About 25 to 30 percent of the 1 in 8 women that are annually diagnosed with breast cancer have familial cancer—i.e., one or more cases of cancer in their family. The other 70 to 75
percent have sporadic (non-hereditary) cancers, where lifestyle and environmental exposures
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modify risk. Dichloro-diphenyl-trichloroethane (DDT) is one such environmental exposure,
increasing the risk of breast cancer by sixfold if exposure occurs before the age of 14.
Endocrine-disrupting chemicals (EDCs) are of considerable research interest due to their
effect on the mammary gland and breast. EDCs can interfere with the synthesis, secretion,
transport, binding action, or elimination of natural hormones in the body that are responsible for maintenance of homeostasis, reproduction, development, and behavior.
Rodents are used to study the effects of EDCs on the mammary gland. Common structures of
the rodent mammary gland also found in humans are the mammary epithelium bud and the
terminal end buds (TEBs). TEBs are present just before, during, and right after puberty in
both female rodents and humans, and the length of time that they are present in the breast can affect the risk of carcinogenesis because of secondary exposures to carcinogens, including
UV light and x-rays.
Dioxin was one of the first chemicals shown to have an effect on the mammary gland. Initial studies demonstrated that early-life exposure to dioxin increases the multiplicity of mammary tumors in rats given a chemical carcinogen during a critical time window. Rodents exposed
on gestation day 15—the time at which the mammary bud is forming—showed the most
severe and persistent effects. These effects included altered maternal behavior and decreased milk production. Offspring of the exposed rodents also exhibited effects, such as increased
mortality rate and altered mammary gland development.
Atrazine, a chlorotriazine herbicide, is another compound shown to affect the mammary
gland in a manner similar to dioxin. Atrazine is a short-lived compound and documented
endocrine disruptor, interfering with pituitary hormone secretion and the luteinizing hormone surge. Its short half-life in adult rats and the reported effects from chlorotriazine metabolites prompted current atrazine exposure research.
Atrazine and other similar parent compounds are quickly metabolized in the environment and in the body. A study of rat offspring developmentally exposed to the atrazine metabolite
mixture (AMM) showed that it causes mammary gland abnormalities at 10- to 1,000-fold
lower doses than the parent compound.
Developing offspring are exposed to atrazine and its metabolites via amniotic fluid and milk, although the exposures (measured by levels of metabolites) via these two routes do not
appear to be the same. Short exposure times are sufficient to cause persistent effects in the mammary gland (3 days) and also the prostate (5 days). Mechanisms for these effects could
include potential changes in receptor populations following atrazine exposure that lead to
heightened sensitivity to the estradiol levels present in the body. Another possible mechanism is altered local growth factor gene expression.
Dr. Fenton’s laboratory has identified five diverse endocrine disruptors that cause persistent delays in mammary gland development, alter lactational development, and lead to a number
of other adverse effects. Delayed development leads to longer windows of sensitivity, i.e.,
TEBs that are more susceptible to toxic exposures are present for longer periods of time.
Girls in the U.S. are beginning breast development earlier (as young as 6 to 8 years old)
resulting in an extended window of sensitivity to environmental exposures and heightened
risk of breast cancer later in life.
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DR. MARY WARD:
TOO MUCH OF A GOOD THING? NITRATE FROM FERTILIZERS AND
CANCER