Breasts (21 page)

Last year, I purchased an inexpensive couch from IKEA for the basement. One of the reasons I turned to IKEA is because, I, flameretardant reporter, had heard IKEA’s claim that it was no longer using brominated compounds. I was feeling smug. Then Stapleton
invited me to send her a small chunk from several foam items for a furniture biopsy. (You know we’re living in a strange world when we have to biopsy our furniture.) I cleaved off one-inch cubes from the couch and several random cushions I had around the house and shipped them to Duke.

The cushions came back clean, but Stapleton found that my couch contains a flame-retardant called 1,3-dichloroisopropyl phosphate, better known as “tris,” or TDCPP. This was one of two notorious flame-retardants used in children’s pajamas in the 1970s, until scientists linked the chemicals to DNA mutations. Public outcry forced clothing manufacturers to stop using them. Most of the research at that time was done on brominated tris, while the type in my couch is chlorinated tris. The theory goes that the chlorinated version breaks down more easily in the environment but is more volatile, meaning that more of it escapes the foam. It probably acts in similar ways to brominated tris in the human body. The U.S. Consumer Product Safety Commission classifies TDCPP as a probable human carcinogen, and the EPA considers it a moderate cancer hazard. In 2011, California added tris to its list of carcinogens under Proposition 65.

The first time Stapleton’s mass spectrometry machine identified tris, she couldn’t believe it. “At first, I thought, no one could be using this after all the concern in the ‘70s. We were shocked,” she said. But recently, Stapleton has found tris in a lot of IKEA products as well as those made by other companies, including thirty-three of one hundred tested baby products such as nursing pillows and car seats.

IKEA, to be fair, has few options. It does not put these substances in furniture sold in any countries other than the flame-retardant-loving United States and the United Kingdom. Interested
in what IKEA had to say about all of this, I e-mailed Bjorn Frithiof, a chemical specialist in the company’s laws-and-standards department in Sweden. He responded as soon as the sun rose over Småland. He seemed both matter-of-fact and contrite. “IKEA aims to refrain from the use of chemicals and substances that could potentially be harmful to people and the environment,” Frithiof wrote. “IKEA is currently phasing out all flame retardants of the chlorinated tris type from our products. This work is well on its way.” In a later e-mail, he said the company would replace tris with “an organophosphorous compound which gets incorporated into the polymer matrix of the foam filling. It is a bit early to say if this solution will be the dominant one for our products.”

There’s nothing great about organophosphates, which can also persist in the environment. But if IKEA can figure out how to bind the chemicals to the foam, that would help. It would mean the stuff wouldn’t waft out and work its way into our breast tissues every time we plunk down on the couch.

As my flame-retardant adventures made clear, there’s only so much an informed consumer can do. A better solution would be a regulatory one. California should get rid of its outdated flammability standards. Congress needs to update its chemical laws so these substances can be tested for health effects before they come to market. Many scientists and activists and even some regulators advocate taking a precautionary approach to chemicals that exhibit the big trifecta of concern: persistence, toxicity, and easy transportability.

“If you know it’s persistent, bio-accumulative, and toxic, it will be a problem,” Linda Birnbaum of the National Institute of Environmental Health Sciences had stated flatly. “Since we know, why would we use them? Do we really need these chemicals or are there alternatives?” she’d asked. “The problem,” she’d continued,
“is the term
precaution
has gotten a bad rap internationally. People think it means uncertainty. There’s always uncertainty, but there’s also information. What we should do is act in the presence of information and not require certainty. It’s not the same thing as acting in absence of all information.”

But don’t hold your breath for regulatory changes anytime soon. Several bills to reform California’s flammability standard have failed, much to the disappointment of Arlene Blum, a chemist who first published her findings on the hazards of pajama tris more than thirty years ago and who now runs the Berkeley-based Green Policy Science Institute. Blum led the first American expedition to climb Annapurna and walked two thousand miles across the Himalayas; she said both were easier than fighting the chemical industry.

BREAST-FEEDING IS AN ECOLOGICAL ACT, CONNECTING OUR BODIES
to the world in a complex web of give-and-take. The permeability of breasts allowed us to make great advances. Their estrogen sensitivity allowed us to reach puberty at optimal times. When our early ancestors migrated and settled in river and coastal areas, omega-3–rich diets turned their breast milk into gold, and our brains grew. We recruited, harvested, and bred specialized bacteria for our milk; we collected molecules from the world and from our bodies to manufacture novel sugar and fats to protect our babies. Our special lowprotein milk kept us growing slowly, so we could have the longest childhoods on earth and learn everything we could.

Our brains grew so well that eventually we learned how to change the world’s ecology. We couldn’t possibly have guessed that we were changing our breast milk as well. Our
nouveau crème
no longer serves us as well as it once did. Ironically and tragically, as
breast milk once propelled our evolution, now it may be impeding it by conveying toxins and quite possibly contributing to infertility and brain and body impairments. For many decades, the formula companies have tried to mimic breast milk, but it is breast milk that now may be approximating formula. That is decidedly depressing.

In 2004, the United Nations implemented the Stockholm Convention on Persistent Organic Pollutants (POPs), whereby 162 countries agreed to ban or severely restrict twenty-one of the worst persistent organic pollutants, the world’s most egregious chemical offenders. Most are pesticides, but several are PBDEs, along with PFCs, dioxin, and PCBs, all the top-billed breast-milk additives.

The United States has not ratified the treaty.

Brave new world: A world or realm of radically transformed existence, especially one in which technological progress has both positive and negative results.

—
AMERICAN HERITAGE DICTIONARY

Walking today in an unfamiliar biochemical wilderness, women’s bodies are reacting unpredictably. Breast cancer may very well be one of those reactions.

—JAMES S. OLSON,
Bathsheba’s Breast

I
N THE COURSE OF A LIFETIME, BREASTS MEET MANY FRIENDS
and foes: lovers, babies, ill-fitting undergarments, persistent pollutants, maybe a nipple ring, a baggie of silicone, or a dose of therapeutic radiation. It’s a lot to ask of breasts. Some of them don’t make it to the finish line. Each year in the United States, some seventy-eight thousand women undergo mastectomies of either one or both breasts. Over ten years, that’s enough women to fill the entire city of San Francisco. There are approximately two hundred
thousand cases of breast cancer per year and forty thousand deaths in the United States. Globally, breast cancer is the leading cause of cancer-related death in women. One million women get diagnosed each year, and that number is expected to increase 20 percent by 2020. The global rise will largely be due to longer lifespans, obesity, and better screening. In a word, modernity.

Evolutionarily, though, cancer is a fact of life for multicellular organisms. As the pioneering German pathologist Rudolf Ludwig Karl Virchow discovered in 1855,
“omnis cellula e cellula,”
from one cell grow all cells. We need our cells to divide and replicate. Complex creatures like us would never have seen the sun if it weren’t for the lucky trick of mutations.

Breast cancer has probably been around for as long as there have been breasts. Humans are just about the only free-ranging animal (other than minks) to get it. Domestic pets, if not spayed, get it. Breast tumors can be artificially induced in many other animals in the lab by feeding them strange carcinogens or implanting rogue cells or tissues or messing with their genes.

In some human populations, breast cancer is virtually unknown. Among the Kaingang women in Paraná, Brazil, there is reportedly no breast cancer. Researchers would love to know why. It’s probably a combination of things: the Kaingang women have a shorter life expectancy, they bear many children whom they breast-feed, and they don’t take oral contraceptives or hormone replacement therapy. Also, spending many hours outdoors, they probably get a lot of vitamin D. They probably don’t wear deodorant or underwire bras, both long-held suspects in the breast cancer mystery, but ones that have been reliably exonerated.

Although breast cancer at the rates we know it today is a
modern disease, ancient Egyptian doctors were familiar with it. One papyrus recommends applying a plaster made from cow’s brain and wasp dung to tumors for four days. In the Middle Ages, breast cancer was a known and feared disease. The most advanced treatment at the time was the application of insect feces. Anne of Austria, the mother of King Louis XIV, famously suffered from breast cancer. She died in 1666 after caustic remedies of arsenic paste and a butcherous attempt at surgery (without anesthesia, of course). As barbaric as treatments seem today—slash, burn, and poison—we have it a whole lot better than the king’s mum did.

Bernardino Ramazzini was a Renaissance-era doctor who sought to understand the causes of many diseases, not just their treatments. Born in Capri in 1633, shortly after the teachings of Galileo were banned, he is today considered the father of environmental health. In 1705 he published his life’s work,
De Morbis Artificum Diatriba,
or the Diseases of the Workplace. It’s a lively and, to modern eyes, very amusing work. One of his chapters is titled “Diseases of Cleaners of Privies and Cesspits.” That one makes me appreciate the writer’s life, until I come to “Diseases of Scribes and Notaries.” In it, he writes, “All sedentary workers … suffer from the itch, are a bad colour, and in poor condition.” That one made me get up and go for a hike.

Among the many things that interested Ramazzini were diseases of women, including midwives. In the archaic translation I have, most of the
s’s
look like f’s, rendering such pronouncements as, “Nurfes … are likewife fubject to various Difeafes in the Courfe of fuckling.” Old-language charms aside, Ramazzini astutely noticed that breast cancer was most common in nun
neries. “You’ll scarcely meet with a monastery that has not fresh instances of this cursed [or curfed] plague,” he writes. He admits he does not know the reason, but he calls the breasts and womb the “Fountains of Letchery,” and speculates that it is the “mighty lascivious” among the nuns who will get cancer due to suppression of their sexual drives. Well, he was wrong on the reason, but his observation that nuns were the most vulnerable women remains a critical piece in the modern understanding of this disease.

Women of God did not have a lot of fuckling or suckling going on. What did that mean for the lecherous organs?

Turns out it was a good question. Even W. H. Auden pondered cancer in 1937: “Childless women get it / And men when they retire; / It’s as if there had to be some outlet / For their foiled creative fire.” Eventually, epidemiologists realized it wasn’t foiled creative fire as much as foiled reproduction that caused the trouble. It was childlessness, not celibacy per se, that increased cancer risk. It took centuries to figure out how hormones are made and used in the body, and in fact, we’re still learning. In the nineteenth century, doctors knew that breast tumors were often larger and more aggressive in premenopausal women, and they also figured out that an individual woman’s tumor was sometimes a different size before her period and after. By 1895, a Scottish physician named George Thomas Beatson had experimented with removing the ovaries of cows and pigs. He saw that doing so made their udders shrink, and he speculated that it might make breast tumors shrink as well.

Doubting the conventional wisdom that the nervous system controlled most bodily functions, Beatson presciently observed, “I
am satisfied that in the ovary of the female and the testicle of the male we have organs that send out influences more subtle … and more mysterious than those emanating from the nervous system, but possibly much more potent than the latter for good or ill as regards the nutrition of the body.”

Beatson didn’t know those ovarian emanations were estrogen and progesterone. Nor did he know there were hormone receptors in breast tissue and in many tumors, but he witnessed the hormones in action. In the first woman whose ovaries he removed, her breast tumor retreated and she appeared cured. It seemed miraculous, and news of it made a huge splash. Unfortunately, Beatson also did not know that the body partly compensates for the loss of the ovaries by pumping out estrogen and progesterone-related hormones from elsewhere: fat tissues and the adrenal glands. Four years later, his patient’s cancer returned with a vengeance and she died.

It was only the beginning of a long and disappointing legacy of miracle cures turning out not to be so. But Beatson, like Ramazzini before him, was onto something.

Malcolm Pike, whom we met in chapter 7 tinkering around with pregnancy hormones, is a rare academic hybrid. A mathematician born in South Africa in 1935, he first migrated to Britain in 1956, studying with the famed epidemiologist Richard Doll. Epidemiologists are people who use statistics to study disease, and Doll was their dean. He was the man who established that lung cancer was caused by smoking cigarettes, a conclusion that may seem obvious in retrospect, but was far from it at the time. Arriving in California in 1973, Pike soon fell in with a group of American epidemiologists. By this time, breast cancer rates in the United
States were increasing between 1 and 2 percent a year, a trend that was both surprising and baffling. In 1940, the number of women coming down with invasive breast cancer on an annual basis was 59 out of 100,000. By 1960, even after adjustments for an aging population, it was 72, and by 1990, it was 105 and rising, to the point where the disease now strikes 129 women per 100,000, or 1 out of every 8 women who reach old age. Worldwide, a quarter of all malignancies are breast cancer. The race was on—and still is—to figure out how breasts became so imperiled so fast.

Interestingly, though, Japanese women developed the disease at rates six times lower than Americans. The epidemiologists wanted to know why. They knew it wasn’t due to genes, because once Japanese women migrated to the United States, their daughters’ cancer rates caught up. Was it a virus, or perhaps something else contagious about the American lifestyle or diet?

Pike was familiar with the work of Beatson, and he suspected clues might be found in the difference between American and Japanese women’s reproductive lives. In 1980, he headed to Hiroshima for six months to study the archives of the Atomic Bomb Casualty Commission. In documenting minute details about survivors of the bomb, the commission’s medical records collected excellent data on everything from a woman’s age of menstruation to the number of children she had.

Pike and a colleague found that Japanese women in 1900 first got their periods at age sixteen and a half on average, meaning their ovaries kicked in more than two years later than those of their American counterparts. Their age at motherhood and the number of children they had were similar, but when Pike looked at weight, the data once again stood out. The average menopausal
Japanese woman weighed just 100 pounds; the average American, 145. When Pike analyzed blood samples, he saw that rural Japanese women (and most were rural then) produced only three-fourths as much estrogen as American women.

“We wrote papers explaining that these things, menarche [age at puberty] and weight, might explain half the difference in breast cancer rates between the two countries,” Pike told me during a visit to his office in the Topping Tower of the University of Southern California’s Keck School of Medicine in east LA. As he saw it, American women were simply exposed to more estrogen and progesterone over their lives. Betrayed by their own ovaries and fat cells, these steroidal compounds were somehow causing more cancer.

As early as the 1930s, scientists knew that elevated estrogen levels triggered breast tumors in mice, but it had not yet been proved in humans. In the early days of hormone research, drug companies eyed it and other steroids greedily. Cortisone, for example, mimicking corticosteroids produced in the adrenal glands, was good for treating arthritis. If anyone suspected trouble with estrogen, they looked the other way as it was so promising commercially. Estrogen was known to promote bone density and soften the skin. It could perhaps prevent miscarriage.

Making these steroids in the lab was profitable but complicated. Commercially viable amounts of estrogen could be derived from huge quantities of pregnant horse urine and was first marketed in 1942. It’s still a main ingredient in Premarin, a drug given to menopausal women (more on that later). The first commercially viable quantities of progesterone and testosterone were isolated from wild Mexican yams in the 1940s. Progesterone is a natural hormone
made mostly by the corpus luteum in the ovaries, and later, if pregnancy occurs, by the developing placenta.

The word
hormone
comes from the Greek word meaning “to urge on.” Like other hormones, progesterone travels with its commanding messages through the bloodstream. Among its many powers, it inhibits the release of additional eggs so that we get pregnant only once at a time. During our Pleistocene past, it wouldn’t do for us to be gestating many more than one or two fetuses simultaneously. (This is in contrast to, say, tufted-ear marmosets, who often bear twins and triplets sired by different fathers. The upside to this clever system is that many males in marmoset-land tend to be stellar dads and upstanding citizens, each thinking all babies in the troop are his.)

Progesterone’s uncanny ability to prevent ovulation caught the eye of mid-century drug companies seeking a better source of contraception than condoms,
coitus interruptus,
or the rhythm method. The latter technique requires timing sex to avoid a woman’s fertile days. Although condoned by the Catholic Church, it was known as Vatican roulette for its failure rate. There was clearly a demand for reliable contraception. But medical progesterone had to be given by daily injection or it wasn’t strong enough. A Big Pharma contest was on to find a way to make it potent enough to deliver by mouth.

Chemist Carl Djerassi, considered the father of the pill, describes the quest in his 1992 memoir,
The Pill, Pygmy Chimps and Degas’ Horse.
Born the son of a syphilis-specializing physician in Austria in 1923, he fled the Nazis to arrive in New Jersey as a teenager. By his mid-twenties, he was heading a lab in Mexico City for the pharmaceutical company Syntex. There, in 1951, he successfully fabricated a crystalline progesterone by rearranging some of the
bonds of another synthetic hormone. “Not in our wildest dreams did we imagine that this substance would eventually become the active progestational ingredient of nearly half the oral contraceptives used worldwide,” he wrote. It would become the pill known as Ortho-Novum.

G. D. Searle brought a similar product to the market first, in 1960, under the name Enovid. It was tested on rats, monkeys, and women in Puerto Rico (because many U.S. states banned birth control at the time). By 1970, ten million healthy American women swallowed a little magic pill every day. That’s when Congress, swamped by complaints of the pill’s side effects—everything from nausea to headaches to fatal blood clots—held a series of safety hearings. As the scientists were learning, the ways hormones worked in the body were far more complicated than they appeared. Drug companies had tweaked the original progesterone-only formulation to include estrogen to prevent “breakthrough” bleeding between periods, a discovery that had been made by accident. But hormone doses in the first combination pills had to be high to ensure protection from pregnancy.