Breasts

by Florence Williams

  In the Russos’ trial, the women have noticed getting thicker, luxuriant hair, some weight loss, and a feeling of well-being and energy. “The ladies say they have a glow,” said Irma.

  Down at Texas Tech University Health Sciences Center in El Paso, pathologist Raj Lakshmanaswamy is a fan of using therapeutic estrogen rather than HCG to mimic pregnancy. (I know what you’re thinking: if early puberty is any clue, estrogen is bad for breasts, but the reality is more complicated than this. While estrogenic substances may indeed be bad for the youthful, developing breast and the breast that already has tumors, estrogen has been given a worse rap than it deserves. I’ll talk more about this in chapter 12.) Lakshmanaswamy envisions a hormone patch that women can apply for just three months in their early twenties to protect them from breast cancer. “We’re talking about levels equivalent to the low end of pregnancy levels,” he said. “It shouldn’t cause any problems for that short a time. We’re not there yet, but this is my feeling right now, that it can be done.” Unlike the Russos, he hasn’t patented this idea, saying he’s more interested in basic science.

  In LA, Malcolm Pike’s team is looking at the breast tissue of women who have already received high doses of pregnancy hormones. These women are patients in fertility clinics who are taking mega hormones to help them “hyper-ovulate,” or produce a large number of eggs for in-vitro fertilization. “Does that change their breast?” asked Pike. “We don’t know. You just have to do the hard thing, which is to study women. We do know egg donors have the breast-stimulating equivalent of three months of pregnancy in just one week of taking hormonal drugs. How does it happen and can you mimic it in smaller doses? They get a tremendous biological effect very, very fast. It’s possible it happens in just two to three days. We need to check them again a year or two later and see if the same differentiation is there.”

  A major challenge in developing a fake-pregnancy drug is finding the right dose. “When you’re pregnant, you have astronomical levels of steroids,” Pike continued. “Absolutely astronomical. Before pregnancy, you might have 100 units of estrogen in your blood, and when you’re pregnant, you’d have 10,000 units or more. If I gave you that by mouth, you’d die. So a number of us are fiddling with it. It will still be a long time in the future. It’s the early days yet of chemoprevention.”

  THE PREGNANCY EFFECT SOUNDS LIKE A SLAM DUNK: YOU GET high levels of hormones, you’re protected for life! Except that it’s not a slam dunk. There’s a lot of fine print. For example, the abortion exemption. You might think that if these pregnancy hormones are so great, then women who’ve had abortions are also protected, because they too enjoyed the spiking hormones of early pregnancy. The evidence, though, seems to suggest that this does not happen. Some years ago, a distinguished researcher named Janet Daling published results of a study suggesting that women who got abortions before the age of eighteen were more likely to get breast cancer, not less. A few other studies found similar results. The right wing seized upon this data, gleeful to have another reason to condemn abortion. Pro-life groups even sought legal action requiring that abortion be mentioned as a cause of breast cancer to any woman seeking abortion. Early in the George W. Bush administration, the federal National Cancer Institute’s website proclaimed that abortion could increase a woman’s risk of breast cancer.

  Then in 2003, the National Cancer Institute convened a panel to sort through the evidence. It concluded that abortion did not increase a woman’s risk, and that studies to the contrary were damaged by “recall bias,” one of the notorious bad sisters of scientific method. Here’s how these studies are typically conducted: You interview a bunch of women, say in their fifties, some of whom have had cancer and some of whom haven’t. The catch is that the ones with cancer are much more likely to come clean about past indiscretions. In other words, as Pike described it to me, “abortion gives you breast cancer if you’re Catholic, but doesn’t if you’re not.” It appears the non-cancer Catholics simply lied about past abortions. Ah, the joys of epidemiology! No wonder these things are hard to sort out.

  In any case, no one can claim that abortion protects you from cancer, nor do natural miscarriages. It seems a full-term pregnancy is needed for the breasts to fully differentiate. Which renders the high-dose, short-term faux-pregnancy therapies a big question mark, to say the least.

  …

  AROUND ABOUT THE 1980S, SOME DOCTORS BEGAN NOTICING AN unexpected pattern: young women who had been pregnant in recent years were getting breast cancer. Rather than being protected by pregnancy, some women were experiencing the opposite. These women tended to be relatively older when they had their first child, and they tended to suffer from premenopausal breast cancer. What if the protective effect of pregnancy was just a myth or, at best, a historical relict?

  In the mid-1990s, Pepper Schedin was, like so many other researchers, studying the storied protection offered by pregnancy. Everyone knew the breast goes through massive changes in pregnancy, but Schedin thought it might be worth looking at the massive changes that occur after pregnancy (or for those women who breastfeed their babies, after lactation), when the breast regresses back to a “resting” state. This process is called involution, or the massive loss of cells and structures that were part of the dairy machinery. In fact, 80 percent of the glorious pregnant breast gland simply disappears. Its ability to practically vanish overnight is yet another unique and strange feature of breasts. Schedin thought perhaps this was why mothers might not get breast cancer; perhaps nascent tumors were zapped out during this epic house cleaning.

  She ran some experiments and found that while normal cells were indeed killed during involution, breast cancer cells were, startlingly, promoted. “Oh man, was that a surprise,” she said. Just around that time, Schedin was contacted out of the blue by an old friend who had recently borne twins. The friend, who was in her thirties, had just been diagnosed with metastatic breast cancer. “I thought, huh, that’s strange. It went against everything I’d ever heard. Pregnancy was supposed to be protective. Nobody ever mentioned it wasn’t. So I went back and looked in the literature, and there it was: a small body of work on pregnancy-associated breast cancer, and no one knew why it was happening.”

  As far back as 1880, Samuel Gross, the surgeon subject of the celebrated Thomas Eakins painting Gross Clinic, noted that after pregnancy, breast cancer “was wonderfully rapid and its course excessively malignant.”

  The phone call changed Schedin’s life. She now works in the young woman’s breast cancer program at the University of Colorado’s Anschutz Medical Center in Denver. Her office was decorated with framed photos of mammary gland cells and a giant poster of the well-known U.S. Postal Service breast cancer stamp. On a corner of her desk sat a 1915 microscope that her brother found in a junk shop.

  Over the years she has made some interesting discoveries, most having to do with how the molecules of the breast talk to one another during involution. Remember, the breast gland doesn’t just perch in an empty vacuum. It’s a resident in a busy neighborhood filled with fat, collagen, and extracellular matrix, a rainstorm of proteins, hormones, and other material. Schedin has found that during involution, this matrix orchestrates a type of inflammation. Most of us are familiar with inflammation—it’s what happens when a paper cut gets red and swollen or when we bump into the table and get a bruise. Immune cells rush to the injury and help repair it and battle infection. A similar thing happens to the retreating breast gland after lactation: macrophage immune cells swarm in to help clean the old gland and remodel the remaining tissue.

  The problem is that sometimes our milk ducts have weird little not-quite-normal growths in them. Usually it’s not a big deal, but sometimes these growths, or lesions, break free of the duct for reasons nobody entirely understands, tap into blood veins for nutrients and oxygen, and grow like bananas. Hello, cancer. This jailbreak appears able to happen during involution, promoted by the inflammatory environment. Schedin calls this the “involution hypothesis.” It’
s just a theory, one of several, but she likes it. Older women are more likely to have these precancerous lesions in their ducts (perhaps thanks to their long years of environmental exposures); hence they’re more likely to unleash cancer after their pregnancies.

  So while young mothers may indeed be protected by pregnancy, old mothers are not. In fact, mothers who give birth after thirty have a slightly higher risk of breast cancer than women who never have children. That’s right: if you heard nuns had it bad, older moms have it worse. And the types of cancers these moms get are more aggressive. A study in 2011 found that the more times a woman gives birth, the higher her risk of “triple negative” breast cancer. A cancer subtype making up about 10 to 20 percent of all breast cancers, these tumors do not express receptors for estrogen or progesterone, meaning they are more resistant to treatment and more deadly. (By contrast, postmenopausal breast cancers tend to be slower growing and can often be treated with hormonal therapies.) Women who have never given birth have a 40 percent lower risk of this type of breast cancer.

  For the legion of us who had kids late in the game: bummer. Fortunately, pregnancy-associated breast cancer, called PABC, is still quite rare. In the United States, about 3,500 cases are reported per year, but under the standard definition a cancer has to be diagnosed within one year of pregnancy. Schedin fiercely disputes this definition and says pregnancy-related factors are still very much at work for many years after delivery. She thinks the risk goes up for five and maybe even ten years after pregnancy. “It’s far more common than the stats let on,” she said.

  Sturdy and fit, with shoulder-length brown hair and glasses, she walked me through the eighth-floor lab overlooking east Denver. We passed a bank of freezers calibrated to –80 degrees Celsius (–112 Fahrenheit), the magic temperature for preserving the code of life, the RNA, in tissue samples. The tissue culture room smelled vaguely of cough syrup and sported a photo on the wall of a goofylooking baby wearing a pink hat, below which exhort the words “Find a Cure before I Grow Boobs.” The scientists here know they’re working to help real people, thanks to their partnership with the university hospital and the young women (generally under forty) who proffer their cancer cells for research. In return, the lab tries to come up with therapies that will help these women before another forty years go by in the war against cancer. Schedin called this mission “Bench-to-Bedside.”

  If she’s right and inflammation is causing trouble, Schedin wants to know what happens if you reduce it by taking ibuprofen, or fish oil, or other anti-inflammation substances. She’s setting up a trial to find out. Another translation to the real world Schedin is willing to bet on: new mothers should get screened for breast cancer. Right now. They make up another high-risk group, she said, just like women over fifty or women with a family history of the disease.

  She finds it unfortunate that the pregnancy-as-protective camp dominates much of the field. A street-tough Chicago girl who litters her words with expletives, Pepper is aptly named. “Not everyone agrees with me, but we need to let the science speak for itself,” she said. “Pregnancy-associated breast cancer is too devastating to ignore.” She’s grateful that her work has led her to think of the breast in a whole new way, as a highly responsive organ whose signals get easily crossed. “I consider the gland plastic and poised to respond to signals because it needs to be quick to respond to pregnancy,” she said.

  If the breast needs to be responsive in pregnancy, it’s because it’s preparing for its big-night out, its very raison d’être: breast-feeding. All its 200 million years of evolution and all its individual months and years of construction and signaling and wiring are for this event. Nowhere is the breast more responsive and more conversant and more mind-blowingly intelligent than where there’s an actual baby on tap.

  • 8 •

  WHAT’S FOR DINNER?

  First we nursed our babies; then science told us not to. Now it tells us we were right in the first place. Or were we wrong then but would be right now?

  — MARY MCCARTHY,

  The Group

  IDIDN’T BOTHER TO READ THE SECTIONS IN THE PREGNANCY books about breast-feeding. I was much more concerned about the pain and blood and gore of childbirth. I got stuck on the terrifying bit about pushing a head the size of a bowling ball through what was now bluntly called “the birth canal.” I found that part so colossally distracting that I waved off what the books call the fourth stage of childbirth: lactation. I was a mammal. How hard could it be? I would flip through those sweetly illustrated sections later if I made it through the delivery alive.

  How wrong I was.

  What I didn’t know, what I couldn’t know, was that childbirth ended up being the easy part. It turns out I was a bit of a champ at it. Nurses filed into my room to watch my breathing technique. In between contractions, they talked about real estate. I didn’t need drugs; I didn’t even accept an Advil when it was over. “You’re tough,” said my doctor, shaking his head. My son was beautiful, if a little orange looking. My pride swelled.

  But then came the pain and the blood, and it came from breast-feeding, the part of the deal that was supposed to be all saccharine and drenched with love hormones. The first time Ben latched on was wonderful, a little strange, but the fact that he knew what to do seemed a miracle. His strong little mouth created a vacuum like a particle accelerator. The second time he latched on, it hurt, and the third time, it hurt more. My nipples grew inflamed, then formed canyons of fissures, then bled. They looked mangled. I couldn’t wear a shirt, much less a bra. My mother-inlaw came to visit, and I staggered around the house looking like a crazy bleeding topless person who’d had an unfortunate accident with farm equipment.

  I was doing it all wrong. What I learned the hard way is that neither women nor babies “know” how to breast-feed, despite this enterprise being a fundamental part of our humanity. (To be fair, the babies know more than the mothers. Studies have shown that right after birth they are capable of a heroic “crawl” to the nipple, which might be colored extra dark for their blurry-eyed benefit.) If we human mothers once instinctually knew how to nurse babies, we lost it along with things like the ability to make vitamin C. Through our evolving social context, we learned from each other how to eat foods with vitamin C and how to tickle an infant’s chin so his mouth will open bigger for breast-feeding. Now, though, we have lost the social transmission that came from living in kin groups. We are replacing it with the paid profession known as “lactation consultant.”

  Mine was named Faylene, and she made house calls. Friendly but no-nonsense, she showed me the football hold, the lying-down hold, even the upside-down hold (the baby, not me). She helped me open my son’s mouth wider and stuff more of my areola in it, and she showed me how to gently break the force-of-nature suction with my pinky when it was time to stop. It was bewildering, but I was getting the knack. Then a relative noticed my son was now even more orange hued. He was diagnosed with a condition called breast-milk jaundice, in which some unknown component of my milk was temporarily interfering with the ability of his liver to break down bilirubin. A pediatrician told us that if this weren’t corrected by a twenty-four-hour break from breast milk and immediate application of artificial light to his skin, he would suffer brain damage.

  We fed him formula from a bottle for a day and a night while I tried to pump my engorged breasts. When it was time for our reunion, Ben looked at my nipple like it was a foreign metal object. Faylene told me this is called “nipple confusion.” I called her back for more body contortions and face stuffing to reacquaint Ben with the real deal. We were finally getting everything sorted out on day 10 when I suddenly felt like I was going to die. My temperature spiked to 104 and my right breast turned to red, hot cement. I went to the emergency room. I had mastitis, a blockage or inflammation of a milk duct that triggers a systemic infection. I needed antibiotics, and I needed them fast. I couldn’t help but wonder how humanity had made it this far. What happened to cave women with yellow babies and c
logged ducts and no ER? Breast-feeding may have helped the species evolve, but not before killing off a good percentage of its mothers with what used to be called “milk fever.”

  I would get mastitis three more times that first year. I’m not sure what propelled me to stick it out. Faylene, probably, and a dogged sense of granola-girl duty. But then, once the agony ceased, I found I really liked breast-feeding. In fact, I loved it. Ben and I would settle into our bright-yellow glider at all hours of the day and night. I learned about things that went on along my street at four in the morning that I never imagined. Sometimes I flipped through a magazine or just marveled at my son’s now-porcelain skin. I loved the surges of prolactin, a gentle stoner hormone, and of oxytocin, which, as one writer describes it, produces “slight sleepiness, euphoria, a higher pain threshold, and increased love for the infant.” I loved the lazy intimacy with my son, and the way he panted and flapped his arms with joy when it was time for dinner.