BETHESDA MD—While it’s important that researchers continue to search for gene variations that could increase risk for breast cancer, mapping out the environmental factors that contribute to the disease may be a greater challenge. The interplay of lifestyle and the environment, along with the sheer amount of chemicals and contaminants a woman can be exposed to over her lifetime, makes the environmental side of the equation truly daunting.

The Chemical Dangers

Early life environmental exposures can have a lifelong impact on breast development and function, explained Suzanne Fenton, PhD, at a symposium on the campuses of NIH this spring on women’s health and the environment. A researcher in the NIEHS National Toxicology Program, Fenton and her lab focus on women whose breast cancer has no easily identifiable familial link.

“Twenty-seven percent of all women are diagnosed with breast cancer. However, breast cancer is not the number one cause of cancer death in women. That belongs to lung cancer. Breast cancer ranks number two at 15%,” Fenton stated. “That’s because we’ve done a good job at treating breast cancer but our goal is also to prevent it.” That means knowing what chemicals affect breast health, how they affect it, and when during women’s development are they most susceptible to exposure.

Chemicals in the environment that disrupt hormone levels and interfere with natural hormones are called endocrine disrupting compounds. EDCs can interfere with the synthesis, secretion, transport, binding, or elimination of natural hormones in the body that are responsible for the maintenance of homeostasis. “For the last 40 years, labs have been funded to look at exposures and breast cancer risk,” Fenton said. “Billions of dollars have been spent globally to investigate this.”

Researchers have looked at circulating chemical levels of women recently diagnosed with breast cancer, at potential exposures to chemicals applied to fields and lawns, and at occupational exposures that are correlated with breast cancer. The result is a handful of strong links and many remaining questions.

DDT and dioxins are two of what Fenton describes as “gold medal” chemicals—because the evidence of their link to breast cancer being so strong. In examining DDT, researchers looked at women who were 14 years of age or older during the years prior to 1931. “There was a protective effect for those women, because DDT wasn’t in the environment. The women who were a bit younger had a 4-fold increase of breast cancer risk. The people who were four-to-seven years old during this peak of DDT use had an almost 10-fold risk with an 11-fold risk for those younger than four.” Similar results were seen with dioxin—an environmental pollutant that is a chemical byproduct of manufacturing.

Critical Periods of Development

But exposure is not the only variable. Another is when, during her development, a woman has been exposed. Researchers have focused on when women are most susceptible to chemical exposure and when a toxin can do the most damage. Fenton identified three critical periods of development, when exposure can lead to long-lasting health impacts.

The first is in-vitro. If a mother is exposed to a harmful chemical when pregnant, there can be a dramatic impact on the fetus. “Development is a highly integrated process,” Fenton declared. “During the nine months that it’s developing, a baby forms all of the organs it will need for the next 80 years of its life. This rapid growth leaves many opportunities for lesions, promotion of altered cells, and abnormalities to occur.

“Mammary gland outgrowth happens before birth. Altered developmental programming has shown to a significant health outcome, as has altered pubertal development in appropriate gender-specific characteristics.” For example, in rat experiments, a rat fetus exposed to an antiandrogen can result in the connection to the nipple not being ablated before birth, leading to a male rat with a functional mammary gland.

The second critical period is puberty. For eight to 13-year old girls, it’s a period of exponential growth, and a time that researchers know that mammary glands are particularly sensitive to chemical carcinogens. In pubertal exposures, precocious development can occur—when puberty happens earlier than expected—which could lead to further sensitivity to chemical carcinogens.

“We actually have an epidemic of precocious puberty in girls in the US,” Fenton noted. “It’s caused pediatricians over the last couple of years to kind of rewrite the book on what precocious puberty is in girls. We thought it was abnormal at eight or nine years old to have [stage two breast development]. It’s not abnormal anymore.”

The third critical period of development is lobular development during pregnancy. “You can affect lactation. You can affect the ability to provide milk and the length of lactation, which can lead to offspring mortality,” Fenton stated. This can have lasting impact on multiple generations. In rat studies, those rats whose lactation was affected by chemical exposure had offspring that were malnourished and dramatically underweight.

“Even in a third generation, we saw dramatic decreases in weight gain in the pups. This is because the mammary glands were underdeveloped at the time they were bred.”

The Knowledge Gaps

There are approximately 85,000 chemicals that are approved for commercial use. Of those only 2% have been tested for their health impacts. “In 2007, Silent Spring Institute did an analysis of those that have been tested and found that 216 chemicals have been found to cause mammary tumors in at least one rodent bioassay,” Fenton said.

“We’re clearly not identifying chemicals that affect breast cancer risk very well,” she declared. “One likely reason is that some of the assays that have traditionally been used don’t contain the periods of developmental sensitivity.”

To help fix that problem the National Toxicology Program is incorporating critical windows into their studies. “We’re using mammary gland whole-mounts in evaluation of all the chemicals that may have some sort of EDC-type effect.” 

However, the knowledge-gap is not limited to which chemicals are harmful, but also in understanding of breast development. The rise of precocious puberty might mean that these girls are subjected to longer periods of chemical sensitivity. “[Even when] girls begin breast development early, their breast development ends with the timing of menses. But the timing of menses hasn’t changed over time, while the time of breast development has. If their breasts are beginning to develop early and taking longer to develop, the important structures in their breasts are available for a second hit from the environment,” Fenton said. “We really need to better understand this sensitivity.”

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