Radical

introduction

Of all the things to look at while poison is being pumped into your body, the Pacific Ocean is a pretty good option. The first day I walked into a sixth-floor chemotherapy infusion center in Santa Monica, California, I claimed a pleather recliner in front of a tall window facing due west. I could see Catalina Island just to the south, its sloping hills rising up from the water.

For more than a month, I had been mired in the vicious limbo familiar to most newly diagnosed cancer patients. I was crippled with anxiety about the malignant tumors growing inside me and filled with dread over the assault on my body that would soon begin. It’s a strange thing to wait for something terrible to happen when the mechanics of it are entirely unfamiliar. Somehow, I had never known a breast cancer patient. There were women in the outer reaches of my social and professional orbits who had suffered from or died of the disease. But I had never watched it up close. I was in an inhospitable country I did not know and had never visited. I had crossed over into what Susan Sontag called “the kingdom of the sick.”

“Plug me in and turn it up,” I told a nurse as she screwed a long line of clear tubing into the catheter jutting out from beneath my upper right arm. She smiled and checked Facebook on her iPhone in between changing the bags of liquid that ran from an IV pole through the tubing and into my body. The nurse also used her phone to track how long it took for the liquid to run in, a bell-tower ring marking the end of one drug and the beginning of another. The normalcy of the sound reminded me that, while I was undergoing probably the most important event in my life, I was not particularly special and neither was my disease. Aside from the fact that I was relatively young, I was an unremarkable patient with a common disease, one of about three hundred thousand American women diagnosed with breast cancer in 2014.

While breast cancer is common, its influence on American culture and the scientific community is not. There are symbols and awareness campaigns for scores of causes, but none so recognizable as the pink ribbon in October. Celebrities get diseases all the time, but most Americans would struggle to recite the names of famous people who have suffered from them. Yet for every generation, there is a list of well-known breast cancer patients who told the world about their disease: Betty Ford, Nancy Reagan, Olivia Newton-John, Nina Simone, Linda McCartney, Sheryl Crow, Melissa Etheridge, Elizabeth Edwards, Robin Roberts, Julia Louis-Dreyfus.

In addition to being the most public of all the cancers, carcinoma of the breast may be the most thoroughly studied malignancy in human history. The U.S. National Institutes of Health spends more on breast cancer research than on any other cancer type. The American Cancer Society awards more grants to study breast cancer than any other type of the disease. Along with private spending, funds earmarked for breast cancer research total more than one billion dollars every year. This flood of money has made breast cancer a proving ground for advanced scientific research into the biology and genetics of all cancers and the methods devised to eradicate them. As I type this sentence, 1,823 federally registered breast cancer clinical trials are actively recruiting patients.

On the whole, enduring treatment for breast cancer is easier today than it has ever been, with effective smaller surgeries, less-toxic treatments and reliable drugs that blunt side effects and pain. The breast cancer mortality rate is 35 percent lower today than it was in 1990, and it’s dropping steadily, by about 1 to 2 percent per year. We are curing more patients than ever.

And yet, about one-third of all women diagnosed with early-stage invasive breast cancer will eventually see their disease recur or become metastatic. Breast cancer still kills some forty thousand American women every year.

This sobering statistic is a testament to the cleverness of the disease and its ever-growing list of known variations. The malady we call breast cancer is, in reality, a broad category of diseases, each with its own risk profile and sensitivity to drugs. This relatively recent revelation has birthed an oncological race to tailor treatments (and, increasingly, diagnoses) to groups and individuals and apply treatments with greater and greater precision. But scientific progress in breast cancer has been, by any measure, frustratingly slow and incremental. This is not unique to breast cancer. Rather than a straight line toward better and better care, cancer science in general is more like a road up a mountain that’s full of switchbacks and blind corners. The story of breast cancer in America is a story of great successes but also many wrong turns. Things work in the lab and fail in patients. Assumptions about the disease that scientists once held as unassailable facts seem ludicrous in retrospect.

Our inability to end the scourge of breast cancer, though, isn’t just about the disease’s complexity or the slow pace of science. It’s also rooted in where our focus has been for the past half century. It’s now clear that, in many senses, we have been having the wrong conversations about breast cancer. Screening mammograms are helpful to some women, but they fail to detect some lethal breast cancers; sometimes they catch cancers that are not life-threatening but are treated anyway. Breast cancer awareness is at an all-time high. But despite the attention, there has been no successful large-scale effort to learn what causes breast cancer beyond the small percentage of cases tied to hereditary genetic mutations and the identification of risk factors so ubiquitous among American women that they are virtually useless as warnings. Doctors do not know how or precisely why breast cancer spreads, nor do they know how to kill it off once it does. We have spent relatively few research dollars trying to answer these questions. Despite the races, ribbons and scientific breakthroughs, women are just as confused and frightened as ever.

It’s also now clear that in addition to failing to cure many breast cancer patients, treatments women relied on and suffered through for generations were needlessly harsh. After decades of aggressive surgery, chemotherapy and radiation, an approach known as de-escalation is now in vogue, with doctors and scientists studying whether it might be safe for certain women to skip some of these common treatments on the way to good health. Mastectomies, which surgeons once believed could remove the threat of breast cancer at its source, are becoming a last resort for patients. It is now possible to imagine a future in which women with the most aggressive forms of breast cancer might be able to safely avoid surgery altogether. Pharmaceutical companies that make breast cancer drugs are largely focused on a single goal—to replace conventional chemotherapy, a treatment that has been the gold standard for more than seventy years, with targeted and gentler drugs.

As a breast cancer patient in 2014 and 2015, I had the old and the new. In addition to chemotherapy, I had a double mastectomy, surgical removal of twenty-two lymph nodes under my arm, five weeks of daily radiation treatment and a full year of targeted intravenous drug therapy. There was little talk of doing less. At thirty-five and with no family history of breast cancer, the odds that I would be diagnosed with an aggressive form of the disease that had already spread to my lymph nodes were so long that they barely registered on any chart. Even my doctors were scared. I was shocked to learn the news and terrified of what it could mean, of course. But during my 372 days as a breast cancer patient, I realized that while I had been extremely unlucky to get a disease that required a sickening, painful and disfiguring course of treatment, I was also clearly very fortunate. If I had been diagnosed with the same disease a decade earlier, before a groundbreaking breast cancer drug became available to the market for patients like me, it’s very likely I would have died within a few years. If I had been diagnosed even a year earlier, when my breast cancer was likely present but still undetected, I would have had a different, and possibly less effective, course of treatment. I was lucky in other ways too. I happened to live in Los Angeles, which, in addition to being a world capital of breast-augmentation surgery, is ground zero for research into the type of breast cancer that struck me so unexpectedly.

Less than halfway through my treatment, a pathology report transformed my prognosis from grim to excellent. Drugs and techniques allowed me to avoid side effects that were once hallmarks of breast cancer treatment. I worked throughout my chemotherapy and finished with a full head of hair. A few months after my chemotherapy and surgery and just three days after my final radiation treatment, I started a new job with an employer who had no idea I was a cancer patient.

Despite the familiar archetype of a breast cancer patient who battles her disease, I never felt like I was at war. In fact, there seemed to be very little I could do to participate in my own care. I merely submitted to a largely effective regimen that was the result of decades of trial and error.

Still, I had mental whiplash. My own experience had been, in almost all senses, diametrically opposed to the brand of breast cancer I had learned about through popular media’s portrayal of the experience. Before I was diagnosed, in addition to watching tragic breast cancer stories depicted in movies and on television shows, I had even written about the scourge as a reporter for Time magazine, parsing new guidelines about mammography screening and the impact Angelina Jolie’s double mastectomy might have on other women. But I came to realize that the disease I thought I knew was a mirage. Even though my cancer was aggressive and already spreading when I met the oncologist who directed my care, she said my type was her “favorite” because it was so treatable. At the same time, I learned that breast cancer is a more formidable foe than the races, ribbons and culture around it would have us believe.

This is a book about those contradictions—the triumphs and defeats. It’s also about the power of women and what it’s like to benefit and suffer as the result of being a woman. It’s an attempt to explain how we have understood and tried to tame breast cancer throughout history and about what that history, with its twists and turns and misconceptions, says about our society and a disease inextricably tied to the concept of motherhood. This is also a book about America’s particular brand of medicine, bigger and more expensive than care available anywhere else in the world, for better and for worse.

When I told Larry Norton, Memorial Sloan Kettering’s top breast cancer doctor, that I was writing a cultural and scientific history of breast cancer in America, he said, “That’s not a book. That’s an eight-volume set.” Fair enough. This is not an encyclopedia of breast cancer, but through the people, places and science presented here, I hope to deepen understanding of a disease so common that to know something about it is to know something about humanity itself.

No names or personal details of anyone depicted in this book have been altered. There are no composite characters, and no timelines have been tweaked for narrative purposes. Quotes from doctor visits and interviews were recorded on tape or, in a handful of instances, documented in contemporaneous notes. To the best of my abilities as a reporter, this is a true story about a disease that touches nearly everyone in America, the doctors and researchers who work against it, and the women caught in the middle.

1

seek and ye shall find

It got to the point where Diana Petitti had to turn her cell phone off just to get some peace. Reporters had been calling every hour, it seemed, and each one had an urgent question that couldn’t wait. Thanksgiving had been a bust, ruined by the news that Petitti would soon be grilled by a congressional committee. Larry King Live wanted to do a segment and no one could see how that would turn out well.

Petitti had known her work would draw a lot of attention, some of it negative. But death threats? Who could have expected those? You should die, said one e-mail message. I hope you die, said another. The threats rattled Petitti, but she wasn’t scared. Not exactly. She was, more than anything, confused. “It was totally bewildering to me,” she said. “Why all the emotion?”

Petitti isn’t a person prone to emotion. She’s a math geek. She loves the way numbers ground issues, the way they bring clarity to chaos. A few years back, some homes in Petitti’s gated Arizona community were burglarized. Residents were terrified. “People were saying we were in the midst of a crime epidemic,” said Petitti. But what did the numbers say? She went to look. Petitti downloaded crime statistics from the previous three years, plotted them on graphs and sent the data to the community’s homeowners’ association. There was no crime wave. Petitti couldn’t have been more satisfied. “Numbers are comforting,” she said, “because they’re real.”

Petitti earned good grades and got into Harvard Medical School. But after she finished her residency in internal medicine, she realized the work didn’t suit her. “I had more of a fascination with the science of medicine than the aspect where you actually take care of people,” she said. A mentor recommended Petitti take some time away from the bedside and join the Epidemic Intelligence Service at the Centers for Disease Control, a program whose officers collect data and investigate disease patterns in order to shape public health policy. Petitti had found her calling. “I just loved epidemiology,” she said. “Everything about disease causation, data and information.” Epidemiology is the study of how and why diseases occur in populations. Rather than looking through microscopes, epidemiologists analyze statistical patterns and trends for answers.

A few years after her two-year stint at the CDC, Petitti took a job at the University of California, San Francisco, where she taught epidemiology and conducted research. It was the 1980s and the crack epidemic was ravaging many American cities, including Oakland, just across San Francisco Bay. Petitti’s work helped demonstrate a link between Oakland’s growing crack problem and the troubling increase in low-birth-weight babies born in the county. The numbers brought the drug problem into focus and helped local leaders fight for more funds to combat it. It was thrilling. “Just sitting around and analyzing data was not what I wanted to do,” said Petitti. “I wanted to be closer to the ability to take data and turn it into action.”

In 1993, Petitti walked away from her tenured university job to work for Kaiser Permanente, a health system known for designing protocols and health interventions around cold, hard numbers. “Well before people saw the value of data for the sake of data, they were linking data and making it part of their decision-making,” Petitti said. At Kaiser, Petitti published studies on everything from diabetes to contraception, leveraging data gathered from Kaiser’s large patient population to help set policies for doctors and administrators. She even put her obsession with numbers and data to work in long form, publishing a book called Meta-Analysis, Decision Analysis, and Cost-Effectiveness Analysis: Methods for Quantitative Synthesis in Medicine in 1994.

The book, which was reissued in 1999, made a splash in the small world of epidemiology, and in 2004 Petitti landed a coveted spot on the U.S. Preventive Services Task Force. The government-funded body evaluates the effectiveness of tests and preventive treatments and makes recommendations to improve health and save lives. The recommendations are not binding, but insurers often use them to set coverage policies. There was no compensation to sit on the task force and the workload was crushing, but Petitti wanted in. The task force was prestigious, powerful, and, until 2009, the year Petitti started getting death threats, almost universally respected by medical professionals and the public.

The idea of looking for breast cancer before it could be seen or felt started with the cervix. In the late 1920s, physician George Papanicolaou found that by scraping a few cells from the opening of a woman’s uterus and examining them under a microscope, he could detect early signs of cervical cancer. Back then, the disease was particularly deadly, usually found only after it had spread. Papanicolaou’s test, known as a Pap smear, allowed doctors to find and treat cervical cancer early and caused the U.S. death rate from the disease to eventually fall by nearly two-thirds.

If Papanicolaou’s strategy of looking for rogue cells before they grew into threatening tumors worked for cervical cancer, why not breast cancer, which killed far more women? Out of fear or ignorance, until the twentieth century, women often did not seek treatment for breast cancer until their tumors had grown so large they were visible to the naked eye or, worse, had broken through the skin to form ulcerating wounds. By that point, the disease, in most cases, had also spread to vital organs and become fatal. But by the 1950s, early detection of breast cancer had become a public-health mantra. Various organizations urged women to monitor their breasts for signs of cancer, with slogans like “Delay kills!” Pamphlets produced by the American Cancer Society advised women to perform self-exams and tell their doctors if they detected lumps or other abnormalities. Some literature included illustrations of tombstones. The message was clear: Look for early breast cancer and live. Ignore the threat and die. Unfortunately, it wasn’t that simple. In postwar America, doctors were surgically removing breast tumors earlier than they had in the past but seemingly still not early enough. Women were dying of breast cancer at nearly the same rate as before the public-awareness campaign spread across the country.

Technology offered a possible solution. X-ray machines, invented in the 1890s, were widely used to confirm diagnoses of breast cancer made through touch. Maybe, just maybe, they could be used to find breast cancers even before they could be felt.

A New York–based health-insurance company launched America’s first large-scale breast cancer–screening trial in 1963 using a type of x-ray technology known as mammography. (One of the trial’s leaders was a doctor named Philip Strax, whose wife had died of breast cancer in her thirties.) Headquartered in New York City, the program used mammography to provide breast cancer screening to some thirty thousand women aged forty to sixty-four, comparing outcomes to a similar-size group that had not been screened.

In 1971, trial organizers published a paper in the Journal of the American Medical Association that appeared to support the theory that screening mammography could save lives. Between 1963 and 1969, thirty-one women in the screening-trial group had died of breast cancer; in the control group, there were fifty-two breast cancer deaths. In reporting the data, the New York researchers wrote that more follow-up was needed to produce definitive conclusions but that the early results were “encouraging” and grounds for “cautious optimism” about the benefits of screening mammography. Hardly anyone seemed to notice the authors’ observation that “the entire difference in mortality between the study and control groups is concentrated among those women who were aged 50 and 59 years at time of death.”

In 1973, on the heels of the New York trial, the American Cancer Society and the National Cancer Institute launched an even larger screening program. Rather than study whether widespread mammography screening would reduce the number of annual deaths from breast cancer, the program sought to demonstrate that widespread screening was possible. That it would benefit women was assumed. (Unlike the New York study, which compared outcomes for screened and unscreened women, the 1973 screening program did not include a control group.) Between 1973 and 1980, some 280,000 women aged thirty-five to seventy-four were screened for breast cancer at twenty-nine locations across the United States. While the screening program was under way, and amid concerns that the radiation delivered through mammography might actually increase the rate of breast cancer, the National Institutes of Health convened a panel of experts to take a second look at the New York trial data. The panel concluded that mammography screening could reduce deaths in women older than fifty but said it “found no convincing justification for routine mammographic screening for women under 50 years of age.” Again, the caveat was ignored.

Meanwhile, scientists outside the United States were launching their own trials. The most significant were in Canada and Sweden. A Canadian study involving some 90,000 women began in 1980. In Sweden, researchers launched four large trials between 1976 and 1982 involving 283,000 women in five different locations. In all of these trials, the data proved that screening mammography detected more cancers than would have been detected without screening. But the increase in detection didn’t always translate into saved lives. As in the New York trial, not all women benefited equally. The Canadian study found that there was no benefit from screening for women aged forty to forty-nine, and even for women older than fifty, the benefit was unclear. The Canadian study has been reviewed repeatedly and interpreted in various ways, but the conclusion after twenty-five years of follow-up was that screening had no impact on mortality for women aged forty to fifty-nine. Two of the Swedish studies that stratified data by age indicated that after eleven and nine years of follow-up, only women aged fifty and older in one trial and aged fifty-five and older in the other saw their risk of dying from breast cancer go down if they were screened. The results of the other Swedish trials found that screening saved lives, but the effect was less pronounced for women under age fifty. The benefits of screening were real, but they had to be understood in a context that was more complicated than researchers had imagined.

Back in America, after two decades of widespread mammography, it was too late for nuance. Unlike some European countries’ more centralized health systems, America’s breast cancer–screening program was not a program at all. Getting American women to visit the doctor for breast x-rays relied on public campaigns that were intentionally simplistic and easy to understand. “Early detection saves lives” was basic, clear and convincing. Although there was little evidence that screening had a significant impact on breast cancer deaths in women younger than fifty, breast cancer was common enough among fortysomething women that mammography was offered to them anyway. Getting annual mammograms beginning at age forty became a rite of passage for U.S. women. The conversation over when women should begin annual breast cancer screening persisted, but mostly among medical-statistics experts like Diana Petitti.

Many doctors who treated breast cancer patients supported the use of annual mammography beginning at forty. However, a vocal group of epidemiologists maintained that annual breast cancer screening helped fewer women than most people believed and obscured the downsides of mammography, which included radiation exposure and unnecessary testing and treatment. Women, meanwhile, didn’t know what to believe, so in 1997 the National Institutes of Health assembled another panel to review all the existing evidence on mammography and hear testimony from experts over a three-day conference in Washington, DC. The twelve-member panel was largely composed of statisticians and medical professionals who did not treat breast cancer patients. The chair was an epidemiologist from Johns Hopkins. Breast cancer was the second leading cause of death for American women in their forties. Perhaps the panel could settle once and for all whether screening mammography should be performed on an annual basis for women in this age group.

In a blockbuster finding, ten members of the panel said the benefits of screening mammography for women aged forty to forty-nine were not supported by evidence. Women who had been dutifully getting their mammograms every year were furious. Radiologists who made their living reading mammograms were in an uproar. The American Cancer Society, which had previously recommended women forty to forty-nine get mammograms every one to two years, revised its guidelines—but in the opposite direction, telling women annual screening was best. Even politicians piled on. Less than two weeks after the NIH panel report, the Senate voted ninety-eight to zero on a resolution urging the National Cancer Institute to ignore the panel’s recommendation. President Bill Clinton, whose mother had died of breast cancer, said he supported annual mammography for women in their forties and called on insurance companies to cover the test. Rather than settling the matter, the NIH panel had merely proved that mammography was one of the most contentious topics in modern medicine.

So when Diana Petitti and her colleagues on the U.S. Preventive Services Task Force started looking at mammogram data again in 2008, they knew they were wading into choppy, if familiar, waters. Mammography had become something of a religion, with pink-ribbon reminders seemingly everywhere and mobile mammography vans parked in grocery-store parking lots across the country. To question the logic of fortysomething American women getting annual mammograms was to question faith itself.

More than ever, the pump was primed for outrage. In the summer of 2009, as the task force conducted its analysis, the country was consumed by a fight over whether to enact a sweeping federal overhaul of the American health-care system. (The law had a provision stating that plans funded or subsidized by the government had to cover services recommended by the task force.) The tenor of the debate in America’s living rooms and in Washington, DC, reached a nadir in August when members of Congress went home for a recess and were met by angry constituents and protesters. Voters packed town-hall events and shouted down lawmakers accustomed to sparsely attended meet-and-greets. Democrats on Capitol Hill promised that health-care reform would protect consumers and slow the growth in health-care spending that threatened to gobble up nearly one-fifth of the country’s gross domestic product. Republican critics, meanwhile, said the reform plan was misguided at best and anti-American at worst, akin to a “government takeover of health care.” Some warned the plan would lead to “rationing” of treatment and “death panels” that would allow government bean counters to decide which lives were worth saving.