Blood Matters

by Masha Gessen

  As framed by the genetic counselors and the BRCA community, the oophorectomy problem went something like this: If you do not choose surgery, there is a roughly one-in-two probability that you will develop ovarian cancer, which is likely to kill you; if you choose surgery, there is a near certainty that you will not develop the cancer. The doubters among us reframed the problem in terms of the risk of other diseases and decreased quality of life—issues that simply were not as salient to the proponents of surgery.

  Kahneman and Tversky identified a range of heuristics—shortcuts in decision making that people have a habit of using. One of them is the “availability heuristic,” which means simply that a familiar experience is recalled and imagined more easily than, say, an abstract example, and influences decision making to a far greater extent as a result. For most of the women living with BRCA mutations, the familiar experience was watching their mothers, aunts, cousins, sisters, or grandmothers die of cancer. I interviewed a twenty-two-year-old woman who had been beating down the doors of surgeons in her town in Michigan asking them for a preventive mastectomy and oophorectomy. Two refused out of hand, citing her age, and one told her to come back in a year and tell him whether she still felt she wanted the surgery. From her perspective, it was an outrageous, and outrageously unfair, example of medical paternalism. After all, if she had come asking for a breast enlargement, she would not have been sent away; in fact, even if she had come asking for a sex reassignment, she probably would have been able to find someone to remove her breasts and ovaries and chase that with shots of testosterone. At the same time, even as I interviewed her by instant messenger, I probed for ways to tell her to wait, to enjoy her sex life while she had her ovaries and breasts, to have children and nurse them, and to rejoice in being so young that by the time her risks really kicked in, there might be a cure. I clearly was not the first person to reach for these arguments, and, just as clearly, it would be no use. She had seen her grandmother die after struggling with both ovarian and breast cancers for nineteen years. She had seen her mother live through a debilitating course of treatment at the age of thirty-four and again at forty-two. What drove her was not even so much a fear of death as a fear of cancer as a way of life—her family’s way of life.

  She so wanted to avoid continuing the family legacy that she was certain she would not want to have children who were biologically her own if they risked inheriting the mutation. The joys of sex and motherhood were vivid and easily available experiences for me but for her, they were things she would not miss if she never experienced them—and she might have been unable to enjoy them anyway, if she was consigned to living with the constant sense of doom.

  I spent hours talking on the phone with a fifty-two-year-old public-health educator in Portland, Oregon. Nancy Prouser was quite certain that she decided to have a preventive mastectomy because she had watched her mother die of breast cancer at fifty-eight. The fact was, though, that Nancy had inherited her BRCA2 mutation from her father, who had successfully battled breast cancer at seventy-six and was still alive eleven years later (about 1 to 2 percent of breast cancers are diagnosed in men, and it seems that many of these may be caused by the BRCA2 mutation). Nancy had the mastectomy with implant reconstruction, and an oophorectomy, and she became a walking consciousness-raising program on genetic mutations. In addition to running a program training clinicians to do breast exams, she lectured on genetic mutations and met with women who were referred to her by genetic counselors. She told me she had “gone into the bathroom at Starbucks to let a woman see and touch my reconstruction.” She was a convincing advertisement for preventive surgery—at her age she would otherwise be more likely than not to have developed one of the cancers—and she was disarmingly frank about the huge blow her body image had sustained. When I asked her about the loss of libido, she laughed: “I’m glad you reminded me! I have none. I forgot.” She had not been trying to hide her loss: It was simply outside the frame.

  My own availability heuristic, clearly, stemmed from the vividness of my mother’s death from breast cancer and the remote memory of my great-aunt Eugenia’s death from ovarian cancer. I had been fourteen when she died. I was aware of her diagnosis, and I was even involved in some of the caretaking, making runs from one end of the wintery city to the other to deliver a jar of beluga caviar that, I think, was supposed to help with the depleting aftereffects of chemo. I accompanied her to the hospital after weekend visits at home a couple of times, and the sight of the cancer center in southern Moscow, a huge gray concrete eyesore that seemed to swallow people whole, still fills me with dread. But I had been shielded from watching her deterioration and death; I recalled her illness as a taxing routine rather than a disaster. It simply was not as scary. And twenty-two years later, as I struggled with my decision, I learned that a woman I knew and respected a great deal had been diagnosed with ovarian cancer at twenty-one. She was now seventy. My own unrepresentative, skewed, utterly unscientific sample seemed fated to calm me and make me hesitate even as virtually everyone else told me to proceed to get my ovaries removed—whether or not I was asking for advice.

  An old and dear friend, who was diagnosed with breast cancer at thirty-six and soon opted for both a mastectomy and an oophorectomy, wrote to tell me I should do the same thing. A friend’s sister, whom I had never met, also wrote, telling me of her experience battling advanced breast cancer in her early forties and suggesting I consider having an oophorectomy, as she had. And, incredibly, a New York City breast surgeon I called to schedule an interview for this book began to advocate for an oophorectomy for me during our first phone conversation.

  In his Nobel lecture on “bounded rationality,” Kahneman explained his theory that people have two systems for making decisions: System 1, which is intuitive and immediate, and System 2, which corrects it.

  System 1 involves what he called “natural assessments,” which come easily to mind. They include similarity: People immediately think of situations that remind them of the current one—as women with the mutation tend to recall their mothers’ suffering and, often, death. It helped me to realize that I was talking not only to women who came from cancer families but also to doctors who came from cancer practices. My own doctor, for example, told me that doctors believed breast cancer hit the best and the healthiest. This was when I was fishing for reassurance: Surely I had improved my chances by being fit—a veritable gym freak—and eating well. She shot me down with the story of a woman who had had it all: good health and a good mind, great friends and a wonderful family, and had broken her doctors’ hearts by wasting away from breast cancer in a few short months. In fact, there is some evidence for the idea that exercise and a low-fat diet help keep genetic cancer at bay—but my doctor was exposing her own heuristic: The tragic story of that one patient simply stuck out in her memory more than other, more predictable breast cancer stories.

  This went to another of Kahneman’s “natural assessments”: what he called “affective valence.” Researchers of risk perceptions have long noted that people tend to fear a horrible death from, say, cancer, far more than a death from heart disease, which kills more Americans than does any other condition. Cancer has a greater “affective valence” than heart disease: It is scarier.

  Kahneman also observed that people are not very good at estimating probability. They try, but they have a clear tendency to overestimate the frequency of events that are easy to recall. He compared the way people deal with probabilities to the way they assess physical attributes such as distance. He used the example of a mountain in the distance. The human mind knows that the blurrier the mountain’s contours, the farther the mountain is. This is the heuristic. But on a foggy day, the contours will appear even blurrier, and on a very clear day they may be unusually sharp. A person will tend to overestimate the distance to the mountain on a foggy day and underestimate it on a clear day. This is the bias.

  For women terrified of breast cancer, all days have a way of being foggy. Studies have consistently
shown that American women think their risk of breast cancer is higher than it actually is—even when, as in cases of familial cancer, it is in fact very high. I knew I was doing this, too: Being told that I had as high as an 87 percent chance of developing breast cancer in my lifetime sounded an awful lot like being told that I would certainly develop breast cancer. Ovarian cancer, once again, was a different matter: Here the lifetime risk was in the 40-to-50 percent range.

  What people do with fifty-fifty risk is a question that has long fascinated scholars of decision making. Kahneman and Tversky based their famous Prospect Theory on a study of fifty-fifty gambles. They concluded that most people will reject a gamble with even odds of winning and losing—unless the possible win was twice as big as the possible loss. This is exactly what my newfound community of mutants was doing: They were engaging in what economists call “risk-averse” behavior by cutting out their ovaries, thereby opting out of the fifty-fifty lottery.

  Meanwhile, what I had done was overanalyze the decision-making processes of other women in order to delay making my own. But I had promised my editor and readers at Slate that I would come to a decision at the end of my research. The editor might even have said I should not feel obligated to keep the promise—but prolonging the limbo would have defeated the purpose of going public. I wrote:

  But I have to make the decisions. So, here they are. I plan to get a bilateral preventive mastectomy with immediate DIEP flap reconstruction as soon as my daughter is weaned, possibly as early as this coming autumn. I am not going to get a preventive oophorectomy, at least until I am 40, and will aim to avoid getting one at all, which means staying up-to-date on early-detection research and forcing my physician to do so as well. This means that for the rest of my life I will bear the physical marks of my mutation and will have to stay obsessively on top of medical research and my own health. This is the sort of thing that eventually happens to most people—but for me, like so many other things, it has to happen earlier.

  I wrote that in May 2004. Then, secretly, I decided to give myself some time to get used to my decision—or not.

  Chapter 6

  The Father of Hereditary Cancers

  BACK IN THE 1960S and 1970s, members of a particular extended family in Green Bay, Wisconsin, used to spend virtually every weekend together. There were eleven siblings—five sisters and six brothers—and they, like their parents, tended to have a lot of children and not a lot of money. So gathering at one or another sibling’s house to hang out and drink was what they did for entertainment. The kids came along and were generally left to their own devices. This turned out to be a recipe for creating community: The kids formed a group that would hold together for decades, perhaps for the rest of their lives. As it happened, the cousins of that generation were mostly girls—about fifteen of them around the same age, all born in the late 1950s or early 1960s: Sheila, Karen, Donna, and a dozen more.

  In the late 1960s three of the five sisters were diagnosed with breast cancer. All three survived their first bouts, but all succumbed to a recurrence by the early 1990s. Sheila’s mother died first. A fourth sister died of pancreatic cancer at the age of fifty-two, a few years later. “They were all in their thirties, and they were all having cancer together,” Sheila remembered years later. She was twelve when her mother died.

  Sometime in the early 1970s—no one remembers quite when—there was a family meeting at one of the remaining siblings’ houses. A doctor from Madison, Wisconsin, wanted all the women and girls of menstruating age to give blood. He explained that there seemed to be something going on in the family, something about everyone having cancer. That somehow made it official: Three sisters having breast cancer at the same time was not a freak accident but a fact of medicine, perhaps of fate. The cousins, who were all in high school by then, started talking about cancer obsessively. They dubbed themselves “cancerphobes.” They assumed they would die of cancer before they reached their early forties, which seemed a long, long way away but still a freaky prospect. Some of them even joked they would have their breasts cut off to keep the cancer at bay. This, though, was morbid humor, not a suggestion anyone would have considered seriously.

  Whoever came to draw the family’s blood in the 1970s seems to have left no traces at the University of Wisconsin at Madison, where he may have been a graduate student. His idea of studying only the females in the family was not particularly sophisticated—in fact, it was plain wrong from the point of view of genetics—but the very concept of identifying a family that seemed to have cancer running through it was forward-thinking at the time. It was only in 1966 that another young Midwestern doctor, Henry T. Lynch, had, to the derision of his colleagues, suggested that cancers might be heritable.

  Lynch had taken a bit of a circuitous route in his career, serving first in the U.S. Navy, then completing his course work toward a Ph.D. in genetics before finally going to medical school. In 1961, his first year as a resident, at St. Mary’s Hospital in Evansville, Indiana, Lynch met a patient coming out of D.T.s and conscientiously tried to interview him about his reasons for drinking. The patient’s story proved unexpectedly coherent and compelling: Everyone in his family had died of cancer, he said, and he expected the same fate. The dread drove him to drink. As a former geneticist and future oncologist, Lynch was fascinated. He took down the patient’s history. Then he took down a number of other family histories. Gradually, the idea that cancer could run in families went from a crazy intuition to a scientific theory. Somewhere along the way, Lynch discovered that back at the turn of the century a Michigan pathologist named Aldred Scott Warthin had described a family that had cancer running through it—“cancer excess” was the term used in the literature. Warthin had stumbled upon this knowledge in much the same way as Lynch: The pathologist’s seamstress, who had grown severely depressed, divulged her family’s devastating medical history at the doctor’s prodding. The seamstress later succumbed to the family cancer, which in retrospect appears to have been a particularly virulent form of colorectal cancer now known as hereditary nonpolyposis colorectal cancer, or, simply, Lynch syndrome—so named for Dr. Henry Lynch, who in 1966 first described two Midwestern clans as having “cancer family syndrome.” As it happened, he and Warthin had stumbled not just upon similar families but upon families whose members suffered from the same syndrome, which caused them to develop colorectal cancer at an early age—forty-four, on average.

  There was more than a seven-decade gap between Warthin’s original research and Lynch’s pioneering paper. Another thirty years would pass before the genetic—and therefore sometimes familial—nature of cancer would become not only accepted fact but a cornerstone of research in oncology and genetics. In the intervening decades, Lynch would become so accustomed to staying ahead of the curve that the fact of his own scholarly eminence seemed to evade him. Not only was he the first person to describe familial cancer, Lynch also seems to have been one of the first doctors to float the idea of preventive surgery—prophylactic mastectomies and oophorectomies—in the 1980s. “They thought I was crazy,” he told me when I asked him about his colleagues’ reaction. Later he also suggested prophylactic colectomies—the removal of the stomach—for patients who hailed from families riddled with stomach cancer. What did his colleagues think this time? “They thought I was crazy,” he repeated, without so much as a chuckle.

  By the time I interviewed him, in the fall of 2005, Lynch had written more than a hundred papers on “cancer family syndrome.” I once read the abstracts in one sitting, which yielded a wildly speeded-up version of the history of the science, and of Lynch’s own evolution. In the 1960s and 1970s he had doggedly chased genetic clues, without much success. He first brought up the idea of prophylactic surgery in a 1977 paper—it seems, out of an exasperation bordering on desperation: There were people dying of cancer—young people predictably dying of cancer—and there was nothing he or his colleagues could do about it. More to the point, he seemed to grow convinced that there was nothing his col
leagues wanted to do about it.

  In 1988, when he had been writing about hereditary cancer for over twenty years, Lynch used an article in a medical journal to attack his colleagues for failing to diagnose the syndrome Warthin had first described nearly a hundred years earlier. The problem was that physicians failed to ask patients about their families, wrote Lynch. Two years later Lynch complained in the journal Cancer that doctors were failing to educate themselves about hereditary cancers. In the early 1990s he seemed to use every opportunity, in any journal, to call on his colleagues finally to learn to take down patients’ family histories. Gradually, he grew belligerent, albeit in a mild, Midwestern, doctorly sort of way. “Despite more than two decades of documentation in the literature, many physicians fail to recognize the clinical features of these syndromes,” he wrote in Diseases of the Colon and Rectum in 1993. Lynch’s campaign to educate, cajole, and occasionally browbeat physicians into being aware of hereditary cancer culminated in 1998, when he agreed to serve as an expert witness, testifying against a doctor at a malpractice trial initiated by a family of a twenty-year-old woman who died of a Lynch syndrome cancer that had not been properly diagnosed despite the mother’s attempts to draw doctors’ attention to the family’s history of cancer. He then described the medical case, the misdiagnosis, and the trial in an article in Diseases of the Colon and Rectum. Genetic mutations connected with many of the cancers Lynch had spent his life studying—colorectal, breast, and ovarian—had already been identified, and now the doctor was really mad. “The question, ‘Is cancer hereditary?’ has been answered beyond any doubt,” he wrote in the journal Seminars in Oncology in 1999. “Have clinicians acted on the importance of hereditary factors in cancer so that this knowledge might be translated into patient benefit? Data showing that 59 percent of patients... still die of metastatic colorectal cancer suggest that the answer is no.”