by Lizzie Stark
Would you cut out your healthy breasts and ovaries if you thought it might save your life? That’s not a theoretical question for journalist Lizzie Stark’s relatives, who grapple with the horrific legacy of cancer built into the family DNA. The BRCA mutation has robbed most of her female relatives of breasts, ovaries, peace of mind, or life itself. In Pandora’s DNA, Stark uses her family’s experience to frame a larger story about the so-called breast cancer genes, exploring the morass of legal quandaries, scientific developments, medical breakthroughs, and ethical concerns that surround the BRCA mutations. She explores topics from the troubling history of prophylactic surgery and the storied origins of the boob job to the landmark lawsuit against Myriad Genetics, which held patents on the BRCA genes every human carries in their body until the Supreme Court overturned them in 2013. Although a genetic test for cancer risk may sound like the height of scientific development, the treatments remain crude and barbaric. Through her own experience, Stark shows what it’s like to live in a brave new world where gazing into the crystal ball of genetics has many unintended consequences.
Copyright © 2014 by Lizzie Stark
All rights reserved
First edition
Published by Chicago Review Press, Incorporated
814 North Franklin Street
Chicago, Illinois 60610
ISBN 978-1-61374-860-2
Library of Congress Cataloging-in-Publication Data
Stark, Lizzie.
Pandora’s DNA : tracing the breast cancer genes through history, science, and one family tree / Lizzie Stark.
pages cm
Summary: “Would you cut out your healthy breasts and ovaries if you thought it might save your life? That’s not a theoretical question for journalist Lizzie Stark’s relatives, who grapple with the horrific legacy of cancer built into the family DNA. It is a BRCA mutation that has robbed most of her female relatives of breasts, ovaries, peace of mind, or life itself. In Pandora’s DNA, Stark uses her family’s experience to frame a larger story about the so-called breast cancer genes, exploring the morass of legal quandaries, scientific developments, medical breakthroughs, and ethical concerns that surround the BRCA mutations. She tells of the troubling history of prophylactic surgery and the storied origins of the boob job and relates the landmark lawsuit against Myriad Genetics, which held patents on the BRCA genes every human carries in their body until the Supreme Court overturned them in 2013. Although a genetic test for cancer risk may sound like the height of scientific development, the treatment remains crude and barbaric. Through her own experience, Stark shows what it’s like to live in a brave new world where gazing into a crystal ball of genetics has many unintended consequences”—Provided by publisher.
Includes bibliographical references and index.
ISBN 978-1-61374-860-2 (hardback)
1. Stark, Lizzie—Health. 2. Mastectomy—Patients—United States—Biography. 3. Breast—Cancer—Genetic aspects. 4. BRCA genes. I. Title.
RD667.5.S73 2014
616.99’449042—dc23
2014018310
Interior design: PerfecType, Nashville, TN
Printed in the United States of America
5 4 3 2 1
For the women in my family
and the men who love them.
Contents
Prologue
1 | The Ham Speaks for Itself
2 | “It’s Everywhere”
3 | Gene Hunters
4 | Myriad’s Monopoly
5 | Positive
6 | Watchful Waiting
7 | A Tale of Too Many Mastectomies
8 | The Black Cloud
9 | Barbie Girls
10 | Captain Kirk and Doctor Spock
11 | Ta-Ta to Tatas
12 | Heffalumpless
13 | Through the Looking Glass
Acknowledgments
Selected Bibliography
Notes
Index
“All happy families are alike;
each unhappy family is unhappy in its own way.”
—Leo Tolstoy
Prologue
My mother holds me on a sunny afternoon in Mesa Verde, Colorado, where we are vacationing with relatives. In the photo my father has snapped, I am an infant. My mother, dressed in a paisley muumuu and a turban, manages to smile at the camera, despite the fact that her clothing conceals a missing breast, the opening salvo in her strike against cancer diagnosed at age thirty. I do not yet know that she wears the turban because she has undertaken this two-week family vacation—a camping trip with an eighteen-month-old that seems insane to me in retrospect—between chemotherapy treatments that have taken her hair but not her fierce desire to live and see me through my childhood. I do not yet know that there has been so much cancer in her family that her sister and cousins will choose to remove healthy organs rather than risk a potentially fatal illness.
Twenty-four years later, I will carry this frightening experience—a mother sick first from breast cancer and later from thyroid cancer, the invincible god of my childhood weakened and injured by disease—to the genetic counselor with me. The waiting room walls are beige and smeared with stains from oily hair and anxious sweat. I find it terrifying that the genetic counseling department at this hospital shares an office with oncology, which is a place I desperately want to avoid. I am the youngest patient in the room by at least twenty years, except for the shadows I have dragged in here with me. The ghost of my great-aunt Trudy, dead of breast cancer at thirty-one, sits by a plastic plant and reminds me that wishful thinking is no panacea. My great-aunt Elfrieda’s shade sits further off in her wheelchair, the one that invasive ovarian cancer confined her to after the disease spread to her spine. The absence of my grandmother’s spirit is notable. My mother has not told her about this meeting; we don’t want to pile another cancer-related ordeal on a fading elderly woman who has already lost so much—breasts, ovaries, parents, sisters, and peace of mind—to the disease. She and her two sisters collectively endured six bouts of “women’s illness,” as cancer of the female organs used to be called. Of the four women in my mother’s generation, only one endured a breast cancer diagnosis, but all four chose double mastectomies. My story feels written before it’s even begun.
The genetic counselor has to fetch extra paper in order to record all the cancer in my family history. She explains the statistics to me in a gentle voice, as if trying to tell me my puppy has just died. I don’t understand why she sounds like that. “Fourteen percent chance of developing breast cancer at a minimum, if I have the gene, right?” I say. “As in one-four.”
“No,” she says, because I have misheard her. “As in four-zero to six-zero. Forty to sixty percent.” The numbers feel like a slap in the face, shocking and unacceptable. It is the first time I’ve confronted these statistics, and the first time that they make me feel nauseous with dread. Other doctors will give me other percentages, explaining that my lifetime risk of breast cancer could be as high as 87 percent.
Cancer runs on my mother’s side of our family because we happen to have a certain mutation on our BRCA1 gene. Every person has two pairs of BRCA genes in each cell of the body. BRCA1 is located on chromosome 17, and BRCA2 is located on chromosome 13. Scientists identified these genes in the 1990s and named them BRCA, officially for “breast cancer,” but unofficially for “Berkeley, California,” where the location of the first one was narrowed down. The person who named BRCA1, Mary-Claire King, had also hoped to name it for Victorian sc
ientist Paul Broca, who recorded an early cancer family, but she was only permitted four letters. Certain types of hereditary mutations in these genes can drastically elevate a woman’s chance of developing breast and ovarian cancer and certain other cancers, and can elevate a man’s chance of developing male breast cancer, prostate cancer, and other cancers. Though in my family my grandmother passed down this mutation, men can also inherit a mutation and pass it to their children. A person of either sex with a cancer-linked BRCA mutation has a 50 percent chance of passing that gene along to their kids.
We don’t know exactly how much a harmful BRCA mutation ups the risk of breast and ovarian cancer in women—estimates vary widely, according to Dr. Mary Daly, chair of the Department of Clinical Genetics at Fox Chase Cancer Center in Philadelphia, because they come from relatively small studies and because we are in the early days of medical genetics. The original estimates were higher, she says, because they came from early studies of the mutations: “To be in those studies you had to have at least four women [in the family] with breast or ovarian cancer,” which meant the studies looked at the grimmest, most intense mutations. Hereditary BRCA1 and 2 mutations take many different forms, and each mutation comes with differing levels of cancer risk; some mutations are completely harmless, while others raise risk modestly, or spike it dramatically. “No one has done the study that you really need, which is to do a random sampling of people in America,” Dr. Daly says. “So we have to rely on these smaller studies, where each of these studies has different limitations.” We have to do the best we can with imperfect science.
Now, seven years after my first visit to genetic counseling, and with the science still coming in, the estimates have been revised, mostly downward. But they are still large compared to ordinary women.
Lifetime chance of developing breast cancer Lifetime chance of developing ovarian cancer
Average woman 12% 1.4%
Woman with a BRCA1 mutation 55–65% 39%
Woman with a BRCA2 mutation 45% 11–17%
The size of these numbers is important because statistics like this propel BRCA carriers* to action, and they have only three options: surveillance to help catch cancer early, chemoprevention using estrogen blockers to head cancer off at the pass and temporarily reduce risk, or surgery to remove the offending organs to permanently lower risk.
In addition to having an elevated lifetime risk of developing cancer, BRCA carriers also tend to develop cancer at younger ages compared to the general population. The median age of breast cancer diagnosis is sixty-one. In my family—admittedly a tiny sample size—it’s more like thirty-four. Even cancer in one’s twenties is not unheard of among BRCA families. BRCA1 breast cancers are also more likely than other breast cancers to be triple negative. Triple-negative cancers are resistant to certain therapies and “generally have poorer prognosis than other breast cancers,” according to the National Cancer Institute. BRCA breast cancer is also more likely than typical breast cancer to recur in the unaffected breast.
BRCA mutations are pretty rare—about one in four hundred to one in six hundred people carry harmful versions. The rates among certain groups—most notably people with Ashkenazi Jewish heritage—are much higher. About one in forty people with Ashkenazi Jewish heritage carry a harmful mutation. By absolute standards, these numbers may not sound like a lot—in the general population less than a quarter of 1 percent of people have such a genetic alteration—yet this tiny segment accounts for fully 5 to 10 percent of all breast cancer cases and 15 percent of all ovarian cancer cases. It is a disproportionate burden.
It’s strange that something so small could cause so much havoc. Cancer is a complicated beast with many different causes, but at their core, they boil down to genetic anomaly. When several important segments of DNA in a single cell get screwed up—by heredity, by carcinogens, by viruses, or by natural mutations—cellular DNA doesn’t work correctly, leading to unchecked cell growth, aka cancer. The BRCA1 and BRCA2 genes produce proteins that help suppress the growth of tumors, and they play an important role in repairing cellular DNA. For this reason, when BRCA genes go awry, it’s harder for the body to stop tumors from growing, and cellular DNA isn’t repaired properly, which may mean it can quickly acquire other mutations that lead to cancer.
However, by itself an inherited mutation in one BRCA gene isn’t enough to cause cancer. Leaving aside the chromosomes that determine sex, we have two copies of each gene—one from our mother and one from our father—so if one doesn’t work, then the other can fill in. Inherited BRCA mutations raise a person’s chance of developing cancer because instead of starting out with two perfectly good genes, BRCA carriers start out with one broken copy. Since as we age we all acquire genetic mutations—the vast majority of which are benign—during cell replication or from environmental exposure, it takes fewer coincidences to muck up a BRCA carrier’s single working copy of those genes. Scientists have identified numerous inherited mutations within the BRCA1 and BRCA2 genes that disrupt their tumor-suppressing function and can lead to cancer. The alteration that runs in my family—3600del11—appears to be French.
Though the story of BRCA is partly one of scientific research and medical treatments, researchers racing to unearth the human genome’s hidden treasures, and military doctors in combat zones developing the crude tools that will later be used to rebuild BRCA-carrier Angelina Jolie’s de-breasted chest, it’s also the story of individual women and men choosing knowledge over ignorance and making extraordinarily difficult decisions.
To me, my family’s level of cancer feels biblical in scope, and this has mediated my personal experiences with the medical system. As I spoke with various relatives, I began to understand how much this has affected all of us—men and women, whether we carry a BRCA mutation or simply live close to someone who does. Through interviewing strangers who have dealt with the same issues, I also discovered that there is no one defining BRCA experience. Though there are commonalities, every particular family has its own flavor of sadness and triumph.
When I began my research, I did not know that it was possible to give a pregnant woman chemotherapy, but then I talk with a woman diagnosed with cancer while carrying her first child. She informs me that some chemicals cannot break the placental barrier. A man in his sixties describes watching his mother die from cancer when he was a child, and his voice still trembles. He details the guilt of passing a BRCA mutation along to his adult daughter. Shortly after she removes her breasts, he finds a lump in his own. Though it is not cancer, he learns what it means to wait for mammography results. I speak to a woman who watched her father, two aunts, and two cousins die of BRCA-related cancer. She is at the funeral for one of these cousins when the genetic counselor calls to tell her she is positive for the family’s BRCA mutation.
Another woman, diagnosed with breast cancer at forty-two, tells me about calling her sister to say she has a BRCA mutation, but when her sister picks up the woman is crying so hard she can barely get the words out. In the years following, all three of her siblings test positive for a mutation. The hardest thing for me to hear, though, is about her young son, who walked in on her once while she was changing clothes. Her mastectomy scars frightened him so much that he fled, crying.
Three sisters with a close relationship test together because their grandmother and several uncles on one side have died of BRCA-related cancer. One sister, a musician and a performer with a cabaret act, tests positive. Another sister tells me, “I remember when I called her to tell her that I was negative and I just burst into tears. And I just said to her, it should have been me, it should have been me. And she said, ‘No, I’m glad it is me.’ ” While the positive sister schedules her mastectomy and hysterectomy, the other sisters care for their mother, who is dying of cancer.
For many families, though, the stories aren’t so dramatic. Most of the women with young children that I talk to speak pragmatically, with matter-of-fact voices. They tell me they have chosen mastectomy because they want
to be there for their kids. I talk to women who feel the surgeries they had did not change their femininity, or even enhanced it, to women who are grateful for the knowledge, to people who do not want to open these issues and have decided not to test, or who tested but decided against surgery, and to women for whom this knowledge did not evoke a strong emotional response, or at least not one they are willing to share with me.
According to a 2014 study, less than half of the women who receive positive BRCA results elect to have a preventive mastectomy, while three-quarters decide on preventive ovarian removal, though only a fraction of those complete ovarian removal by the recommended age of forty. The rest do not choose to engage in any follow-up, or they try chemoprevention or live with their risk by engaging in surveillance. Typically, the women who choose surgery do so within months of their positive result.
All this, and more, is part of what it means to have a BRCA mutation.
Before their blood travels to technicians at Myriad Genetics—the lab that has somehow managed to patent a piece of the human genetic code—they might imagine the BRCA test as a delicate, sensitive tool, surely one of the apogees of modern scientific development. But positive results, once returned, sealed with their drops of blood, offer women a Faustian choice about whether to risk their lives or sacrifice their breasts and ovaries in the service of continued health. If the test represents the culmination of centuries of research, then the treatments—live with fear of cancer and practice constant vigilance or cut out internal organs—are crude and barbaric.
The ability to test human DNA for susceptibility to disease is miraculous, but it opens up a whole host of quandaries. Does it really benefit us to know what diseases lurk in our DNA? Is it OK to patent a human gene? Can we charge people with genetic cancer risk more for health insurance? Is it ethical or rational to remove healthy body parts? To engineer babies without these predispositions? The shining hope in the bottom of the box is, of course, the ability to out-sneak diseases like cancer, increasing our overall healthiness and life span. BRCA patients and researchers are not the first ones to face these decisions, and they won’t be the last, either. As genetic research continues, it’s likely that a growing number of people will confront similar quandaries. Already, we know of other genetic mutations linked to breast cancer, as well as mutations linked to bone cancer, leukemia, thyroid cancer, colorectal cancer, eye cancer, kidney and pancreatic cancer, to say nothing of the genes linked to conditions such as diabetes, certain types of arthritis, asthma, early-onset Alzheimer’s disease, and more. Perhaps one day we’ll simply carry our genetic code around on thumb drives that we’ll give to our doctors at checkin.
