Pandora's DNA: Tracing the Breast Cancer Genes Through History, Science, and One Family Tree

by Lizzie Stark

  While breast cancer surgery began with radical mastectomy and went toward lumpectomy, preventive breast surgery began with lumpectomy and advanced toward mastectomy. An 1882 paper by New York surgeon T. Gaillard Thomas on the removal of noncancerous breast tumors without “mutilation of the organ” describes good candidates for the procedure, along with the medical and psychological reasons for the operation. Tumors should be medium sized—in Thomas’s time, that meant about the size of a duck’s egg, though such tumors would be considered huge today. Medically, he wrote, the procedure carried only slight risks and could prevent a smaller tumor from growing dangerously and degenerating from “a benign into a malignant growth.” His untested assumption—that benign lumps can turn into cancerous ones—loomed large in the future of prophylactic mastectomy. He also said that benign tumors could make women really nervous, an anxiety that surgery could ease. Many women with BRCA mutations would find his description of anxious female patients familiar: “I have found that the mere presence of a tumor in the breast usually concentrates upon it the thoughts and attention of the patient, impairs her happiness, and renders her apprehensive, nervous, and often gloomy.” Yes, that sounds familiar, though I might have used a stronger word than “gloomy.” A woman with a tumor, he wrote, spends “a great deal of her time” checking out the lump “and in comparing notes and asking information concerning it of her female acquaintances, and the result of all this is very frequently to engender a state of mental disquietude and wretchedness for the relief of which a resort to extirpation of the tumor is an entirely defensible procedure.” That’s true—only now, thanks to a century of technological advances, we don’t just call female friends; we give ourselves hypochondria by reading too much medical information on the Internet. The lumpectomy of giant benign breast tumors, Thomas argued, had medical and psychological justification. Because such operations were preventive, not curative, they had to cross a higher bar of doing all this without mutilating the patient.

  Thirty-five years later, St. Louis surgeon Willard Bartlett proposed an operation that fit the nonmutilating bill. Like Thomas, he agreed that prophylactic mastectomy had psychological motivations. In a paper advocating mastectomies for women with lumpy breasts, he claimed that “the breast is of such psychic importance to the female patient” that women waited until too late to consult surgeons. “It is the fear of having the breast mutilated that keeps patients away and allows a tumor to run a progressive course,” he wrote. Again, he talked about waiting too long, his words pitting feminine vanity—the psychic importance of breasts—against the curative knowledge of the surgeon. The proposed solution, he thought, was to give women new breasts to satisfy “the psychic element.” To this end, he described a mastectomy very different from Halsted’s. Rather than remove the entire breast, skin and all, Bartlett removed the breast tissue through an incision made at the bottom of the breast where it met the torso—the inframammary fold—and preserved the skin pocket. After cauterizing the interior, he replaced the scooped-out breast tissue with fat moved from the woman’s thigh or butt. Though the details of the surgical techniques have changed and improved over time, the core idea is correct. This sort of operation is considered one of the exemplary standards of breast reconstruction today—a subcutaneous (skin-sparing) mastectomy followed with flap surgery to put your own tissue into your breasts.

  Bartlett didn’t seek to remedy cancer but rather precancer through this operation. He recommended the procedure for women with “chronic fibrocystic mastitis [lumpy breasts], which is generally admitted to be a precancerous condition.” The idea that cystic mastitis—a condition that affects more than half of women at some point in their lives—will inevitably turn into cancer was still a large untested leap, but one that located the vagaries of breast cancer risk physically and palpably in benign tumors. His assumption that lumpy breasts mean cancer risk, and that risk can be carved out of the body, lingered for many decades.

  The faulty belief that lumpy breasts increased a woman’s risk of breast cancer persisted for several reasons. Surgeon Joseph Bloodgood—one of Halsted’s pupils—provided some of the reasoning in his 1931 paper on borderline breast lesions. Cancer and lumpy breasts feel pretty much the same to the hand of the doctor, for example, and reasonable pathologists, examining slides of breast tumors under microscopes, often disagree about whether lumps are benign or cancerous. Rather than attributing this uncertainty to the imprecise science of pathology, which relies on human judgment as well as scientific guidelines, Bloodgood focused on the fact that benign but atypical cells and cancerous cells can look similar. From this he concluded that mastitis and other breast changes “must be looked upon as borderline breast lesions.” This ambiguity—mastitis isn’t cancer but may develop into it—put the surgeon in a rough spot. He had to decide between two crappy alternatives: “The danger of an incomplete operation for cancer and the unnecessary mutilation or removal of the breast for innocent lesions.” Today, of course, thanks to women’s lib, it’s patients who have to make this wrenching decision, not doctors. Faced with uncertainty in 1931, though, Bloodgood thought it was safer for the patient to have the full mastectomy.

  Interestingly, the advance of science caused this headache, Bloodgood argued. Because women knew more about breast lumps—knew that cancer was no longer an automatic death sentence—they began to visit doctors earlier and earlier in their illnesses, so doctors began seeing cancer when it was young and tender and eminently killable. Maybe mastitis was simply baby precancer.

  Preventive skin-sparing mastectomies provided better cosmetic outcomes, but uncertainty about who should have such operations dogged surgeons for decades. By the 1940s, mastectomy for cystic mastitis was on the wane, though when confronted with indefinite biopsy results, many surgeons still opted for the “safer” route of mastectomy. The creation of the silicone implant in the 1960s, which enabled even better reconstruction, drove prophylactic mastectomy to greater popularity, though due to differences in terminology and the patchy way medical advancements become adopted, it’s hard to know how many preventive skin-sparing procedures were done. A mid-1960s survey found that nearly half of all plastic surgeons had performed prophylactic operations, though a 1969 survey found that such procedures accounted for only a small percentage of breast operations.

  Prophylactic mastectomy in the 1970s was marked by more uncertainty than a back-room dice game—uncertainty about who should have the procedure, what constituted breast cancer risk, what mastectomies worked best, and even whether mastectomy worked at all to prevent cancer. Throughout the decade, a debate raged between plastic surgeons about whether and when the procedure was justified. Sure, the operation spared women the physical pain of multiple biopsies and the mental pain of fearing cancer, but did it actually prevent the disease? It’d be more than three decades before the science began to come in. In the meantime, surgeons performed prophylactic mastectomies on women for a whole host of conditions—benign tumors, cystic mastitis, breast pain, fear of cancer, history of biopsies or cancer scares, family history of cancer, and desire to keep breast shape.

  In the meantime, Bloodgood’s observation that the education of women caused doctors to witness more and more ambiguous strains of breast cancer came into full fruition with the widespread introduction of mammography as a screening practice in the 1970s. Greater sensitivity in screening tests doesn’t necessarily correspond to better clinical results. The X-rays picked up stuff that doctors couldn’t feel with their hands, and once they’d discovered a lump, they felt driven to biopsy it just in case. Mammograms can also detect microcalcifications—tiny deposits of minerals scattered throughout the breast that can indicate nascent breast cancer, stage 0 cancer, precancer that is not quite cancer but not quite not-cancer either—and lead to diagnoses like lobular carcinoma in situ (LCIS), clinically ambiguous results that indicate an elevated risk of developing life-threatening disease.

  As mammography became standard in the 1970s, large numbers of w
omen without symptoms underwent screening, which led to a rise in diagnosis of these conditions. Should such breast cancer risk—localized to the cellular level—be treated with mastectomy or not? At the same time, the movement against mastectomy and toward localized surgical solutions was gaining traction, and women demanded more control over medical treatment. This shifted the burden of decision making from surgeons to patients. As French medical researcher Ilana Löwy put it in her book about women and preventive surgery, “In the 1970s, women diagnosed with breast cancer increasingly insisted on their right to participate in decisions about their treatment. The proposal to burden women with the responsibility of making a wrong decision when facing medical uncertainty might have been an unanticipated consequence of this demand.”

  On top of this, it was unclear what sort of mastectomy worked best. A simple mastectomy removed the entire breast en masse but made reconstruction more difficult. Subcutaneous mastectomy, in which surgeons scooped out breast tissue but left the skin, provided better cosmetic results. However, those results depended on having a nice, thick, even flap of skin to cover an implant, which meant balancing cosmetic outcome against the medical result—leaving some breast tissue might improve the flap but compromise the breast-tissue-removing purpose of the operation.

  Finally, there wasn’t much data on whether prophylactic mastectomy worked. Some women experienced complications related to their implants, and a few went on to develop cancer. Plastic surgeon Vincent R. Pennisi, a tireless advocate for prophylactic skin-sparing mastectomy, did a few studies on the procedure. His 1974 survey of 460 plastic surgeons who performed 4,179 such operations over a span of ten to fifteen years found that only twenty-four patients developed breast cancer—about 0.5 percent, and a drastic improvement over the national rate of breast cancer diagnosis. But this survey had problems—surgeons self-selected into it, and it did not have a control group, rendering the data difficult to interpret. Pennisi’s follow-up study five years later found that only two women out of one thousand followed for nine years developed cancer, but this study suffered from similar problems.

  It’s hard to get good data on prophylactic mastectomy. For starters, it doesn’t lend itself to a control group, or to blinding the study from patients or physicians. Given that I’m at high risk for breast cancer, would I really let some researcher randomly assign me to have a mastectomy or keep my breasts? Hell no. The vagaries of risk make forming studies difficult as well. In order to examine whether mastectomy reduces cancer risk, scientists would have to know the starting risk of the women they were studying. And in the 1970s, that wasn’t easy—did cystic mastitis really put women at higher risk for cancer? How much did heredity play into it? The identification of BRCA1 in 1994 would bring these issues into sharper focus, but until then, it was the Wild West.

  In this uncertain era of medicine, my great-aunt Elfrieda urged her daughter Kathy to explore prophylactic mastectomy. At the time, El had terminal ovarian cancer and was busy dying. Suddenly, Kathy says, she’d show up to visit her mother at the hospital, and El would have research on prophylactic mastectomy there. Since she was being treated at the hospital where she’d taught nursing, she had many friends around. Once, when Kathy visited, “all of a sudden there are these two guys in her room,” her mom’s gynecological surgeon and his plastic surgeon colleague who did reconstructive surgery and just “happened to be there.” Kathy knew her mother had arranged for this “accidental” interaction. The surgeons came armed with pictures of the new reconstructive procedure and supposedly wanted Kathy’s opinion because they were about to start teaching the new methods. “I guess she [El] was doing that because she wanted me not to avoid it,” Kathy says. “She was also telling me, ‘It’s different now, they don’t do the Halsted, you can have reconstruction.’ ” While El slipped in and out of comas, Kathy quietly met with her mother’s doctors and obtained referrals to internists and surgeons. She never talked to her mother about it, though. “Since she was suffering so much that last year, I did not want the focus to be on me.”

  El’s final days were grim. The cancer had spread to her spine, and she spent her last eighteen months in the hospital or sitting on the couch at home. Lisa says that for her mother, “it was a great effort to do anything at all.” Her father, Ralph, taught El about football and how to watch football so they could have something to do together. Lisa was in college and had planned to spend a semester abroad in England. Before she left, El told her, “If anything happens to me, I want you to stay and have a good time.” She didn’t want her kids to miss out on anything because of her illness.

  El dealt with her ovarian cancer with black humor, which meant “there was nothing we couldn’t ask her,” Kathy says. For the last two years she wore a wig and navigated in a wheelchair. The daughters watched and helped her. It would take her two hours to get up and get ready, and then she would go out to visit friends or relatives, resting for forty-five minutes after she arrived, visiting for an hour, and then resting for another forty-five minutes to get the strength to go home and go to bed. “But she would do it because she needed to feel like she was a real person and needed to leave the house,” Kathy says. At home, Ralph gave her the garage door opener to press when she needed him if he was out doing yard work. El’s sickness had ups and downs. “It just became normal for her to be very, very ill and then to have a little rebound,” Lisa says. “Every time the phone rang, I wondered whether this was the call.”

  The pain was so excruciating that at one point—as the story goes—El asked one of her sons for marijuana in hopes it might help. As Lisa puts it, “It’s what cancer does to families. They just sort of break down. Other things don’t matter anymore when someone is that ill.” As she died, El charged Kathy with two tasks: to make sure Lisa paid attention to the family legacy as soon as she turned twenty-one, and to find a holiday on which the family would get together so it would survive after her death. Historically, women have provided the social glue that holds a family together—when many women in a family become ill and die, well, families can fall apart. With Lisa, the youngest, halfway through her senior year of college, El’s death came at a transitional moment. “We were at the age when we were trying to be individual,” Kathy says. “It had huge implications for the family, and in some ways we never recovered. Each of us dealt with it in our own way. But the family unit never recovered, and of course that affects my kids.”

  The extended family had broken too. My grandmother Meg had always been competitive with her sister, and she also suffered from periodic bouts of depression and psychosis. Relations between the two sisters had been strained, and at the time El suffered so horribly, my grandmother was dealing with her own drama—a second diagnosis of breast cancer. “Because of the rift, and because of what Meg was going through,” Kathy says, “I had no one.” She couldn’t talk to her father, in part because he was depressed, but also because, Kathy says, “I needed a woman.” Lisa was away at college, and her mom’s best friend was so devastated that she burst into tears while trying to comfort Kathy more than once.

  Amid all of this, and spurred on by her mother’s encouragement, Kathy decided to have a mastectomy for a number of reasons. She’d had her first needle biopsy for something the doctors told her could be in situ cancer at age twenty-one. Since then, she’d had biyearly mammograms and physical breast exams every three months. At age twenty-seven, she’d already had four needle biopsies, and given her family history, the doctors recommended multiple yearly screenings. “The idea of going to have my boobs checked out four times a year—I was afraid I’d become a hobbyist. It felt like it was going to take over my life,” Kathy says. She also had dense breasts that made telling lumps from biopsy scar tissue and normal tissue difficult. “Part of it was just that if I kept having biopsies at this level, I would destroy my skin so much that it might not be possible to have reconstructive surgery,” she tells me. Then, of course, there was the fear—the fear that what had happened to her aunts Trudy an
d Meg and to her dying mother could happen to her. Due to all the cancer in the family, Kathy felt ambivalent about her breasts. “They didn’t seem fun,” she says. “They seemed threatening.” Finally, the way her mother had dealt with the loss of her breasts made Kathy believe she’d be able to bear the pain. Growing up, she says, her mother radiated this attitude of “look at me in my marriage; I am beautiful and feminine, and you will never have the surgery that I have. Life is more important than beauty.”

  Her father offered his total support. “He was there for me,” Kathy says. “He basically said whatever he could do.” But she felt her husband from what she now refers to as her “rehearsal marriage” was absent while her mother was ill, and he thought her plan to have a mastectomy “was crazy and a reaction to my mother dying and that I would regret it the rest of my life.” My mother remembers hearing about Kathy’s plan—she, too, found it extreme at the time, though three years later, after her own breast cancer, she would urge her own sister to have the same procedure.

  Something beyond Kathy pushed her on. “I think there was another fear too. I was afraid that if I didn’t follow through with it, I would never do it. It must be how my son felt when he bungee jumped. There was part of that as well. Like now, even just talking about it now.”

  Twelve male surgeons told Kathy she was having a hysterical reaction to her mother’s illness. “They said no good doctor removes healthy tissue,” Kathy says. The thirteenth agreed to operate.