Breasts (10 page)

In the meantime, no one in her lab drinks out of a plastic bottle.

A COUPLE OF PAT HUNT’S OBSERVATIONS HAVE BIG IMPLICATIONS
for breasts. The first is that diseases like cancer can start in the womb, even in the egg, in its earliest beginnings. The second is that synthetic chemicals that whack out our hormones are popping up in wholly unexpected places, like our grocery receipts. Since her first accidental discovery in the lab, hundreds of other scientists have also studied BPA, wondering, among other things, what it does to how the breast grows and develops.

Numerous studies have confirmed that BPA activates the estrogen receptors on breast cells and can cause cancer cells to replicate in a dish. In addition, BPA has been shown to cause normal breast cells to act like cancer cells, growing invasively when they’re not supposed to. BPA and similar compounds can turn on and
off genes in breast cells in ways that foster cancer. When fetal or young rats are fed BPA, they can be more susceptible to getting cancer later on when they are exposed to other carcinogens. There is something about BPA that alters the way rats’ mammary glands grow and respond to later threats. In other rat experiments, prenatal exposure to low doses of BPA caused lesions in mammary glands. When researchers at Yale fed DES (a very strong estrogen) to some pregnant mice and BPA (a weak estrogen) to others at levels approximating those found in pregnant women, both offsprings’ mammary glands produced more of a protein called EZH2. Higher EZH2 levels are associated with an increased risk of breast cancer in humans. And it didn’t matter much to the glands whether they received the strong or weak estrogen. This was a chilling discovery for those toxicologists still clinging to the ages-old adage that the dose makes the poison.

Cancer isn’t the only concern. There is also some evidence that chemical exposures, delivered very early in life, can alter the way the milk-making structures grow, as well as re-jigger the timing of breast growth during puberty. In industrial countries, human breasts are appearing earlier in childhood (stay tuned for the next chapter), and women in the United States suffer from more problems breast-feeding than women in Africa or South America.

It’s treacherous drawing connections between lab rodents and people, but if our historical DES experience is any guide, the lab data can be telling. Our mammary glands are similar to those of rodents, and we are sensitive to the same hormones. These potent chemical signals are the ancient currency all vertebrates share. Estrogen is the oldest steroid of them all, with our cellular receptors originating over 550 million years ago. Our bodies inherited an eons-old ability to absorb it from our surroundings, even after
we learned how to make it ourselves. We are a modern motif on an ancient device.

Why are our estrogen receptors such disappointing judges of character? Why are they so promiscuous, hooking up with many different kinds of compounds? Two reasons. One is a central theme of this book, so it’s worth saying again: organisms like us are designed to be biologically responsive to the world around us. Scientists call this “phenotypic plasticity.” It means we can tweak our bodies a little bit if it looks like we need to,
regardless of our DNA.
Our hormone receptors are sensors; they are one of the ways we gauge the world. The estrogen receptor, though, is confoundingly catholic in its tastes, more so than the other steroid receptors. Its lock will take any key with a carbon ring structure, and others besides. As bad luck would have it, this structure is the same building block used to make numerous synthetic compounds, including many plastics, solvents, and pesticides.

Our breasts, for better or worse, have more varied and more sensitive hormone receptors than other organs. If anything, their receptors veer toward oversensitivity. They need to sense the environment to store fat and grow at the optimal time and feed an infant in an uncertain world. What might have been handy once upon a time now looks increasingly like a liability.

This leads us to the second reason, which is that our receptors never before had to dance with so many bad actors. In the past, estrogen mimics were mostly plant estrogens, and many of them are weak and possibly even beneficial. Some phytoestrogens block our receptors in a good way. Some studies suggest that high-soy diets, for example, help prevent a recurrence of breast cancer in survivors, as well as delay breast development in girls, perhaps by protecting their cells from their bodies’ more active estrogens. We coevolved
with plant estrogens, and that’s probably why we can metabolize these compounds quickly. We were also exposed to them seasonally and in limited amounts. BPA, on the other hand, comes to us in a daily drip and, notably, reaches us in the womb.

BPA was proved eighty years ago to act as an estrogen. You might wonder, as I did, why on earth, if BPA was known to behave estrogenically, did it go on to become the principle ingredient in ubiquitous polycarbonate plastic, an ingredient known to break down easily and escape into the environment?

The answer to that would be a long and sorry tale about the lack of government oversight, inadequate testing (in fact, virtually nonexistent testing) for hormonal effects in safety studies, and the phenomenal power of the chemical and pharmaceutical industries—à la Big Tobacco—to sow seeds of scientific doubt and maintain a favorable regulatory landscape.

If known estrogenic compounds such as DES and BPA could fly so long under the safety radar, what about the other thousands of chemicals in our world, especially the ones that are not obvious hormone disruptors? How safe are they? In the United States, seven hundred new chemicals come to market each year, joining the eighty-two thousand already in use. Of these eighty-two thousand, only a few hundred have ever been tested for health effects. Despite the thirty-five-year existence of government regulatory agencies and their guiding laws in the United States, including the Toxic Substances Control Act, only five chemicals have ever been banned. DES was still manufactured in this country as recently as 1997. Unlike in Europe, American companies are not required to perform safety studies on chemicals before they introduce them into the marketplace. In fact, they have a strong incentive not to
perform them. In the United States, every chemical is assumed safe until proved guilty. The burden to do that falls on government and university scientists, who don’t have the institutional muscle or resources to keep up. It takes years of work to prove that a chemical causes harm, and a shield of proprietary industrial secrets has kept manufacturers from revealing which chemicals they are even using. These recipes may be private, but they swim in your bloodstream and in mine. Of the 650 top-volume chemicals in use, four billion pounds get released into the American water and air each year. Forty-two billion pounds are made here or imported
each day
for use in products and materials.

The U.S. government does occasionally single out some chemicals for lab-animal testing, and the Environmental Protection Agency has recently finalized new tests for routing out the top suspected endocrine disruptors. The official tests, however, focus on certain well-established endpoints: the liver, the kidney, the genitals, and the brain. “They leave the mammary gland in the trash can,” pointed out Ruthann Rudel, a toxicologist at the Silent Spring Institute, a Massachusetts-based nonprofit that advocates stronger environmental testing.

The mammary gland, once again, occupies a forlorn and forgotten place in science. This is especially disturbing since independent scientists have found that the mammary gland is the
most sensitive organ
to known culprits such as BPA, DDT, and a common weedkiller called atrazine. Banned in Europe but used in the United States to the tune of seventy-five million pounds a year, atrazine is a major contaminant of drinking-water supplies. In the body it appears to increase the activity of aromatase, an enzyme that converts testosterone and other hormones to estrogen. In affected frogs
and fish, scientists are seeing damaged reproductive organs. Rats who are exposed early in life are showing signs of altered mammary gland development and increased incidence of mammary tumors.

The journal
Cancer
reported in 2007 that limited testing (mostly by independent scientists) has so far found 216 chemicals known to cause mammary gland tumors in animal studies. These include chlorinated solvents, products of combustion, pesticides, dyes, radiation, disinfectants, pharmaceuticals, and hormones. Twenty-nine are produced at levels greater than one million pounds per year in the United States. Seventy-three are present in consumer products or in food. Roughly one thousand chemicals have so far been shown to alter animal endocrine systems. These compounds include anti-androgens and thyroid impersonators, not just estrogens. One of Rudel’s projects is to corral various laboratories and agencies to develop standard tests for recognizing damage to the developing mammary gland.

WE’VE GENETICALLY MODIFIED OUR CROPS TO BE ABLE TO PROTECT
them from the ill effects of pesticides, but we haven’t yet figured out how to modify our breasts or livers or brains. Perhaps someday we’ll have GMO breasts along with GMO corn. In the meantime, it’s next to impossible to draw a line between a particular chemical in our lives and a disease or symptom that might show up decades later. When we do notice a problem with a common drug or chemical, it’s because the resulting effects are either very unusual (rare vaginal cancers in DES daughters, mesothelioma in asbestos workers) or very obvious (shortened limbs in children whose mothers took thalidomide to prevent morning sickness).

With DDT, the effects have been more subtle and more varied.
But the eventual catalogue of ills, recounted by Rachel Carson and many others, made the endocrine-disruption hypothesis possible.

A chlorinated hydrocarbon, DDT had a great run during World War II as an insecticide, sparing soldiers from grim deaths by typhus and malaria. After the war, its manufacturers were eager to grease its transition to civilian uses. As Brigadier General James Simmons rhapsodized, “The possibilities of DDT are sufficient to stir the most sluggish imagination. In my opinion, it is the War’s greatest contribution to the future of the world.” It was sprayed from airplanes over fields, suburbs, playgrounds, and country roads. It was aggressively marketed to housewives and farmers alike. By 1950, it was so widely used that 100 percent of houseflies were resistant to it. Still, its use continued unabated, and by the early 1970s, 1.3 trillion pounds had been sprinkled, sprayed, and dusted in the United States. Many adults today remember gleefully running or biking through the fog sprayed by DDT trucks and planes in the 1950s and 1960s.

After dead insects, birds were DDT’s first notable victims. Most famously, the pesticide wiped out populations of bald eagles, peregrine falcons, and brown pelicans because it weakened their eggshells and altered nesting behavior. It wasn’t long before scientists started looking for effects in other animals and humans. They measured it in human blood, umbilical cord blood, and breast milk, and they found associations between high levels of the pesticide and the incidence of diabetes, miscarriage, poor semen quality, shortened duration of lactation, preterm birth, low birth weight, and decreased cognitive skills in children.

DDT and its main breakdown product, DDE, are very difficult to get rid off. Fat-loving, stable molecules, they reside in animal tissues (as well as in soils and streams) and stay there for decades.
Thirty years after the ban, these molecules are still detected in most human blood samples tested by the Centers for Disease Control and Prevention.

Several studies have compared the DDT levels in women with breast cancer to those in women without breast cancer. Nothing remarkable showed up. But then in 2007 researchers looked at blood samples collected from mothers in the 1960s. The younger women, the ones exposed to the most DDT as
girls
(at levels still measurable in their blood because of DDT’s long half-life), had a fivefold increase in breast cancer incidence later in life. The girls who were older than fourteen when DDT was introduced had no increase in the incidence of cancer. For the girls who received their hits in early youth, the blow was much worse. In other words, the timing of the exposure was critical, similar to the effects seen of radiation in bomb survivors and BPA in mice. This study may well help explain why women born after 1940 have much higher levels of breast cancer than women born before. There were simply more chemicals soaking their childhoods.

DDT was just the first in a line of troubling organic pesticides. Next came dieldrin, aldrin, chlordane, heptachlor, hexachlorobenzene, and others. After World War II, our thrumming petroleum and chemical-weapons machinery readjusted beautifully to civilian outlets. Cheap by-products of fossil-fuel production found myriad new uses. Benzene became a building block for BPA, flame-retardants, insecticides, and scores of other formulations. Today we use thirty times more synthetic pesticides than in 1950, nearly nine pounds per person. When Rachel Carson wrote
Silent Spring,
she noted that one out of four Americans would get cancer in their lifetimes. Now, the rate is 1 out of 2.5. An aging population accounts for much of that change, so it helps to look at age-adjusted rates
for specific cancers. When we do, we see that the incidence is notably rising for endocrine-related cancers such as breast, prostate, and thyroid. We now know many chemicals have the potential to cause cancer and much more subtle effects, as we’ll see. It has taken three generations to find out.

Chemical World News
reacted to the publication of
Silent Spring
by calling it “science fiction, to be read in the same way that the TV program, ‘
The Twilight Zone
’ is to be watched.” But the public responded to Rachel Carson, and by the mid-1970s, Congress had passed laws to begin to regulate the chemical industry. In 1972, DDT was banned.

Carson wrote, “If we are going to live so intimately with these chemicals—eating and drinking them, taking them into the very marrow of our bones—we had better know something about their nature and their power.”