A Patient talks about being treated in a landmark breast cancer clinical trial more than a dozen years ago

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Elementary School teacher Ellyn Perez made a dramatic return to Stanford recently. After Judy Shizuru, MD concluded her grand rounds talk on her study of those treated for stage –IV breast cancer with purified hematopoietic stem cells, she introduced Perez as the first patient treated over 10 years ago.
    Stage IV breast cancer, in which the cancer cells have metastasized beyond the site of the original tumor, is lethal in the vast majority of cases. Most patients have a less than 5% chance of surviving more than 10 years with standard therapy.
    In the 1980s and 1990s, many breast cancer patients were treated with high dose chemotherapy to kill the cancer. Because the chemotherapy also killed the blood and immune stem cells, those patients were “rescued” with an infusion of their own bone marrow cells, which were taken before chemotherapy. The problem was that, since cancer stem cells had spread throughout the body, most of these bone marrow samples also contained cancer stem cells.
This is where a Stanford discovery gave Perez a choice not available to other patients at the time. In 1988, Irv Weissman, MD and his team had made the first identification and isolation of a pure population of mouse blood-forming stem cells. Weissman and J. Michael McCune (now a professor at UCSF) formed a company called Systemix to find therapeutic applications for this discovery. By 1991, Weissman, Charles Baum and Ann Tsukamoto announced the first identification and isolation of human blood-forming stem cells. They showed that the purification method they developed, which used a modified fluorescence-activated cell sorter and antibodies that bind to stem cells, could be used to purged all contaminating breast cancer cells from samples of bone marrow or mobilized blood taken from cancer patients. Their method produced a pure population of blood-forming stem cells that could be used to regenerate patients’ blood and immune systems after high-dose chemotherapy was used to kill cancer.
    Perez became the first person treated clinical trial pulled together by Shizuru, Rob Negrin, MD and Weissman to test this method. She and other stage-IV breast cancer patients provided a sample of blood or bone marrow, they were given high-dose therapy to wipe out the cancer, and then were given back their own purified stem cells. A recent paper following up those original patients found that after more than ten years, patients given purified blood stem cells survived at more than three times the rate as those rescued with unpurified stem cells after chemotherapy.
    After speaking Grand Rounds, Perez gave more details about her story. She was initially diagnosed with breast cancer at age 34. She was treated with a lumpectomy, but the cancer returned two years later. A course of chemotherapy seemed to be successful, but then she began to feel a pain in her back.
    “I thought it was a disc, which would not have been surprising because my job involves a lot of bending and lifting,” Perez says. “My doctor agreed with me but thought he should run some more tests, considering my history.”
    Perez knew immediately when the doctor called her at home and asked if her husband was there and if she was sitting down. “He said that cancer had spread through my pelvis and all up and down my spine.” This is almost always a death sentence, even with modern therapy, Weissman says.
    Perez heard about the Stanford trial using purified stem cells and decided to enroll because the rationale “made sense.” In December 1996, after a course of high-dose chemotherapy, Perez was given back her own purified blood stem cells.
    Weissman, Shizuru, Tsukemoto and Negrin gathered in the tiny infusion room at Stanford Hospital, nervously watching resident trainee physician Keith Stockert-Goldstein take a small syringe with what looked like water (instead of the usual 1-2 liter bag of blood) to inject Perez with about 50 million stem cells (“about the number of cells in a hangnail,” says Weissman).
Just 12 days later, Perez’s blood-forming system had regenerated to a safe level. The age of regenerative medicine using purified stem cells had begun.
Of the 15 women with stage IV breast cancer enrolled at Stanford in the original trial, Perez became one of the five who still survive over a dozen years later. Four of the five have no evidence of the disease and are effectively cured. This cure rate (27%) compares very well with abysmal 10-year survival rates (less than 5%) for stage-IV breast cancer.
    Perez was shocked and saddened when she recently found out that more than 2 out of 3 of the other women in her trial did not survive, but she is glad she had the chance to be in the initial research group and is supportive of further trials. “I’m glad I have the chance to stand up and say, ‘It worked for me; don’t give up,’” Perez says.

Epilogue: Just a few years after Perez was treated, the large pharmaceutical company that purchased Systemix made a business decision to close down its work related to stem cell isolation and therapy. The Stanford Institute for Stem Cell Biology and Regenerative Medicine is now working to build a unit dedicated to purification of stem cells for clinical transplantation in order to restart these clinical trials at Stanford. Those interested in helping in this effort should contact Stephanie Witte at stephanie.witte@stanford.edu.