Breast cancer researchers question tradition

July 02, 2003

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 appears 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, says Hillard M. Lazarus, MD, Director of the Blood and Marrow Transplantation Program at UHC and Professor of Medicine at CWRU. Dr. 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," Dr. Lazarus says. "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, Dr. Lazarus and his colleagues studied 511 primary breast cancer patients whose tumor 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 twenty-five 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% 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, Dr. Lazarus 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," says Dr. Lazarus. "But blood stem cell or bone marrow transplantation remains a promising therapy and requires further study."
-end-
University Hospitals Health System (UHHS) is the region's premier healthcare delivery system, serving patients at more than 150 locations throughout northern Ohio. The System's 947-bed, tertiary medical center, University Hospitals of Cleveland (UHC), is the primary affiliate of Case Western Reserve University (CWRU). Together, they form the largest center for biomedical research in the State of Ohio. The System provides the major clinical base for translational researchers at the Case Research Institute, a partnership between UHC and CWRU School of Medicine, as well as a broad and well-characterized patient population for clinical trials involving the most advanced treatments. Included in UHC are Rainbow Babies & Children's Hospital, among the nation's best children's hospitals; Ireland Cancer Center, northern Ohio's only National Cancer Institute-designated Comprehensive Cancer Center (the nation's highest designation); and MacDonald Women's Hospital, Ohio's only hospital for women.

Committed to advanced care and advanced caring, University Hospitals Health System offers the region's largest network of primary care physicians, outpatient centers and hospitals. The System also includes a network of specialty care physicians, skilled nursing, elder health, rehabilitation and home care services, managed care and insurance programs, and the most comprehensive behavioral health services in the region. For more information, go to http://www.uhhs.com.

The Case Western Reserve University School of Medicine is the largest medical research institution in Ohio and 16th largest among the nation's medical schools for research funding from the National Institutes of Health. Seven Nobel Laureates have been affiliated with the school.

The School of Medicine is also recognized throughout the international medical community for outstanding achievements in teaching. In 2002, it became the third school in history to receive a flawless accreditation from the Liaison Committee on Medical Education, the authority that grants accreditation to U.S. and Canadian M.D. programs. Annually, the School of Medicine trains more than 600 M.D. and M.D./Ph.D. students. Students learn from superb educators, researchers, and clinicians. CWRU's ground-breaking medical education program gives students clinical experience early in their training, teaches students through an innovative organ-based system, and fosters a professional and collegial atmosphere in which students are given considerable opportunity to pursue their special interests in biomedical science and clinical medicine.

CWRU has affiliations with University Hospitals of Cleveland, MetroHealth Medical Center, and the Louis Stokes Cleveland Veterans Affairs Medical Center. In 2002, CWRU and the Cleveland Clinic Foundation announced the development of the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University to prepare physician investigators. The college will admit its first class of students in 2004.

University Hospitals of Cleveland

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