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Terra Infirma

Can bone-marrow transplants save breast-cancer patients? There's little middle ground in the debateand lots of uncharted territory.

Linda McLaughlin sits on an examining table in the blood- and marrow-transplant unit of Rocky Mountain Cancer Centers. Though she's a heavyset woman, there's a fragility about her. Her voice, sweet and light like a child's, trembles between exultation and grief and sometimes explodes in a mini-burst of laughter. She has just returned from the dark shores of death, and she still carries with her all the terror and wonder of that experience. Next to her, sometimes putting a protective arm around her shoulders, sometimes helping fill in a detail or two of her story, sits her sister Rosemary Pagano.

Their family has a history of breast cancer; Pagano herself was treated for the disease five and a half years ago. "Our grandmother died when my mom was seven," Pagano says. "My mother, one of her sisters and then our older sister had it, also. Out of six females in our family, four have had breast cancer." She pauses momentarily. "You almost wonder what's worse," she asks, "having had it or wondering when you will?"

In October of last year, McLaughlin noticed a painful spot on her breast. "In my family, we automatically go to the doctor and say, 'What is this? Get it out of me,'" she says, laughing. She had a needle biopsy, and the results came on Halloween. "We were all dressed up at work," she remembers, "and I found out I had suspicious cells." The tears come as quickly and unexpectedly as the laughter.

The lump was large: seven centimeters. McLaughlin had chemotherapy to shrink it before surgery. Fearing there might be cancerous cells in her other breast, she opted for a double mastectomy. During surgery, seven cancerous lymph nodes were found under her arm. Then came four doses of chemotherapy and a choice: Did she want regular chemotherapy treatments or a program of high-dose chemotherapy, which used to be (and often still is) known as a bone-marrow transplant? This treatment is offered when breast cancer has metastasized to other parts of the body or, as in McLaughlin's case, is extremely likely to do so.

McLaughlin was 32 years old. Her doctor had told her that with conventional treatment, there was an 80 percent chance her cancer would recur within five years. At ten years, the chance of recurrence was 100 percent. She wasn't given numbers on the high-dose chemo but was told that it offered her the best chance of survival. Fifty-fifty, she thinks she heard somewhere. "I was in a fog," she says. "My thought process was, I want to be as aggressive as possible to get as much of the cancer as I can, to live as long as I can. And I figure any improvement over 100 percent is good."

Although in practice it's highly sophisticated, high-dose chemotherapy is based on a fairly primitive concept: Chemotherapy kills tumor cells; the cure fails when some of those cells escape or become resistant. So the solution would seem to be a high enough dose to wipe out each and every one of the little beasts. Unfortunately, chemotherapy is a clumsy instrument that poisons healthy cells along with cancerous ones and destroys bone marrow. A dose sufficient to wipe out all of a patient's tumor cells would likely kill the patient as well. But what, early researchers wondered, if some of that patient's bone marrow were taken out before chemo and then reinjected afterward and allowed to regenerate? Such transplants (using donated marrow rather than the patient's own) had been successfully used against leukemia and lymphoma for decades. Why not use them against solid tumors like breast cancer?

The experimentation began in the early 1980s. In 1990 Dr. Roy Jones and his wife, Dr. Elizabeth Shpall, major pioneers in bone-marrow transplant for breast cancer, came to Denver to head a unit at the University of Colorado Health Sciences Center. Presbyterian/St. Luke's, which is now affiliated with Rocky Mountain Cancer Centers, began offering the treatment in 1991.

Many breast-cancer patients are young; they often have children. They are desperate to live, and metastasis is almost always fatal. Sick women began begging for the treatment; activists pressed for broader access; reluctant insurance companies were shamed, pressured and sued into paying. More and more transplants were being done around the country. Some were given in a research setting such as that at University Hospital; others were simply offered by hospitals in search of revenue or responding to need.

In the early days, data collection was spotty, and it was difficult to get enough patients for the randomized trials that would provide definitive proof that the treatment worked. Many women, convinced that a transplant offered salvation, refused the possibility of being randomized to the non-transplant arm of a study. But transplant patients did seem to be living longer than expected, and the high mortality rate from the procedure itself was rapidly decreasing--from 15 percent to less than 5. New drugs came on line that aided bone-marrow regeneration. And researchers discovered that stem cells--immature bone-marrow cells--could be taken from the blood, obviating the need to drill into bone.

Up until this point, there had been little progress in breast-cancer treatment. Bone-marrow transplant seemed a shining beacon in the otherwise bleak landscape.

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