cancer risk.

To better understand this relationship, researchers at City of Hope in California, one of the nation’s comprehensive cancer centers, are investigating whether exposures during menopause to certain types of chemicals, in particular endocrine disruptors (EDCs) that interfere with the body’s system of hormones, contribute to the development of breast cancer.

Led by molecular epidemiologist Dr. Susan Neuhausen and cancer biologist Shiuan Chen, the researchers are focusing on two types of chemicals: a class of flame retardants called PBDEs (polybrominated diphenyl ethers) that are widely used in textiles, electronics, and building materials; and BPA (bisphenol A), a chemical commonly-found in plastics, food cans, and thermal paper receipts.

“The menopausal transition is an important window,” says Neuhausen. “Consider the Women’s Health Initiative, a long-term national health study that showed women who used hormone replacement therapy had an increased risk of postmenopausal breast cancer. Because PBDEs and BPA are chemicals that mimic estrogen, we hypothesize they could also increase the risk of breast cancer,” she says.

The City of Hope project is one of six research projects supported by the Breast Cancer and the Environment Research Program (BCERP), a joint effort co-funded by the National Institute of Environmental Health Sciences and the National Cancer Institute.

Exposure to PBDEs has been linked to a variety of developmental problems, including hyperactivity, poor attention, and learning difficulties in children. The City of Hope team hopes to expand research on the health effects to include breast cancer. Although PBDEs were phased out in 2006 due to health concerns, Neuhausen says the chemicals persist in the environment and in people’s bodies, and their presence in old furniture and other products means that people continue to be exposed.

BPA has also been associated with neurological and developmental problems. Concern among consumers about the BPA’s impacts on human health has risen sharply over the last several decades. Although, the U.S. Food and Drug Administration prohibits its use in baby bottles and children’s drinking cups, exposure in the population is widespread due to the chemical’s use in many other types of common products.

Neuhausen and her colleagues are investigating the potential effects of these two chemicals on breast cancer from multiple angles. The researchers are analyzing blood samples from participants in the California Teachers Study, a cohort of women that scientists have been following since 1995, looking for changes in gene expression and hormone activity associated with exposures. “Given that Californians probably have some of the highest blood levels of PBDEs than any other population in the world as a result of the state’s past flammability standards for furniture, it makes sense to work with the Teachers Study,” says Neuhausen.

The researchers are also doing studies in breast cells to understand the mechanisms by which these chemicals contribute to cancer development, as well as studies in mice to discern how PBDEs and BPA alter the mammary gland. Preliminary data suggests PBDEs cause more terminal end buds in the mammary gland, which may in turn lead to an increased risk of breast cancer.

While many companies have substituted PDBEs and BPA in their products with other compounds, the replacements often raise similar health concerns. Neuhausen says her team’s findings could be relevant to these newer replacements as well.

The project has assembled a Community Leadership Committee (CLC) that includes organizations representing Chinese, Latina, African-American, and Non-Hispanic White communities. The committee members provide guidance on how to communicate risk factors and the science, help with the development of educational materials including the project’s website, and recruit community members for focus groups. 

“It’s been very successful because these groups are not only helping us, but also they are learning about other organizations that are engaged in this issue,” says advocacy partner Michele Rakoff, executive director at Breast Cancer Care & Research Fund. “The CLC has really helped bridge communication across diverse communities.” Rakoff is also taking knowledge gained from the project and disseminating it through an educational program. The program partners universities and their magnet schools to introduce students to information about breast cancer and the environment.

Another BCERP site, the Georgetown Lombardi Comprehensive Cancer Center, is also looking at menopause as a susceptible time in life, with a focus on exposure to metals. “Menopausal women are not a population that has been really well-studied outside of hormone replacement therapy,” says Rakoff. “So the BCERP program is really helping us understand menopause as a risk factor.”

The co-principal investigators on the City of Hope project are Susan L. Neuhausen, Ph.D., The Morris & Horowitz Families Professor in Cancer Etiology & Outcomes Research, and Shiuan Chen, Ph.D., professor and chair of the Department of Cancer Biology. Community advocate and Executive Director at Breast Cancer Care & Research Fund Michele Rakoff partners with the researchers to help design the research and disseminate results.

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