High-Dose Chemotherapy With Stem-Cell Transplantation Offers Little Benefit for Women With Breast Cancer
It is estimated that over 200,000 U.S. women will be diagnosed with ]]>breast cancer]]> in 2003. Treatment typically involves some combination of local therapy and systemic therapy. In local therapy, ]]>radiation]]> or surgery is used to physically remove the cancer from where it originated in the breast. Systemic therapy—including ]]>chemotherapy]]> , hormonal therapy, and biological therapy—is used to shrink the breast cancer, prevent it from spreading or treat it if it has already spread, or prevent it from coming back after it is removed.
After a breast cancer has been removed, chemotherapy is often the method of choice for preventing recurrence. Chemotherapy is also used when the cancer has spread to the lymph nodes or more distant sites (metastasis). Conventional chemotherapy consists of a combination of drugs that kill cancer cells. But in the course of attacking cancer cells, chemotherapy also damages normal cells, causing side effects such as hair loss, loss of appetite, nausea or vomiting, diarrhea, and mouth sores.
During the 1990s, some physicians began treating their patients whose cancer had already spread with a combination of high-dose chemotherapy and stem-cell transplantation. Preliminary studies showed that higher doses of chemotherapy might reduce the risk of relapse and that stem-cell transplantation could be used to replace damaged cells lost from the intensive chemotherapy regimen. More recent studies suggest that high-dose therapy may not be as beneficial as once thought, but some physicians continue to prescribe it to their breast cancer patients.
Two studies in the July 3, 2003 issue of the New England Journal of Medicine compared high-dose chemotherapy plus ]]>stem-cell transplantation]]> with conventional therapy in women who had undergone surgery for breast cancer. Although one study showed an increase in the relapse-free survival of some women after high-dose therapy, neither study found a significant effect of high-dose therapy on overall survival.
About the Study
The first study included 885 women in the Netherlands who had undergone surgery for breast cancers that had already spread to their lymph nodes but not to distant sites. Half of the women were given five cycles of conventional chemotherapy and the other half were given four cycles of conventional chemotherapy followed by high-dose chemotherapy and stem-cell transplantation. The researchers followed the women for about five years then calculated their relapse-free survival and overall survival rates. Relapse-free survival meant the women were alive and without a breast cancer relapse at their last follow-up visit. Overall survival meant the women were alive at their last follow-up visit, regardless of whether they had had a relapse.
The second study was similar. It included 511 women in the United States who had undergone surgery for breast cancer and had evidence of spread to the lymph nodes. All of the women were given six cycles of conventional chemotherapy, but half were also given high-dose chemotherapy and stem-cell transplantation. The researchers followed the women for about six years then calculated their disease-free survival, overall survival, and time to recurrence. In this study, disease-free survival meant the women were alive and without breast cancer relapse or a new primary breast cancer.
The Dutch study showed that when compared to conventional therapy, high-dose therapy reduced relapse risk by 29% in women whose cancer had spread to 10 or more of their lymph nodes. Also, women under the age of 40, whose cancers showed signs of being less aggressive at the start of the study, were less likely to have a relapse. Five women died as a result of the high-dose therapy, while one woman died as a result of conventional chemotherapy. Also, nearly all women in the high-dose therapy group became postmenopausal, while most of the women in the conventional group remained premenopausal.
The U.S. study found no significant benefit of high-dose therapy on disease-free or overall survival. Within the high-dose therapy group, nine patients died within eight weeks of receiving the transplant, while there were no treatment-related deaths in the conventional group. Of note, nine women in the high-dose therapy group developed pre-leukemia or leukemia during the study, compared to no women in the conventional therapy group.
How Does This Affect You?
Because high-dose therapy with stem-cell transplantation was associated with an increased risk of treatment-related deaths, the development of pre-leukemia or leukemia, and the onset of menopause, and neither study found a significant difference in the overall survival, the risks of high-dose therapy probably outweigh the benefits.
Even so, these results may lead to promising treatments for breast cancer in the future. The Dutch study showed that certain groups of women—including younger women with less aggressive tumors—did better with high-dose therapy. Also, it is known that black women don’t respond as well to conventional therapy as white women, so it is possible that high-dose therapy would be particularly beneficial to black women. Finally, the researchers in the U.S. study suggested that high-dose therapy could be beneficial if the toxic effects of stem-cell transplantation can be avoided. They proposed that using peripheral-blood stem cells (which the Dutch researchers used)—versus bone marrow—in stem-cell transplantation could possibly decrease the risk of developing pre-leukemia or leukemia.
The next step is to design randomized studies that examine the benefits of high-dose therapy in certain groups of women or with alternative stem-cell transplantation methods. Until then, conventional chemotherapy remains the standard of care for women who have had breast cancer surgeries.
National Cancer Institute
American Cancer Society
National Cancer Institute website
Available at: http://www.nci.nih.gov/
Accessed on July 1, 2003
Rodenhuis S, Bontenbal M, Veex L, et al. High-dose chemotherapy with hematopoietic stem-cell rescue for high-risk breast cancer. New England Journal of Medicine . 2003;349:7-16.
Tallman MS, Gray R, Robert NJ, et al. Conventional adjuvant chemotherapy with or without high-dose chemotherapy and autologous stem-cell transplantation in high-risk breast cancer. New England Journal of Medicine . 2003;349:17-26.
Elfenbein GJ. Stem-cell transplantation for high-risk breast cancer. New England Journal of Medicine. 2003;349:80-81.
Last reviewed July 3, 2003 by ]]>Richard Glickman-Simon, MD]]>
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