If we don’t want cancer, we have to coddle our tumor suppressor police. We don’t want them to go on strike, or get sick, or go rogue. This is, tragically, what happens to people who have the mutated breast cancer genes, BRCA1 and BRCA2. Those are technically suppressor genes, acting as DNA repairmen, and they haven’t been working right in some families for thousands of years. One more recent variant of BRCA2 was traced back to a single “founder mutation” in Iceland in the mid-sixteenth century. It’s a heck of a family legacy; around 80 percent of women born with bad BRCA genes will get breast cancer. The ones who don’t get cancer probably have some other lucky genes to help them compensate, or maybe somehow they manage to skate through their developmental windows without any serious carcinogenic exposures. Women with the BRCA genes are much more likely to get cancer if they were born after 1940 than before, a fact attributed to everything from changing reproductive patterns, to body size, to the rise in the use of synthetic chemicals produced after World War II.
BPA appears to turn off some of our blessed suppressor genes and at the same time turn on the bad tumor promoters, the oncogenes. Some of us can resist these events better than others. Remember, the breast is the body’s only organ that still has to do most of its basic construction well after birth. Therein lies some of our problem. With change comes instability. An organ incredibly responsive to cues both outside and inside our body, breasts are too trusting. That quality served them brilliantly in our evolutionary past, but it has not prepared them well for the modern age.
The Russos found that the rats exposed prepubertally were worse off than even the rats exposed in the womb, reinforcing the idea that the time near puberty, when the organ is growing fast, is the most vulnerable, at least to BPA. Their theory is that in order for breasts to form, there are “mammary progenitor cells” that are actively dividing at this time, and they are particularly responsive to hormonal signals. When their genes get messed up during this developmental tumult, they’ll have a harder time warding off disaster later in life.
Jose’s not-very-practical take-home message: “Avoid the exposure of young girls to these compounds.”
IF EARLY PUBERTY IS, AS WRITER SANDRA STEINGRABER PUTS IT, an “ecological disorder,” what’s a mother to do? Is it possible to keep Annabel on the childhood farm a little longer? Larry Kushi, a BCERC scientist and associate director of research at Kaiser Permanente, points to childhood diet as one area over which parents can exert some control. In recent experiments with adolescent rats, a high-fat diet led to inflammation, and later, cancer, in mammary glands. Kushi encourages more whole grains, more vegetables, and less meat. Kushi, the son of macrobiotic food entrepreneurs, is also a fan of tofu, which appears to have some preventative effects as far as early breast budding.
I have to admit, Annabel is not a huge fan of tofu. Or of whole wheat. She’s part of the macaroni-and-cheese generation. I recently heard that children who watch “average” amounts of television will see five thousand commercials, more than half of which are about processed food. The “ad pyramid,” dominated by fats, oils, and sweets, is exactly the opposite of the traditional government-recommended nutrition pyramid (now it’s a nutrition plate). Fortyfour percent of TV ads pitch sugary foods, while 2 percent pitch fruits or vegetables. It gives the term boob-tube a whole new meaning.
But some societal trends are pushing back. The public school system in Boulder recently stopped serving chicken nuggets. It replaced chocolate milk with organic low-fat milk. The cafeteria also switched to using organic, locally grown produce, all under the able tutelage of Ann Cooper, an Alice Waters protégée known as the “Renegade Lunch Lady.” She started a Colorado-based nonprofit called Lunch Lessons to improve school lunches for the sake of things like health and attention spans. “We’re done with Day-Glo orange cheese,” she pronounced, earning my lifelong devotion.
Hoping Cooper would offer some other inspiration for my home cooking, I visited her at the school’s district headquarters. Wearing a white chef’s tunic, she ushered me into a cramped office filled with books. Was Cooper aware of the early puberty or breast cancer research? Not at all. But she’s happy to add it to her arsenal of reasons to improve lunches for eight thousand public school children. It didn’t surprise her that hormone-mimicking chemicals might be messing with our girls’ bodies. Cooper, it turns out, is a DES daughter. She told me she’d been badly affected by the drug her mother took in pregnancy.
Under Cooper’s direction, a gleaming salad bar now holds center stage in the school cafeteria. Back in the kitchen, the spaghetti and tortillas are whole wheat. The rice is brown. Hamburgers are served just once a month. I want to throw my arms around her in gratitude. Surprisingly, though, she said some parents are complaining about the loss of chocolate milk from the lunchroom. If Boulder Valley, with its culture of Buddhist triathletes, can’t improve kids’ diets, I don’t know who can.
I’ve also changed some things in our own house. From our body burden experiments, I’ve learned to avoid scented products when possible. No air fresheners for us. No floral dryer sheets. No lavender shampoos. I don’t want to make it sound like I’m a total killjoy, because that’s not my style. We still use the occasional plastic straw and we still have plastic toys. I refuse to say to my children, Step away from the Lego. I still buy cheese in plastic because I’m not about to buy a cow.
In an ideal, childhood-preserving world, I would banish TV and avoid taking my kids to the grocery store with its eye-level barrage of snack temptations. So I’m working on that, but I’m not an all-or-nothing kind of person. I’m cutting down on canned beverages and foods. I could take a cue from Copenhagen’s Aksglaede, who no longer washes her hair or uses sunscreen with products containing parabens or phthalates. (It’s easier to be a savvy shopper in Denmark because that country requires labeling.) I now often pack my kids’ lunches and snacks in thick glass containers and cloth sacks. This at times makes me feel virtuous, but more often than not, it feels like an exercise in futility. The food, after all, comes right out of a plastic carrot bag, bread bag, or cracker box. Even if I had the patience and fortitude to strap on a bonnet and grow the food myself, my local water supply carries a load of contraceptive and other hormonally active compounds.
In fact, the whole prospect of trying to individually safeguard one’s family from silent endocrine disruptors feels like a folly, because it can’t be done in any meaningful way until the government and chemical companies change the way they test, manufacture, and market these substances.
We can only eat so much quinoa out of a paper bag.
• 7 •
THE PREGNANCY PARADOX
The beginning is glorious … suddenly they begin to grow … breasts fantastic tender apricot breasts, then charming plucky firm tangerines, and then, just as you were on the verge of peaches, oranges, grapefruits, cantaloupes, God knows what other blue ribbon county-fair specimens, your stomach starts to grow and the other fruits are suddenly irrelevant because they’re outdistanced by an honest-to-God Watermelon.
— NORA EPHRON,
Heartburn
OFTEN, WHEN A WOMAN BECOMES PREGNANT, SHE FIRST knows it by her breasts. They hurt and tingle as if someone just plugged them into a sound amp. And they grow, of course, doubling their weight and size, and the nipples enlarge and grow darker. I rejoiced in the physical changes of pregnancy. I loved my new growing shape, even liked the maternity clothes, except the granny underwear. I didn’t gain much weight in pregnancy and it took me a while to start “showing.” I was so thrilled when the first person who didn’t know I was pregnant asked if I was. “I can just tell,” she said knowingly.
I also enjoyed the bigger bustline, no doubt about it. Those new breasts cracked me up. It was as though I’d borrowed someone else’s. I was partly right; the breasts weren’t really the same. They weren’t just my old breasts on hormones. Those county-fair specimens were in fact different breasts. It’s something I’ve said before, but it’s so cool I�
��ll say it again: these are the only organ in the body that is not fully grown by adulthood. Breasts grow up when there’s a baby cooking one story down.
Biologically, this is interesting. Medically, it’s an epiphany. For at least several decades, researchers have known that the changes wrought by pregnancy protect those breasts from cancer. Lately, they’ve been wondering when we might be able to imitate, bottle, and patent that protection.
That quest has long motivated Irma and Jose Russo, whom we met in the last chapter, and Malcolm Pike, an epidemiologist at University of Southern California and Memorial Sloan Kettering Cancer Center. They and others have been studying the protective effects of hormones on tumors and thinking of ways to mimic pregnancy, because, as Pike puts it, “making every girl have a baby at fifteen is just not going to happen.” Perhaps the most we can ask for is a sort of medically induced hysterical pregnancy, or an immaculate conception minus the baby. If every young woman could just experience a simulated blast of pregnancy juice, she would be protected for life against breast cancer. Sure, she might have some strange cravings (and sore breasts) for a time, but well worth it. Pregnancy hormones, it turns out, are shockingly good cancer-preventing drugs, at least if you get the hit early in your reproductive life.
Here’s what we know: a woman who has her first child before age twenty has about half the lifetime risk of breast cancer as a nonmother or a mother who waits until her thirties to have children.
These statistics have played out in my family as in so many others. My grandmothers and great-grandmothers were unusually early adapters to the modern notion of having children late. My mother’s mother, Carolyn, wanted to be a judge. She graduated from Stanford Law School in 1926. She joked that there were so few women around, she could have a different date every night. Unlike most women of her generation, she was willing and able to put off marriage and children. After Stanford, she shared a law office in San Francisco with her stepfather. In her late twenties, she fell in love and married a young lawyer from Buffalo, New York. At twentyeight, she had her first child, and then two more.
My other grandmother, Florence, a Chicagoan, married long after her compass was pointing firmly to spinsterhood. She fell in love late, with a tall Virginian, and had her first child at age thirtythree. These days that age seems perfectly normal, but in the 1930s the average age of first-time motherhood was 23.7. Before 1960, nearly one-third of American females had their first child before reaching age twenty. The pill changed all that. Since 1970, the percentage of women having their first children at age thirty-five or later has risen eightfold.
Carolyn, my lawyer grandmother, was first diagnosed with breast cancer in her sixties. She recovered, but the disease struck back in her eighties and ultimately killed her. Florence wasn’t so lucky; just before her sixty-first birthday, she died of ovarian cancer, which is often linked genetically to breast cancer. Her mother had died of breast cancer in her fifties, and she had given birth to her first child at age twenty-nine. My mother, in contrast, had her first child, my brother, when she was eighteen, in 1950, well before effective birth control would become widely available to unmarried women. She didn’t get breast or ovarian cancer, but she did succumb to a blood cancer in her sixties. Lately I’ve been wondering if her reproductive history might actually have helped her. Her early pregnancy interrupted her career, but it might have extended her life.
Knowing that I and so many of my peers had our first children well into our thirties, I’m both unsettled and intrigued by the power of pregnancy. The age at first pregnancy is now considered one of the most salient risk factors for breast cancer. In the life cycle of breasts, pregnancy is their defining get-out-of-jail card. If you draw it early, you’ve done as nature intended, and you’re rewarded. If you arrive late or not at all, nature is less forgiving, for reasons scientists are now uncovering.
SO WHAT’S SO GREAT ABOUT PREGNANCY, FROM A BREAST’S PERspective? Aside from the happy boost in bra sizes, the answers aren’t clear. The body is flooded with sky-high levels of estrogen, progesterone, and HCG, or human chorionic gonadotropin. This is what dime-store pregnancy tests measure, since HCG levels spike only in pregnancy. Different scientists disagree on exactly what the magic ingredient or combination of ingredients is and what exactly those hormones are doing. Something about pregnancy rebuilds the breast and armors it, by changing the architecture of either the cells or the proteins around them. One leading theory is that when the breast becomes fully mature by the end of pregnancy, its stem cells, which have been quiet, “differentiate” into cancer-resistant, highperformance dairy equipment. Even after weaning, the protection remains. But when the stem cells are waiting around for decades for their dance card, they’re either weaker or just more likely to proliferate into cancer. And in a woman who’s never been pregnant, her breasts remain undifferentiated for life.
“Women are so delicate,” murmured Jose in his thick accent as he explained this to me.
“Yes, we are,” shrugged Irma. “It’s not sexist. It’s our hormones.”
In addition to studying the “window of vulnerability” that occurs around and after puberty, the Russos are also looking at the long cone of protection around pregnancy. Both pathologists, they are expert at picking out minute changes in tissue and cell structure and, in fact, seem to see things others can’t. They first noticed dramatic changes occurring in rats, in which mammary cell changes are more obvious. Just as in people, lab rats that have been pregnant are less likely to get breast cancer. In one experiment, the Russos exposed “virgin” rats to a cancer-causing chemical. Some rats, however, had been primed with pregnancy-level HCG hormones. As the Russos suspected, those rats were the lucky ones. Their cancer cells divided less, their mammary cells shut down estrogen receptors, and they expressed more cancer-fighting genes.
I COULDN’T HELP BUT WONDER IF THE PREGNANCY-AS-PREVENtion evidence might bolster the theory that many breast cancers are environmental in origin. If the breast is being “armored” in pregnancy, it’s being armored against something. The lab experiments use chemical carcinogens to trigger cancer. The mother rats are protected while the virgin rats aren’t. In humans, known genetic factors account for only about 10 percent of all breast cancers. On the one hand, you could argue that delayed childbirth “causes” cancer. But isn’t that because something else is really causing cancer in unprotected tissue? I asked Irma about this.
She cautioned that we really don’t know what causes breast cancer. But, she said, “from about the ages of twelve to thirty-five, from puberty to first pregnancy in many modern women, is a huge window to get exposed to radiation, alcohol, tobacco, phytoestrogens, xenoestrogens, and all the suspected carcinogens accumulating in the breast. If the same woman gets pregnant or gets the right hormones around puberty or a little later, the breast will mature and be more protected.”
When I visited the Russos’ lab in Philadelphia, their collaborator, Colombian scientist Johana Vanegas, showed me what was actually happening to the cells in the presence of pregnancy hormones. The rats’ mammary glands had been removed and then put through a mini-meat-slicer-type contraption. Then the slices had been dyed dark pink and splayed out on small glass slides. I peered into an Olympus stereomicroscope to see some sections taken from rats that had never been pregnant. These “immature” glands looked like purple flower buds painted with a broad watercolor brush. Next I looked at the HCG-fed glands. These looked very different. The buds had transformed into the tiny petal dots of a pointillist painting. The immature glands represented by the watercolor image, at least in a rat, are called “terminal end buds,” and they represent the undifferentiated state of cancer-vulnerable cells. Watercolor buds: bad. Pointillist petals: good.
The Russos say they can see the same thing happening with human breast sections under a microscope, although it’s a controversial observation. They call the smooth never-pregnant glands “lobule type 1” and the late-pregnancy pointillist florets “lobule type 4.” In th
e early and mid stages of pregnancy, you get the inbetween lobule types 2 and 3. The higher the number, the more protected the cells. Among other things, lob 1 has more receptors for estrogen and progesterone, which, as we’ve seen, can be an entrance ramp on the cancer highway. Jose points out that the genomic signatures of the different lobes change dramatically as a woman cycles through pregnancy and beyond. Both full-on pregnancy and just a dose of HCG activate good-cop (tumor suppressor) genes, stop cell growth, and turn on other cancer-fighting genes, presumably for life.
Why for life? Because after pregnancy and lactation, the pointillist petals dissolve and revert to smoother buds, but these lobules tend to remain hardy types 2 and 3, say the Russos. If, as they speculate, cancer originates in lobule type 1, that would explain the protection offered by pregnancy: fewer type-1 lobules, fewer chances of cancer.
I’D HAD A GUT SENSE THAT PREGNANCY WAS CHANGING ME IN profound ways. Those mysterious hormones were bathing me in bliss, altering my core chemistry in a way that would prepare me for parenthood. Although I’d felt some ambivalence about what life would be like after having a baby, I’d wanted a child. I’d suffered a couple of years of miscarriages and failed conception, and now I was thirty-four. I’m sure part of my happiness was pure relief. But now I appreciate the power of the hormones, which seem, in retrospect, to have acted on nearly every cell in my body.
The thought of chemically mimicking this experience for a possible faraway health benefit gives me pause. But for some women, such as those who know they are carriers of breast cancer genes, playing with the ephemera of pregnancy might be worth it.
The Russos have begun testing their patented HCG regimen in eighteen high-risk women who have never been pregnant. The women will take HCG for three months, and then the Russos will compare their before-treatment and after-treatment genes to see if they’ve changed from a “high-risk signature” to a low-risk one. Natural HCG is made by the developing embryo, so the Russos get theirs from a synthetic process. HCG has some bizarre properties, including stimulating plant germination. The hormone has been tipping women off to their pregnancy status since 1530 BC, when Egyptians in the eighteenth dynasty watered seeds with their urine. If sacks of wheat and barley sprouted, a woman knew she must be pregnant. Today, some weight-loss clinics administer HCG because it’s believed to help reduce abdominal fat when combined with a calorie-restricted diet (the better to feed a phantom placenta). MTV reality star JWoWW even sells it on the Internet. She gushes, “While on the HCG diet you will sleep sounder and feel better than you did before!”
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