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

by Lizzie Stark

  Meg discovered the lump during a family vacation. My grandpa Roy, a professor of horticulture at the University of Arkansas, often attended a summer professional meeting; he’d bring the family along and they’d make a vacation of it, seeing sights and camping along the way. In 1968 they took one such trip to Davis, California, loading the kids—Cris, Gret, Curt, and Mark, who ranged in age from sixteen (Cris) down to eleven (Mark)—into their white Ford Falcon station wagon. It was an era before seatbelts and bucket seats—the kids took turns riding the hump up front, crowded in the backseat, sometimes atop the cooler, or sprawled out in the way back on top of the luggage. Sometimes they stopped at convenience stores for a treat to have with their sandwiches—a soda and a candy bar for each of them. The car didn’t have air conditioning or a radio, so they started out each day by singing two hymns and often passed the time by singing other songs. Occasionally my grandpa would depress an imaginary button on the dashboard and tell the kids that would send out the wings and make the miles fly by.

  As usual, the family camped their way through Nevada. This trip, they stopped to see the Hoover Dam and celebrated Meg and Roy’s wedding anniversary at a park outside Las Vegas, where Roy gave his wife a pearl ring. That night in bed in the tent, my grandpa remembers, Meg turned to him and said, “Roy, feel this. Do you feel a lump here?” He did. It was about the size of an olive.

  Because they were past the halfway point of the journey, and because Meg had two cousins, both doctors, who lived a couple of hours away from Davis in Reedley, California, the family headed directly there, where one of Meg’s cousins examined her. He told the family to turn around and go back to Fayetteville and even called ahead to Meg’s local doctor to arrange immediate treatment. Roy cancelled his meetings.

  The couple broke the news to the kids that mom was sick and needed to return to her local doctor immediately. It’s unclear whether all the kids learned that “sick” meant “lump in her breast.” Cris remembers, “I’m pretty sure it was Dad who told us, and I think he said they didn’t tell the boys. I’m not sure when they told the boys.” My uncle Mark remembers the car being silent on the way back and that the family stayed overnight at a KOA campground close to a car crash. He remembers seeing “cars mangled up. It was the first time I’d seen a big car wreck like that, and it made a bigger impression on me than anything else on that trip.” Dogged by car trouble, the family drove straight home to Fayetteville, sometimes pulling over to sleep by the side of the road.

  Forty-eight hours after she’d felt the lump, my grandmother visited her doctor, who told her that she probably had cancer and called for exploratory surgery the following day, a psychologically merciless procedure. In those days, in order to avoid the inconvenience of putting a patient under general anesthesia twice, physicians typically put a woman under, biopsied her tumor, and if the results were malignant, removed the breast without waking her up. My grandmother—like so many other women—fell asleep not knowing whether she’d wake up breastless or with a Band-Aid.

  Meg’s first mastectomy was brutal. My aunt Cris called it a “butcher job.” As my uncle Mark puts it, “I had the sense that they just kind of chainsawed her breast off. When she woke up, this was incredibly traumatic for her…. My mom was also a very pretty lady and very proud of her appearance, and this was a very defeminizing experience also, that the medical establishment did this to her without concern for her appearance…. This was very, very hard for her.” She carried anger about the procedure with her for the rest of her life. A few weeks later, Meg began radiation or perhaps chemotherapy treatments in Fort Smith, a fifty-mile drive down a winding mountain road in a hot un-air-conditioned car under extreme emotional pressure. My grandpa’s boss let him take off work to drive her. She required treatments several days a week for several weeks, and they’d return home in time to pick the kids up from school.

  Ten years later, Meg lost her other breast to a second bout of cancer. Like her sister El, Meg was beautiful and vivacious, with a cloud of dark hair cut to the current fashion. She’d suffered from insecurity about her physical attractiveness—especially compared to her sister—for much of her life, and she associated her breasts with her femininity and never got over their loss. My grandpa tells me he tried to reassure Meg, explaining to her, “We can go into a restaurant, and you can sit at a table, and some guy across the room can look at you and say, ‘What a babe,’ and the assessment would be right.” He loved her for who she was, not what she looked like. Showcasing his humor, “I told her more than once, I didn’t realize until about five years after we were married how good looking you were.” He complimented her beauty, explained that he hadn’t married her because of her breasts, that he’d rather she lost her breasts than a leg, and that he loved her, but Meg still struggled. Hearing about this decades later from my grandpa, I could barely keep it together; forty years after her mastectomy, my grandmother’s same emotions would pour from my mouth, and my husband would offer my grandpa’s reassurances in return. Despite the medical advancements that have dramatically changed the nature of mastectomy—the circumstances around our operations could hardly be more different—we had responded to the essential emotion of loss in similar ways. Like Meg and El, I would turn to fashion as a balm for my body fears.

  Five years after Meg’s first breast cancer diagnosis, in 1973, in faraway Rockford, Illinois, her sister began to feel strange. El’s periods became irregular and she spotted between them. She felt full all the time. She gained weight. And her lower intestinal tract seemed angry with her. The doctors couldn’t figure out what was wrong—maybe a partial bowel obstruction? Her symptoms worsened, though she and her husband kept them from the younger children, and years passed.

  In 1977, Lisa spent one of her last summers at home, between her junior and senior years of high school, working as a seamstress at a bridal shop. Her mom had gotten her the job because she used to buy some of her clothes there, and a driven Italian woman ran the place. Lisa had exactly thirty minutes each day for lunch. On one particular day, she used the time to drive to the hospital with her dad to see El as she woke up from what Lisa believed was a hysterectomy. Lisa remembers, “My dad and I are standing in her hospital room, and they wheeled her in, and her doctors and nurses must have been there. And she was coming out of anesthesia and she said, ‘It’s bad, isn’t it?’ ” Lisa felt dumbfounded. “[My mother] was visibly horribly upset, my father was upset, and I had to go back to work. I had to go to the old house where the bridal shop was and realize what was happening. ‘It’s everywhere, isn’t it?’ It was almost like she knew when she came out of it.”

  El had stage IV ovarian cancer that had spread all over her pelvic cavity and into her liver. Over the next two years, she endured more radiation and chemotherapy, spending time in and out of the hospital. By 1978—the same year Meg developed breast cancer for the second time—the cancer had spread to El’s spine, and she had trouble walking. Because El had taught at the hospital where she received her treatment, her hospital room was a lively place—her many friends among the doctors and staff would come by and chat. El spent about eighteen months slipping in and out of comas, but she never lost her characteristic wry humor. On one occasion, after she’d spent three days in a coma, her eyes popped open and she asked the kids, “Does this make me born again?” Once, when she thought the end was near, she asked Lisa and Kathy to clear out her underwear drawer because she thought that would be too painful for her husband. They packed everything up and tossed it. And then, El lived. She needed new underthings, so Kathy tells me, with a smile in her voice, that El asked them to go to her favorite boutique and buy everything again, but in black and red. And they did it. After waking up from another three-day-long coma she entered on Mother’s Day, she told her kids she couldn’t have died that day. She said, “I would never do that to you guys—because then how will I have grandchildren if I die on Mother’s Day?—because you’ll hate Mother’s Day.” In the years before her death, she’d beco
me interested in Kübler-Ross’s five stages of grief (denial, anger, bargaining, depression, acceptance) and would counsel her children about being in this or that stage over her.

  In January of 1979, El died.

  My grandmother, still recovering from treatment for her second breast cancer, was too distraught to attend her sister’s funeral. She’d lost every member of her nuclear family to cancer—her father had succumbed to lymphoma shortly after Trudy’s death, while her mother had passed from uterine cancer at age eighty-five.

  Cancer wasn’t finished with my family. El’s dreadful, lingering death kicked off a slew of horrors. In 1981, the same year my grandparents welcomed their first grandchild—me—into the world, Roy developed colon cancer, initially misdiagnosed as terminal liver cancer, which he survived. In 1985, my grandmother would develop stage III ovarian cancer—a huge psychological blow for someone who had already lived through cancer twice—and a horrific physical ordeal that she survived against all odds. The mortality rate for ovarian cancer hasn’t budged much since 1940—even today, only 44 percent of patients diagnosed with ovarian cancer survive for five years or more.

  In between my grandpa’s colon cancer and my grandma’s ovarian cancer, in 1983, my parents finally took a honeymoon. They’d been married for five years and lived in Dallas, where my dad worked as a tax lawyer. They stashed their eighteen-month-old (me) with my father’s parents and headed to Hawaii for a few days. In an eerie echo of my grandmother’s breast cancer diagnosis, for a long time my father claimed that my mother found the lump on vacation, his memory muddled by time and emotion, this worry conflated with the actual bad news some months later. In fact, my mother had had a routine physical that included a mammogram right before the trip. While she and my father vacationed, the doctor’s office called to explain that the scan had been clean.

  Four months later, my mother found a lump on the front of her right breast while showering and immediately scheduled a doctor’s appointment. Since her recent mammogram had been fine, her doctor suggested they adopt a watch-and-wait approach for a few months and prescribed some vitamins. A few weeks later, with the lump unchanged, she had an uninformative needle biopsy. Then came the surgical biopsy. Thanks to the women’s health movement of the 1970s, my mother did not fall asleep uncertain of whether she’d wake up sans her right one. They woke her up, delivered the unfortunate results, and performed the mastectomy the following day. The verdict—rendered a few weeks short of my mother’s thirty-first birthday—was stage II infiltrating lobular cancer of the right breast. Her tumor had grown from nothing—as indicated by her recent mammogram—to a monstrous four centimeters in only four months. The simple mastectomy removed her entire breast but not the underlying chest muscles, as a now-outdated Halsted would have. Luckily, her biopsied lymph nodes showed no signs of involvement. And thanks to the advancement of medicine, she had her cancer tested for estrogen receptors as well.

  In the 1890s, Scottish surgeon George Beatson had experimented with removing the ovaries, first of sheep and cattle, and then of breast cancer patients, and discovered that ovarian removal could shrink breast tumors. In the 1920s, scientists identified the hormone estrogen, but the big breakthrough wouldn’t come until the late 1950s. Canadian surgeon Charles Huggins discovered that certain hormones could perpetuate the growth of prostate cancer—he would later win a Nobel Prize for his research—and he wondered whether a similar mechanism might be at work in breast cancer. He experimented with the removal of the ovaries and the adrenal glands, which also secrete sex hormones, including estrogen. He found that the removal of these organs beat back cancer—at least temporarily—in 30 to 40 percent of advanced breast cancer patients. At the time, there was no way to tell who was in the group that would benefit; so he urged Chicago chemist Elwood Jensen to look into it, and Jensen did. As it turns out, some breast cancers contain receptors that are stimulated by estrogen, which promotes the cancer’s growth, and some do not. Over time, scientists would discover that certain breast cancers may also express a fondness for progesterone or contain a lot of HER2/neu, a protein that occurs on the surface of some tumors and can promote cancer growth. Soon, therapies targeting these sorts of cancers would come on the market, adding hormone therapy and drugs that target HER2/neu pathways to the modern arsenal of cancer-fighting agents. Breast cancer related to a BRCA1 mutation—as my mother’s cancer was, though of course we did not know it at the time—is more likely to strike younger women and is more likely than non-BRCA breast cancer to be negative for all three receptors.

  At the time of my mother’s cancer, only the estrogen receptor (ER) test was available, and hers came up negative. Many women would consider ER-negative cancer unlucky, because ER-positive cancer provides physicians with an extra weapon against the invader: deprive the beast of the hormones it feeds on and watch it die. My mother chose to view her ER-negative cancer positively; it meant she could take hormones for menopause far down the road without worries about feeding some itinerant cancer cell. She received six chemotherapy treatments and thirty radiation treatments. A few months after her diagnosis, she found a lump in her other breast. The doctors believed the lump to be benign, but she decided to take that breast off prophylactically.

  Though it wasn’t known then, current research shows that most women with cancer in one breast do not benefit from having the remaining breast removed preventively, a procedure known as contralateral prophylactic mastectomy. For women with sporadic (non-hereditary) cancer, several studies show that the risk of developing a second breast cancer in the healthy breast is relatively low—around 3 to 9 percent. In addition, having the second breast removed does not significantly improve long-term survival rates—a 2013 analysis found that it improves life expectancy by a maximum of six months. At the same time, the operation reduces quality of life. For cancer patients with a BRCA mutation, however, the risk of contralateral cancer is much higher—about 47 percent over twenty-five years after the initial diagnosis. For these reasons, the National Comprehensive Cancer Network, for example, discourages contralateral mastectomy unless a patient is at high risk, as my mother was.

  My mother, of course, didn’t have the benefit of this research, so she made the best choice for her, according to the knowledge she had at the time.

  A lifelong feminist, she hadn’t changed her name after she married my father, but she did so now. As she wrote to me decades later, “I was so worried about you. I was worried that I wouldn’t make it,” and so she changed her name, “thinking that if I died you would not remember me and having the family name would help with that.” It was sad to lose her breasts. “My breasts were part of who I was as a person; it was part of my sexuality and it was part of my having experienced motherhood. It was a huge loss.” The blow to her sexuality, she says, might explain her strong memories of two events after the surgery. One of the wives at the law firm gave her a pretty nightgown, a slippery lime-green thing with short sleeves. “I thought it was nice to have something so feminine and pretty,” she says. She’d never had an engagement ring, and after the surgery, my dad presented her with a diamond ring, a romantic gesture that signaled to her that he cherished her for who she was. And his attitude was loving—he never made her feel self-conscious about her body, or as if she was less of a woman. “But it’s a sexual loss. There’s no doubt about it,” she tells me. She would look at herself in the mirror and feel like she looked like a kid again without her breasts. Her missing breasts presented a challenge she had to overcome. “When they’re gone, you have to readjust how you think about yourself,” she says. “On the other hand, because sexuality is a total body thing, having a piece of it missing isn’t going to erase the sexuality, it’s just going to alter it. It was sad, but at that point too, I was glad to be alive. What made me more sad at that time was the thought that I might not see you grow up.”

  The missing pieces of her weren’t the worst part of the whole thing, she says. Having cancer meant shuttling between terror and nor
mality. “There were nights during that period where I’d wake up in the middle of the night and just weep and think, ‘Oh, I’m not going to see Lizzie grow up and what’s going to happen to me and I’m going to miss Dick [her husband and my father] so much. You have those moments—there’s just no denying that—and during the day you just get up and have breakfast and read to your daughter and go to the park.”

  The cancer meant something major to the rest of the family too. My mother’s diagnosis was extraordinarily upsetting for her parents, for her mother in particular. No one quite remembers how the news spread to Lisa and Kathy—my grandmother or my aunt or my mother wrote letters or called the Illinois branch of the family—but my mother’s diagnosis terrified her relatives. Kathy hadn’t waited long after her mother’s death to seek out a then-controversial prophylactic mastectomy, a move my mother had initially thought was “a little extreme.” As for Lisa and Cris, of course they suspected the disease might be hereditary—Trudy, El, and Meg’s cancers certainly suggested that as a possibility—but after my mother fell ill, the Muehleisen curse felt undeniable, biblical, and impossible to avoid. As Lisa puts it, “When I found out about Gretchen I thought, oh, it’s going into the second generation. The prophecy is being fulfilled. This horrible thing is coming down into this next generation.”

  Though none of us would know cancer, we would know the curse of fear. And with a scalpel, we would choose to cut it out.

  3 | Gene Hunters

  The first or second time I came home from college, I spent many late nights in my mother’s home office, using her computer and the house’s only Internet connection to stay in contact with my new friends, chafing, undoubtedly, at the bonds of parental supervision that I’d been free of for the last few months. But if my parents could watch me—an adult—I reasoned, then surely I could watch them. Perhaps this explains why I went snooping. My fingers walked through the file drawer in the desk until they settled on the cancer folder. I just wanted a peek, I told myself. Just a peek.