Special to Campus News by Eileen Korey,
director of news services, University Hospitals of Cleveland

High-dose chemotherapy coupled with a stem cell transplant do not improve the outcomes of post-operative patients with advanced breast cancer, according to findings of a multi-center study designed and conducted at the Ireland Cancer Center at University Hospitals of Cleveland (UHC) and Case Western Reserve University School of Medicine (CWRU).

The study appeared in the July 3rd issue of the New England Journal of Medicine. The findings should alter the treatment approach for patients with primary breast cancer that has spread to the regional lymph nodes, according to Hillard M. Lazarus, MD, director of the Blood and Marrow Transplantation Program at UHC and professor of medicine at CWRU. Lazarus' co-senior author on the Eastern Cooperative Oncology Group (ECOG) coordinated study was Martin S. Tallman, M.D. of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

"We found that an autologous stem cell transplant-high-dose chemotherapy followed by either bone marrow or blood from the patient herself-did not significantly increase the survival rate of women with early stage breast cancer that had spread to at least 10 lymph nodes in the axillary (arm pit) area," Lazarus said. "These results have enhanced our understanding of the disease and motivate us to explore alternatives to stem cell transplantation. It is evident that high dose chemotherapy destroys more cancer cells, but its complications can also be deadly to patients. We need to look at what we've learned about high dose chemotherapy and transplantation through this study, and use it as a platform on which to build similarly strong, yet safer treatments."

Nationwide, Lazarus and his colleagues studied 511 primary breast cancer patients whose tumors had spread to at least 10 lymph nodes under the arm. Half of the group was treated with conventional chemotherapy-only for six months-and the other half received the identical chemotherapy followed by high-dose chemotherapy and a stem cell transplant. All patients received the conventional dose of three drugs: cyclophosphamide, doxorubicin and fluorouracil. The high-dose chemotherapy consisted of cyclophosphamide and thiotepa.

Although there were many fewer relapses in the patients assigned to receive an autograft, the overall results showed that there was no significant difference in survival rates between the two groups. However, nine of the 511 patients died of transplantation complications. Nine others developed myelodysplastic syndrome (a pre-leukemia condition) or acute myeloid leukemia.

The procedure combines the administration of high doses of chemotherapy with the transplantation of stem cells from the patient's own blood or bone marrow. High-dose chemotherapy kills healthy blood cells as well as cancer cells, so stem cells are transplanted to restore the patient's blood production. The infused stem cells regenerate white blood cells to fight infection, red blood cells to carry oxygen and platelets that enable blood to clot.

These stem cells, taken from the patient's body (autologous) or from another person (allogeneic), are infused through a vein and travel to bone marrow to produce new white blood cells, red blood cells and platelets, enhancing the patient's health.

This life-saving treatment has been used successfully for more than 25 years to cure various types of leukemias and lymphomas. More recently, the treatment has proven effective for patients with multiple myeloma (bone cancer) and certain non-malignant disorders.

In the last decade, this modality was used with promising results in women with breast cancer whose prognosis is poor. Only 20 to 30 percent of such women with high-risk breast cancer are cancer-free five years after surgery.

In the 1980s and 1990s, some researchers found high-dose chemotherapy and autologous transplantation to be a promising therapy for breast cancer patients at high risk for relapse.

In a separate study in the same issue of the New England Journal of Medicine, researchers at the Netherlands Cancer Institute concluded that there is a benefit to high dose chemotherapy and transplant, with a 10 percent greater relapse-free survival among women who received the high-dose approach versus conventional therapy. This benefit was most evident among women under 40 years old with HER2/neu negative tumors (breast cancers that exhibit less aggressive features).

It should be noted that the chemotherapy regimens used in both studies, designed and activated more than a decade ago, differ from current conventional and high-dose chemotherapy approaches used in many cancer centers today. Moreover, Lazarus said he remains concerned about the secondary cancers and complications associated with high-dose treatments analyzed in this study.

"Conventional-dose chemotherapy remains the standard of care for most breast cancer patients who are at high risk for relapse due to lymph node involvement," he said. "But blood stem cell or bone marrow transplantation

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