imported_womens-health

The Management of Breast Cancer: Where We've Been, Where We're Going

By: Robert M. Gelfand, M.D.
At Issue
"High dose chemotherapy plus bone marrow transplant for breast cancer is an aggressive approach to therapy with serious morbidity -- but is it effective?" This question is the kernel of a controversy, one that will be answered only preliminarily at the May 1999 American Society of Clinical Oncology (ASCO) meeting. The discussion that follows will introduce several terms essential to the field of high-dose chemotherapy and transplantation, and will hopefully give the reader an understanding of the controversy surrounding this treatment.

Bone Marrow Transplant: The Basics

Stem cells are the key elements to bone marrow transplant technology. Also known as "pluripotential" cells, stem cells are very immature blood cells which have the capacity to develop into essentially all mature blood cell types ? those that we need to avoid anemia (red blood cells), fight infection (white blood cells), and maintain proper blood clotting after injury (platelets) -- as well as more stem cells. Stem cells usually reside in the bone marrow, but a small percentage of them circulate in the blood stream.


Organ transplants, in general, are performed to replace damaged organs with functioning ones. Transplantable organs include the cornea, heart, lung, liver, and kidney. Damaged or abnormal stem cells may also be replaced through transplantation. Bone marrow transplants (BMT) replace stem cells with those obtained or harvested directly from the bone marrow, while peripheral blood stem cell transplants (PBSCT) use those harvested from "peripheral" blood (i.e., by vein from the bloodstream). A patient who undergoes a BM or PBSC transplant has his or her stem cells replaced by another donor's stem cells (allogeneic transplant) or by his or her own stem cells (autologous transplant). In general, allogeneic transplants are performed to treat disease processes in which the patient's own stem cells are inherently abnormal, as with certain leukemias. Autologous transplants, on the other hand, are often used to replace stem cells that are destroyed by very high doses of chemotherapy or radiation. Just as a patient may store his or her own blood before a major operation, he or she may also store his or her own stem cells before receiving high doses of chemotherapy.

To date, only one of these trials has had positive results. In this trial, preliminary analysis supports use of HDC/BMT over standard therapy in certain patients with early breast cancer. In contrast, results from the four remaining trials, also preliminary, show no difference between the intensive HDC/BMT approach and standard therapy.
Although these trials address the same issues, they are dissimilar in other aspects. Numbers of patients enrolled, length of follow-up, and types and doses of chemotherapy differ among the studies, Most importantly, the trials are not yet complete, and the data and results have not yet been discussed by experts in the field. So, although it's exciting that these trials are progressing and that some Phase III data are finally available, no definitive answer has emerged. It should be emphasized that HDC/BMT should still be considered a valid treatment option by patients, physicians, insurance companies, and policymakers. Breast cancer patients should not be denied this option when appropriate simply based on preliminary results of these studies. This cautious view is reflected in statements offered by the National Cancer Institute, the American Society for Blood and Marrow Transplantation, and the Susan G. Komen Breast Cancer Foundation. Unfortunately, even after the May 1999 ASCO meeting, at which these trials will undoubtedly be discussed at great length, the preliminary nature of the data will likely keep the debate active.


As major improvements in the management of breast cancer continue to develop, it seems that milestones in therapy are reported at a rapid pace in both the medical literature and in the media. This exciting and stimulating research environment results from great scientific and public interest in conquering this disease. The fact that five randomized trials are actively acquiring data is another milestone; many oncologists in the past were skeptical that the trials would attract adequate numbers of patients. We are not, however at the point where we can answer the question of which approach is better. On the surface, it seems disappointing that four of the trials demonstrate equivalent outcomes between the two treatment arms. Nevertheless, it is too early to be discouraged. Hopefully, when these trials are finally discussed in the proper peer setting, a consensus of opinion will emerge regarding how to interpret these interim results and when more definitive results may be expected.

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