Her-2: The Making of Herceptin, a Revolutionary Treatment for Breast Cancer - Brossura

Bazell, Robert

Brossura

ISBN 10: 0812991842 ISBN 13: 9780812991840

Casa editrice: Random House Publishing Group, 1998

Riassunto

Two years after she underwent a mastectomy and chemotherapy, Barbara Bradfield's aggressive breast cancer had recurred and spread to her lungs. The outlook was grim. Then she took part in Genentech's clinical trials for a new drug. Five years later she remains cancer-free.

        Her-2 is the biography of Herceptin, the drug that provoked dramatic responses in Barbara Bradfield and other women in the trials and that offers promise for hundreds of thousands of breast cancer patients. Unlike chemotherapy or radiation, Herceptin has no disabling side effects. It works by inactivating Her-2/neu--a protein that makes cancer cells grow especially quickly-- produced by a gene found in 25 to 30 percent of all breast tumors. Herceptin caused some patients' cancers to disappear completely; in others, it slowed the progression of the disease and gave the women months or years they wouldn't otherwise have had. Herceptin is the first treatment targeted at a gene defect that gives rise to cancer. It marks the beginning of a new era of treatment for all kinds of cancers.

        Robert Bazell presents a riveting account of how Herceptin was born. Her-2 is a story of dramatic discoveries and strong personalities, showing the combination of scientific investigation, money, politics, ego, corporate decisions, patient activism, and luck involved in moving this groundbreaking drug from the lab to a patient's bedside. Bazell's deft portraits introduce us to the remarkable people instrumental in Herceptin's history, including Dr. Dennis Slamon, the driven UCLA oncologist who played the primary role in developing the treatment; Lily Tartikoff, wife of television executive Brandon Tartikoff, who tapped into Hollywood money and glamour to help fund Slamon's research; and Marti Nelson, who inspired the activists who lobbied for a "compassionate use" program that would allow women outside the clinical trials to have access to the limited supplies of Herceptin prior to FDA approval of the drug. And throughout there are the stories of the heroic women with advanced breast cancer who volunteered for the trials, risking what time they had left on an unproven treatment. Meticulously researched, written with clarity and compassion, Her-2 is masterly reporting on cutting-edge science.
From the Hardcover edition.

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L'autore:

Robert Bazell is the chief science correspondent for NBC News. His reports, which appear on the NBC Nightly News, Today, and Dateline NBC, have won every major award in broadcasting. He has written for many publications, including The New Republic, The New York Times, and The New York Times Magazine. He lives in New York with his wife, Margot, and daughter, Stephanie.
From the Hardcover edition.

Estratto. © Riproduzione autorizzata. Diritti riservati.:

Discovering Cancer

One morning in the fall of 1978, Anne McNamara showered while her husband, Jeff, tended to Luke, their one-year-old son. As she soaped and scrubbed, she felt something unfamiliar in her left breast. "Uh-oh," she thought, a chill going down her spine. She had a history of fibrocystic disease. She tried to convince herself that all this could be was just another benign growth. Silently she recited the statistics: she was thirty-two; in premenopausal women, just one out of twelve tumors turns out to be cancerous. Fighting the impulse to panic, she sought comfort in the knowledge that there was no history of cancer in her family.

Anne McNamara brought uncommon understanding to her discovery. Having been a biology major and a chemistry minor in college, her first job had been in a laboratory of a scientist at Yale Medical School, who was carrying out medical research. She tested the effects of radiation and chemotherapy on cancer cells. Much as she wanted to believe that this lump, like many others she had previously had, would go away as she moved through her monthly hormonal cycle, she had a feeling that this one was different. In unguarded moments over the next couple of weeks, she probed the new growth. Had it changed? Did it feel different? Once you find a lump, she says, "You check it three times a day." After more than a month had passed without any change in the lump, she went to see her gynecologist, who said he thought it was just a cyst. Nonetheless, he sent her to a surgeon for a biopsy. Just to be sure.

A few days later, McNamara met with her doctor, James Finn, who offered her the choice that most women in her position then faced: he could do the biopsy and wait until McNamara came out of the anesthesia to give her the results, or they could agree ahead of time that he would remove her breast if the tumor turned out to be malignant. McNamara, typically matter-of-fact, chose the second option, the course of least emotional complication. As Jeff remembers it, "She did not fear the worst, but she prepared for the worst."

Anne's delicate appearance and honeyed Georgia accent belie her toughness. Her face settles naturally into a warm smile, and when she talks in her straightforward and low-key manner, her large green eyes and her high-arched eyebrows give the listener a clear window on her emotions. She's now a youthful fifty-two years old, with auburn hair flowing to her shoulders. Jeff, a muscular man with a neatly trimmed mustache and ice-blue eyes, had just returned from a four-year stint in the Air Force and was finishing up his business degree when they met. They lived in the same apartment building in New Haven; when Anne had totaled her motorcycle, and Jeff, an inveterate tinkerer, saw it crumpled in a corner of the garage, he asked her if he could take a crack at fixing it. They've been together ever since.

Anne's surgery was scheduled for the week after Thanksgiving. Jeff stayed home with the baby and awaited word from the hospital. In the operating room, the surgeon was stunned by the lump's size: five centimeters, the size of a lemon. Moments later, a pathologist confirmed that it was a tumor and it was indeed malignant. Dr. Jim (as the McNamaras called him) phoned Jeff from the operating room. "It's not good, Jeff." "How not good?" "Bad." Jeff paused to collect himself and then said, "Do what you've got to do. Take care of her the best way that you know how."

McNamara remembers slowly coming out of the anesthesia. "I was still extremely groggy, and I was trying to figure out if my breast was gone or not. I knew if it was, then it meant I had cancer. But I was so groggy that I clutched at my chest and I couldn't figure it out." As the anesthesia wore off, she realized that her torso was wrapped in a bandage. "I knew what that meant."

Her doctor was flabbergasted. "We were all flabbergasted," said McNamara. "Because it was cancer, and there I was, thirty-two years old, although now it's getting more and more common to happen in younger and younger women. But in 1978 it was still unusual enough that the doctor just couldn't believe it. Who knows where it came from? But it had probably been there seven or eight years by that time, they say, before you can feel anything."

In 1978, the initial treatment of breast cancer had not changed much since the end of the nineteenth century. Like Anne McNamara, most women undergoing surgical biopsy would drift off into the oblivion of anesthesia and grab at their chests when they awoke to learn whether they had lost a breast or not. When McNamara underwent surgery, enlightened doctors still considered the radical mastectomy, a decades-old procedure, the best choice for cases like hers.

McNamara's first question on learning that she had cancer was whether she needed chemotherapy. Even though she knew all about the side effects, like nausea and hair loss, she thought it might help keep the cancer at bay. But Dr. Jim tried to assure her that he had gotten all traces of the disease and recommended against it. McNamara felt relieved, but suspicious. "I remember thinking to myself, 'He doesn't really know that,' " she says. She spent enough time around cancer research to know that rogue cancer cells often escape to other parts of the body before surgery. Why not have chemotherapy as insurance against spread or recurrence? Dr. Jim argued that chemotherapy could actually spur cancer to recur and cited very preliminary Russian studies on premenopausal women that purported to show how chemotherapy could actually induce the spread of breast cancer. Those studies were soon discredited, but they illustrated a truth about medicine: state-of-the-art practices come and go as medical science proves and then discredits its latest thinking. Even the most immaculately reasoned advice can be faulty.

In fact, by the time Anne McNamara had her mastectomy, clinical trials were already under way that would prove the usefulness of chemotherapy immediately after breast-cancer surgery. McNamara did not care about trends in cancer treatment; she only wanted to take every precaution against her disease, and her instincts told her that chemotherapy would increase the chances of eradicating her cancer. While disheartened, she did not challenge Dr. Jim. As happens so often, the patient was protecting the caregiver. "He was trying to comfort me, and he was a friend." Thinking back on it now, McNamara wonders if chemotherapy might have saved her from the terror of recurring cancer. Then she dismisses the thought: "That was the accepted protocol at the time."

McNamara's instincts turned out to be better than her surgeon's. Ten years after her mastectomy, the National Cancer Institute issued an emergency clinical alert to physicians, recommending that chemotherapy follow soon after surgery for all but the least threatening breast-cancer cases. Clinical trials had demonstrated convincingly that chemotherapy administered right after cancer surgery--called adjuvant chemotherapy--could help prevent the disease from returning and could thus improve the patient's chances of survival. Nowadays, adjuvant therapy is the standard of care for most breast-cancer patients.

McNamara had good reason to be so cautious. Breast cancer in a thirty-two-year-old woman is extremely rare and especially frightening. For reasons no one clearly understands, when the disease occurs so early in life, it tends to grow aggressively. In the United States, the chance that a thirty-two-year-old woman will be diagnosed with breast cancer is less than one in four thousand. Only 6 percent of breast cancers in the United States strike women under the age of forty. The odds only grow worse as women age; the chance that an eighty-five-year-old woman will have developed breast cancer over the course of her lifetime is one in eight. In McNamara's case, the only relatively good news was that tests showed that the cancer had not yet spread to her lymph nodes, meaning that the chances of a recurrence were less than they would otherwise have been.

Though half of all women with breast cancer never suffer a recurrence after the initial treatment, they are still sentenced to a life of uncertainty, never sure if they will join the half that does have a recurrence; and when the cancer reappears, it is always deadlier than it was the first time around. For Anne and Jeff, breast cancer brought a particularly severe disappointment: Luke would have to be their only child. Female hormones can fuel the growth of breast-cancer cells, so a pregnancy, with its massive hormone surges, can greatly accelerate a recurrence, especially if diseased cells have managed to escape the surgeon's knife. Nowadays doctors will allow some breast-cancer survivors to risk a pregnancy, but when Anne was diagnosed it was out of the question. "That was a blow," says Anne. "We had waited for seven years after we got married to have Luke." With her hands folded calmly in her lap, she explains, "I knew it would be silly to have another infant if there was a chance I wouldn't be around to raise it. I didn't want to leave my husband with a new baby, and I didn't want to leave a new baby without a mother."

With her knowledge from the cancer lab, Anne could interpret the facts. Jeff had no similar understanding to temper his fear. He only knew that Anne might not always be there, and even twenty years later he is visibly upset at the thought, and he speaks freely about his confusion, fear, and frustration. His take-charge attitude had worked for him during his four years in the Air Force, and it had brought him success as a consultant to high-tech companies. But here was a problem that he couldn't solve. "If it had been a hole in the roof, I could have fixed it. But there wasn't anything I could do but be around to keep our life together. I just couldn't do much else."

"I mean, I was upset," he continues. "Not traumatized, but certainly upset. But Annie puts on a very good face, and is not an outwardly worrying type. And I think that has a lot to do with it." He pauses to laugh. "I mean, she's got a steel backbone."

McNamara left the hospital a week after her mastectomy, but she still faced reconstructive surgery. Her surgeon had recommended that she not have it immediately, so she waited nearly a year. "[He] said, 'Don't do it right at first because even months afterward, whatever reconstruction you have done, it's never going to look like a real breast. It's just not the same.' " She smiles wryly when she remembers the rest of their conversation: "He said, 'If you wait a while, then when you have it, you will be so glad to have a breast again that you won't be so picky that it doesn't really look like the other one.' " She pauses while the listener savors the full arrogance of that advice. McNamara is loath to launch an attack on her doctor for his clumsy statement. She simply dismisses his comment as "a male point of view."

Waiting for reconstruction was the hard part. "I didn't feel feminine. I didn't want to have to worry with the stupid prosthesis; I wanted to be able to go swimming and wear a bathing suit and not have to worry about the dumb thing."

In the meantime, she was determined to return to her life. A computer programmer since just after her marriage, she had taken a leave of absence to care for Luke full-time. She gave whatever time she had left over to her gardening and community work. She exercised as the surgeon prescribed and recovered full use of her left arm, which had been somewhat incapacitated by the surgery. "I put cancer out of my mind," she says.

McNamara is a modest woman who is reluctant to talk about herself. She maintains a quiet reserve and regards her misfortune as her own business, never telling people about treatment except for some very good friends. She says that many people, not those to whom she felt close, just don't know what to say. "It scares them. Yes, it terrifies people, especially breast cancer, and other women particularly. And because they don't know what to say, they don't treat you like a normal person. I don't want to talk about it with casual friends. I want them to invite me over and not have the topic of conversation be illness. Oh, how are you, isn't it awful? How do you feel? You look so pale." But others did not share her sense of discretion.

"Word got out," she says. Friends were stunned, particularly because she was so young. When she ran errands in downtown Branford, Connecticut, mere acquaintances would race across the street to say, "I just heard the most unbelievable thing. It can't be true!" The attention and sometimes tactless concern embarrassed her. "It affected me so," she says softly. "Once people know you have cancer, that's all they remember about you. They don't know what to say, and they avoid the situation. They don't mean to, but they write you off." She stops for a moment and then adds, "I just wanted to be treated like a normal person with a future."

There were some oddly funny moments, too. She describes how some friends would glance down at her chest as they were trying to figure out which breast was real and which had been reconstructed. "They just couldn't help themselves," she chuckles. After the initial burst of concern, people began to lay off the subject. And for a while, she was able to put cancer out of her mind.

Until this century, cancer was considered mostly a woman's disease, and it often carried the stigma of shame. Without modern diagnostic tools, physicians could more easily recognize cancers of the breast, cervix, and ovaries. Untreated breast tumors bulge and can break through the skin; untreated cervical and ovarian cancers lead to prodigious bleeding. Thus physicians believed erroneously that cancer strikes women more often than men. Until the last twenty years or so, cancer, and most especially cancer of the female organs, was not a topic of polite conversation. In the atmosphere of denial, women were all too often left to suffer with their illness alone, unable to find support as the disease destroyed them physically and emotionally.

When Anne McNamara's breast cancer struck, the shame associated with the disease was diminishing. Since the turn of the century, improved diagnostic techniques were proving cancer to be an equal-opportunity disease. But treatment for breast cancer has improved little over the last several decades, remaining a variation on the themes of surgery, radiation, chemotherapy, and hormone treatment. Separately and in combination, these options can be effective treatments and can sometimes bring about a remission that lasts long enough to be reasonably called a cure.

Surgery does not always excise the cancer entirely. Chemotherapy and radiation are often just random attacks on the problem, destroying much but not necessarily all of the cancer and usually harming healthy tissue in the process. Hormone treatment works for some breast cancer. The new approaches, such as adjuvant chemotherapy, can bring profound benefits, but they amount to little more than adjustments to the standard procedure. The problem is that breast cancer is unpredictable. Sometimes it is wholly contained in a tumor. But all too often it spreads from the tiniest tumor long before it can be detected or removed. Why do some cancers produce micrometastases, tiny bits of cancer that migrate from the original mass? No one knows.

The death rate for breast cancer stands as a dismal monument to ignorance. It has changed little in half a century. Every year the disease strikes more than 180,000 women in the United States and kills about 44,000. In 1950, the first year the government kept such records, 264 out of every 1 million white American women died of breast cancer. Twenty-five yea...

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• Editore: Random House Publishing Group
• Data di pubblicazione: 1998
• ISBN 10: 0812991842
• ISBN 13: 9780812991840
• Rilegatura: Copertina flessibile
• Numero di pagine: 240