The Revlon money helped Slamon test the mouse anti-body on Diane Hinton and the nineteen other volunteers. It also helped him pursue a concept that had struck him just before Genentech decided to forge ahead with the Her-2/neu trials. He wanted to try the antibody in combination with cisplatin, a chemotherapy agent commonly used to treat ovarian and several other cancers. Several studies had shown it to be useless in treating breast cancer, but Slamon had come across other studies on the EGF-receptor antibody that suggested that cisplatin could greatly enhance that antibody's effectiveness. Supported by the Revlon endowment, he confirmed quickly that in the test tube, cisplatin has an enhancing effect on the Her-2/neu antibody as well. With those results in hand, he proposed trying a combination of cisplatin and the Her-2/neu anti-body as the best way to treat breast cancer.

Genentech's Her-2/neu team, under Mike Shepard, generated lab results that corroborated Slamon's theory about the cisplatin combination and recommended it to the Genentech management. Genentech embraced the idea wholeheartedly for its first crucial human tests. The company set up phase I and phase II trials at Sloan Kettering, UCSF, and UCLA to test the antibody alone in women with advanced breast cancer and at UCLA, under Slamon, to test it in combination with cisplatin.

In those tests, the first life was saved by Her-2/neu. Barbara Bradfield, a forty-eight-year-old with a recurrence of breast cancer in her lungs, was on her way to a wellness clinic in Mexico when she got a call from Dennis Slamon. In 1990, when she and hey husband, Dean, were on vacation in Big Sur , she had discovered a lump under her arm. Just two months earlier, she had had a clean mammogram, but she knew that a lump under her arm was a bad sign. As soon as she and her husband got back home, she called her doctor. "I had to fight like crazy to get an appointment without waiting for a month," she says. Bradfield, a matronly former school teacher whose mild demeanor suggests she would never confront the establishment, was furious. "Finally, when I got really nasty they worked me in the next day."

In addition to the lump, the doctor found a large mass in her breast. How it had escaped mammography is still a question that nags at her. "Either they missed it in diagnosis, or it grew that fast," she says, "I'm not sure what to think."

Bradfield, a devout Jehovah's Witness, lives in the upscale suburb of La Canada near Pasadena . Throughout her whole life she never thought about cancer, "There was no breast cancer in my family she reports. "I spent my life thinking I was somehow some blessed person. Nothing ever went wrong in my life, ever. Just everything I wanted, I got. I mean, that sounds ridiculous, but it's true. I can remember, you know, wanting so badly to be in the Pom-Pom girls in high school, the cheer squad. And when I got that, I thought that was everything, you know, that was so wonderful. And when I went to college and pledged a sorority, I got the sorority I wanted. I mean, it just was everything kind of went my way."

As doctors would later learn, many Her-2/neu-positive cancers explode out of nowhere into raging malignancies. Bradfield's friends urged her to pursue a malpractice suit, but she simply didn't have the energy. "You're too absorbed with the other fight," she explains. Doctors judged her cancer to be at stage 3 out of a possible 4, making it a highly life-threatening case, and told her that she had inflammatory breast cancer, which spreads with a terrible virulence. With her daughter Jennifer's help, she started reading up on cancer treatments. In one book, Jennifer found a description of inflammatory breast cancer. "She just got really, really upset because it sounded like there was just no hope," says Bradfield.

Her surgeon sent her to an oncologist in Pasadena . He prescribed a few tests, including one to determine whether the cancer had spread into her bone marrow. Bradfield had heard about the procedure, in which the marrow is extracted from the hip bone with a foot-long needle. "I was scared to death. They put me up on this table and never talked to me." The technician missed the first time he stuck the needle into her leg. When he finally got what he needed, he simply told Bradfield he was finished and instructed her to get dressed. "I got up off the table, and the nerves in my leg were still numb from the test, so I fell," she remembers. "At that moment, I knew what I was dealing with. It was like that experience made the whole thing sink in."

Indeed, Bradfield was terrified, but she was also furious. "I hated the man," she says with a vehemence that for her is not usual. "I mean, I cried all the way through. It's a good thing my husband was with me because he could sit and listen to what the guy was telling me in the room. I didn't hear a thing from that moment on. But then I started searching 'cause I knew I couldn't work with that person.

"I knew I had cancer, and I knew it was something that I had to deal with. I had a very positive attitude until that moment. I felt like a piece of meat up on that table. It was as if I had lost control of my life and my body, and it was a very bad experience." Like Anne McNamara, Barbara Bradfield, an earnest and intelligent woman, came to believe chat the medical establishment could not lie trusted to give her what she needed to beat her disease. She realized that she would have to become an activist and take charge of the decisions about her treatment.

"I tended to be very aggressive in my research," she says, "but a lot of women are like little sheep. They're led in to the doctor, they listen to what the doctor says, and that's what they do. And they don't look at anything else. And just from that first experience I had, I knew that I had to be in charge of things for myself. I couldn't rely on the doctor."

She found a new oncologist in Burbank . His first news was that she didn't have inflammatory breast cancer. "From that point on, I started getting all of my reports," she says. "I wanted everything in writing. I always knew what was going on." The doctor prescribed six months of chemotherapy to shrink the tumor, and then she underwent a mastectomy. She had more chemotherapy after the surgery, and then radiation.

Her treatment ended in the spring of 1991. "That's a scary time because while you're doing chemotherapy or radiation, you want to be done with it. But then when you're done with it, it's frightening not to lie doing something to fight the cancer."

It was also about this time that Bradfield began keeping a journal, or a diary of sorts. She can't explain exactly why she chose to do this, but given the grueling rigors of her cancer treatment, it's likely she thought it would be therapeutic.

"I guess I just needed to write out my feelings," she admits. "It helped me out. I go back sometimes and read through and see what I've gotten over, what I've accomplished. Sometimes I'll read it and think, gosh, I've been scared and depressed a lot, but it really is like that's when I write is when I'm scared and depressed. I don't write all the good times in necessarily, and so I started trying to do that so I could have some balance when I go back and read it."

Like most other cancer patients, Bradfield began to investigate alternative therapies. Given the terrible odds-half of all cancer patients die from the disease - it is not surprising that so many seek help outside the orthodox regimens. Few pneumonia patients look for alternative treatments because the standard protocol is almost always successful. Gathering information, Bradfield attended a convention of practitioners and students of alternative cancer therapies in Pasadena , near her home, and began to consider which of the regimens-they ranged from vitamins, herbs, and other nutritional supplements to relaxation therapies, psychotherapy, hormone therapy, and homeopathy-to pursue. The convention made a strong impression on her. "I met people who were survivors. I met one lady who had had lymphoma and lesions on her lungs, and she was there seven, eight years later."

Suddenly, in November of 1991, Barbara Bradfield and her family faced a tragedy that made her cancer seem trivial. Driving home from a fitting for her prosthesis, Bradfield heard a radio report of a fatal accident at the freeway exit near her house. She thought nothing of the story and, when she got home, went ahead with preparations for the weekly Bible-study class that was meeting that night at her house. But soon members of her group showed up and broke the news that twenty-three-year-old Jennifer had died in the accident. She had been seven months pregnant with the Bradfield's' first grandchild. The loss was indescribable. "We were real close. She was a real good support to me through all of the ups and downs of the first battle," says Bradfield. "She was in her seat belt," says Bradfield, recalling the terrible derails of the tragedy. "We think-somebody behind her said that it looked like she had leaned over and then she overcorrected. And she was very sick all the way through her pregnancy. Either she got sick or she dropped something and leaned over to pick it up. One of the two. So I will never know, I guess, until I see her again. I plan to. There's nothing worse than losing your child. Nothing worse."

Nine months later, in August of 1992, she was sitting in one of her Bible-study classes, absently fingering the area around her neck. She felt a spongy, marshmallow-like growth. "You wonder how you could have something like that in you and not know. The minute I touched it, I knew what it was. I didn't hear much more of the Bible Study that night" A needle biopsy confirmed that her breast cancer had recurred, and a CAT scan turned up a lesion on her lung. Bradfield had progressed to the "treatable bur not curable" Stage. The recurrence predicted in her original diagnosis had happened. Her doctor suggested she try high-dose chemotherapy, but she would have none of it "Done with that," she says firmly. "If I'm going to die, I don't want to die bald and throwing up.

"I'm a realist," she says. "I read everything. When the cancer comes back in the lungs and in the lymph glands, then there's not a lot out there to give you hope for that situation. I had seen people who had gone through this chemo, chemo, chemo. They died anyway, but they died so sick. I felt that the quality of life with my husband and kids was more important." Then the doctor, who happened to be a member of Slamon's loose network of Los Angeles-area oncologists, presented her with an option. "There's a guy doing a study at UCLA," he told her. "You want me to send your slides over?" Bradfield didn't pay much attention. "I said, 'I don't care. Go ahead. Sure.' And then I left."

She proceeded to investigate her options among alternative therapies. "I didn't feel like I was just opting to give up and die; I felt like I was choosing another method. Chemo hadn't worked for me the first rime, so there was no reason for me to think it would work the second rime around. I started researching all the clinics in Mexico . I figured my best bet was to detox and then to just work on making my body as strong as possible for as long as possible."

Returning to the Wellness Community in Pasadena for guidance, she decided to head down to Tijuana , Mexico , to check into a clinic chat administers the Gerson program. Devised in the 1940s by a German-born physician named Max Gerson, it is billed as an effort to rid the body of poisons and summon natural healing mechanisms. Patients eat a low-fat, vegetarian diet and each day drink a dozen glasses of freshly pressed fruit and vegetable juices. This regimen also requires that the patient have a coffee enema six rimes a day to speed up the flushing out of the body's toxins. Like many other alternative cancer treatments, the Gerson program offers little hard evidence of its benefits, and the medical establishment has little use for it, but at that point, Barbara Bradfield held the medical establishment in low regard. She sank two thousand dollars into a special juicer and made a reservation to spend three weeks-at five thousand dollars a week-at the clinic. Just before she and Dean were to take off, she got the call from Dennis Slamon.

"He told me that he was doing this study and that my oncologist had sent him my slides and that he had tested them and I was one of the highest expressers of this gene-Her-2/neu-that he had seen," she says. He asked her if she would consider being part of his study. She wanted to know if the treatment involved chemotherapy. When he told her yes (his part of the phase I trial combined the antibody with cisplatin, which can cause harsh side effects, like nerve pain and damage), she turned him down and explained that she was on her way to the Gerson clinic. He said he respected her decision and thanked her for her time.

The next morning, he called her back. "He said, I've been thinking about this all night, and you just can't do this.' He said, 'What you have is too aggressive and will grow too fast for it to be treated with that kind of a regimen. You need something stronger than food.'" Dean urged her to hear Slamon out. She went to UCLA, where Slamon spent two hours describing the treatment to her. What impressed Bradfield more than the details of the treatment was Slamon's unbridled enthusiasm. "Dennis is very busy and very distracted sometimes, but at this point he was finally getting to test his treatment on human beings, and he was just so excited. Everyone there had this air of anticipation, all the nurses and everyone else who was involved." She agreed to join Salmon's first trial group for the humanized Her-2/neu antibody combined with cisplatin. The regimen would last three months to test the safety and dosage range of the Her-2/neu antibody in combination with cisplatin,

In that first group were fifteen patients. Some had gotten to Slamon the way Bradfield had, through the recommendation of their oncologists. Others had read about Diane Hinton in the Los Angeles Times or had otherwise heard about the treatment and had fought to get into the trial. All fifteen women would have been considered terminal. In seven, the breast cancer had spread to the bone; in others, to the liver, the lungs, or the brain. Bradfield's cancer had metastasized not just to her lymph nodes but to her lungs. At the start of the trial, she had sixteen lesions.

Phase I trials seldom yield information about a drug's effectiveness, but within weeks Slamon began to see positive results. Bradfield says the tumor that was visible on her neck made her a group favorite because everyone could actually see dramatic progress. Within two weeks, her neck tumor had shrunk by half. "Everybody else was so excited because they felt like they could see what was going on in me; therefore, something good had to be going on with them, too."

The group evolved into an extraordinarily close support system. Slamon had set up the sessions so that all the women were together in one big room. Says Bradfield, "I think ail of us felt like this could be the magic bullet." "Everyone got attached," admits Slamon. "The nurses got attached to these women. The women got attached to the nurses. I mean, the one thing you don't do in oncology is get attached." The patients would come in with treats to share. "We would get real rowdy," says Bradfield. She got a particular kick out of a woman from Boston . "She was a very raucous kind of crass Jewish gal. She was hysterical. I just really liked her. She brought a cake from a porno cake place in Boston . It was this big cake with two big boobs in the middle. It said something funny about boobs and Dr. Slamon."

Several of the women were also exploring alternative therapies, and all shared whatever information they had. One woman of Chinese descent sought traditional remedies from China . "She'd bring back all these herbal things. She used to pass us out little packets with sea horses in them. They were awful. You're supposed to boil them. It was just disgusting," recalls Bradfield.

But the emotional attachment had its price. While the treatment showed some effect in some patents, it was hardly a cure-all for such desperately sick women. One young participant died almost immediately; her kidneys could handle the treatment. Several others died over the next weeks, including the Chinese woman. Each death was a terrible blow for the group. "It was too hard when people started dying," says Bradfield. "We became very emotional."

Slamon and the other medical professionals were accustomed to deaths in phase I trials, where any positive effect of the drug is the exception. "To a person, these women said in group meetings that they were making a contribution even if the treatment didn't help them personally," Slamon says. "So you do feel bad when you lose patients. On the other hand, you've gained the knowledge that allows you to treat the next group of patients more intelligently" Still, the doctors decided that in future trials patients would be treated individually.

The standard measure of a positive response in a cancer trial is a reduction of the rumor mass by at least 50 percent. Based on that criterion, Bradfield's response was extraordinary. The tumor on her neck disappeared entirely, and scans revealed that she had between four and six lesions in her lungs, down from sixteen when the trial started. Slamon says that between 20 and 30 percent of his group had positive responses. Some, like Bradfield's, were dramatic, though no one had a complete elimination of the cancer. At the end of the three-month trial period, Slamon, in consultation with Genentech, decided that the drug combination worked well enough to extend the trial for at least some of the participants.

Looking for significant scientific results, not slightly effective therapy, Slamon and Genentech made some tough decisions. They chose to drop the seven women with bone metastases from the trial. Even though each said that her pain had subsided with the initial treatment, there was no way to follow their progress with objective measurements, such as CAT scans, so their cases would provide little additional information. "There was some anger," says Bradfield. "You know there's something our there that could help you, but you're not allowed to have it. It's very frustrating."

After the deaths and the exclusions, only Bradfield and four other women were permitted to continue with the experimental treatment. Before they could proceed, the five women had to wait while Slamon's team and Genentech submitted required paperwork to the FDA. Bradfield was excited about her progress and eager to move on to the next stage. "It was very frustrating because there was like a period of six weeks or more while they were getting organized. We didn't get back to the study right away. That was real scary 'cause you felt like its going to grow again." At last, the five women began a second three-month cycle of antibody and cisplatin. One soon dropped out, however, because she could no longer tolerate the side effects of the cisplatin. Bradfield and the other three women completed the second course.

After the trial was over, Bradfield tried to stay in touch with the friends she had made. But over the coming months, husbands or other family members called her to say that her friends had died or were close to death. Beverly, the woman from Boston , was the last to succumb. " Bev's husband called me to say she was in and out of coma. And he put the phone up by her and had me talk co her," she says. "I had just gotten my tests at a year later saying I was clear. So he wanted me to tell her that- And Beverly, more than any of the rest of us, came into it saying, 'If this helps just one person, it's worth it.'"

Of the fifteen original volunteers for the Phase 1 study, only Bradfield survived. Repeated tests showed her to be totally cancer free. On each of many follow-up visits to Slamon, she asked what she should do next. Slamon had no precedent to follow. He remembers telling her, "We're where we haven't been before. We've used a new therapy and gotten a complete response with it. In someone who had sixteen to seventeen pulmonary nodules, do we continue the therapy? Do we stop the therapy? Do we stop the chemotherapy and continue the antibody? Do we stop everything together? There was no answer." One thing Slamon could not do was continue giving Bradfield cisplatin. The drug had already left her with nerve pain and hearing toss. More nerve damage would surely follow. So together they decided to try stopping it, Slamon remembers, "Knowing that the tumor may come back or it may not."

Bradfield often reflects on why she was the one who survived. Some of her answers are medical. "I think, looking back, that I was stronger than most of them coming into it. I'd been off of chemo for a year and a half, and I had been eating well and taking good care of myself." Other answers are spiritual. "As a Jehovah's Witness, I believe that we get answers to prayers, and we can get guidance. And I believe very strongly that that's what I did. that I was guided to that study."

Note: Barbara's story is from "Her2-The Making of Herceptin", by Robert Bazell

Random House 1998. As this book is now 4 years old, at our request, Barbara

Has updated her story.

I didn't think about adding a postscript - my life has become so normal ! (that's good isn't it ?)

October 2002 will mark ten years since beginning the Herceptin Study, April 2003 will be ten years Cancer free!! It's hard to believe how fast time has gone. At the age of 59 I have just started a new business!

BRUSHSTROKES BY BARBARA. I do murals, trompe l'oeil , Faux finishes. I love every minute. I never thought I'd have the energy again to do something like this, but I do!

Every day is such a sweet gift.