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Environmental influences on breast cancer risk — the evidence mounts
By John Yewell
Fenton addressed the elusive link between breast cancer and chemical exposure. “We may never have enough evidence to prove that something caused a disease, because we’re exposed to so many things in mixtures,” she said. “We need to move from the idea of strict causation to one of increasing or decreasing risk.” (Photo courtesy of Steve McCaw)
The mammary gland is unusual in the number of organs it receives signals from and the number of hormones the tissue responds to. (Photo courtesy of Sue Fenton)
As a kid growing up on a farm in Wisconsin, Sue Fenton was fascinated by dairy cows. “I always wondered how they could produce milk nearly year-round, for year after year,” she said.
Now a Ph.D. and a reproductive endocrinologist with the National Toxicology Program (NTP) at NIEHS, Fenton highlighted the cutting edge of mammary gland research, guest editing “Environmental Impact on Breast Development and Disease,” a July 2015 special issue of the journal Reproductive Toxicology.
The extent of the problem was spelled out in a summary article co-authored by Linda Birnbaum, Ph.D., director of NIEHS and NTP, and Gwen Collman, Ph.D., NIEHS Director of Division of Extramural Research and Training.
“Despite decades of research, the number of women diagnosed with breast cancer continues to rise,” they wrote. “In 2014, an estimated 233,000 women and 2400 men in the United States were diagnosed with breast cancer, and approximately 40,000 women died from it.”
It’s complicated
According to Fenton, the breast’s susceptibility to cancer is exceptional among the reproductive organs. “Other tissues such as the ovary, testis, and uterus are also critical for reproduction; yet, they do not display the high degree of carcinogenicity in humans as seen in the breast,” she wrote in her editorial.
The reason, she explained, is the complexity of the tissue, which makes it difficult to get a handle on the reasons for its carcinogenicity.
“There are many cell types in the mammary gland, plus its own fat, which means it has its own hormones from fat. And the breast actually receives signals from about ten different organs,” she said. “This is one of the reasons why more people don’t do this kind of work. You can’t just take the epithelial cells out of their tissue, use them in culture, and expect them to behave as they would in the body, as you can do with many other tissues.”
Timing matters
To better understand how endocrine disrupting chemicals (EDCs) cause cancer, the scientists in the special issue relied on animal studies and on associations found in cohorts of children.
“We looked at early exposure to a chemical, as opposed to at the time of diagnosis, and we’re finding some strong risk factors associated with that,” Fenton said. “Fetal exposure, or in utero exposure, or prenatal — one of those words is used in almost every one of these studies. I didn’t ask for such papers. It’s just that people are recognizing the importance of it, and they are setting their experiments up that way.”
Birnbaum and her co-authors reinforced the importance of timing in their summary. “There are windows of susceptibility during the life course,” they wrote. “To understand the role of the environment in the etiology of breast cancer, we must understand life stages when the breast is most susceptible to environmental insults.”
A sense of urgency
The evidence for the role of chemical exposure shows up in outcomes such as early puberty and accelerated breast development, which Fenton said is rampant across the globe. “It’s happening much faster than gene change, it’s not genetic,” she said. “It’s definitely the environment playing a role.”
Over the years, with growing evidence for the environmental contributions to cancer, Fenton has acquired a sense of urgency. “It’s one of the most often diagnosed cancers in women, and we know so much less than we know about other cancers.”
Citations: Fenton SE . 2015. A special issue dedicated to a complex tissue. Reprod Toxicol. (54):1-5.
Forman MR, Winn DM, Collman GW, Rizzo J, Birnbaum LS. 2015. Environmental exposures, breast development and cancer risk: Through the looking glass of breast cancer prevention. Reprod Toxicol. (54):6-10.
(John Yewell is a contract writer for the NIEHS Office of Communications and Public Liaison)
A wealth of strong research
The issue includes a wealth of studies among its 18 papers. “I knew most of these researchers professionally, so thought they would send high quality manuscripts,” Fenton said. “I was right.” She was happy to note that the scientific community seemed to concur. After only two weeks, one of the papers had already been downloaded 263 times. The following papers are among those in the special issue.
- California breast cancer prevention initiatives: setting a research agenda for prevention , by P. Sutton, et al.
- In utero preeclampsia exposure, milk intake and pubertal development , by Jeremy Michals Schraw, et al.
- The mammary gland is a sensitive pubertal target in CD-1 and C57Bl/6 mice following perinatal perfluorooctanoic acid (PFOA) exposure , by Deirdre K. Tucker, et al.
- Prenatal Bisphenol A exposure delays the development of the male rat mammary gland , by Laura Kass, et al.
- Mixtures of environmentally relevant endocrine disrupting chemicals affect mammary gland development in female and male rats , by Karen Riiber Mandrup, et al.
- Estrogens in the wrong place at the wrong time: Fetal BPA exposure and mammary cancer , by Tessie Paulose, et al.
- Alteration of mammary gland development and gene expression by in utero exposure to arsenic , by Daniela A. Parodi, et al.
- Segregated responses of mammary gland development and vaginal opening to prepubertal genistein exposure in Bscl2 -/- female mice with lipodystrophy , by Rong Li, et al.
- Paradoxical zinc toxicity and oxidative stress in the mammary gland during marginal dietary zinc deficiency , by Zeynep Bostanci, et al.
- Alcohol intake stimulates epithelial proliferation in an authentic model of the human breast , by Anke Schennink, et al.
- Dietary exposure in utero and during lactation to a mixture of genistein and an anti-androgen fungicide in a rat mammary carcinogenesis model , by P. Phrakonkham, et al.
- Effect of maternal exposure to endocrine disrupting chemicals on reproduction and mammary gland development in female Sprague-Dawley rats , by Fabiana Manservisi, et al.
- Concentrations of environmental phenols and parabens in milk, urine and serum of lactating North Carolina women , by Erin P. Hines, et al.
- Application of Sholl analysis to quantify changes in growth and development in rat mammary gland whole mounts , by Jason P. Stanko, et al.
- Hypothesis: Activation of rapid signaling by environmental estrogens and epigenetic reprogramming in breast cancer , by Lindsey S. Trevino, et al.
- Evaluating chemical effects on mammary gland development: A critical need in disease prevention , by Gwendolyne Osborne, et al.
