Good, Bad News in Breast Cancer Studies
Long-awaited results from four major trials testing whether bone marrow transplants are useful in the treatment of breast cancer show that the transplants provide no significant overall increase in survival of those with an advanced form of the disease.
Although the results are preliminary, the finding is sure to lead health care providers to question the wisdom of spending as much as $100,000 per patient on the controversial procedure.
The results, released Thursday by the American Society for Clinical Oncology, are already provoking a lively debate.
If women who receive the transplants live no longer than those who do not, critics argue, why should the health care system bear the high costs and why should women be subjected to the toxic effects of the therapy?
Proponents argue that improvements in surgical procedures and the use of newer cancer drugs not included in the trials should produce better survival rates in the future. Specifically, they contend that the kind of infection-related deaths that resulted from the transplants during the trials can be avoided.
They also note that the transplants increased the length of cancer remission, improving the quality of the patients’ lives. “That, in itself, is a sign of hopefulness at a time in life when there is not a lot of hope,” said Susan Braun, president of the Susan G. Komen Breast Cancer Foundation.
Both sides agree that the studies have not gone on long enough to show small potential benefits, and argue that the trials should enroll more women who are currently seeking transplants outside the clinical trial system.
The studies do provide one surprising result: Survival of all women in the trials--including those treated with conventional cancer therapies--was about 20% higher than researchers had suspected, indicating that new chemotherapy regimens for breast cancer are better than those available only a few years ago.
An estimated 43,000 American women die of breast cancer each year. Among those whose disease is at an advanced state when it is detected, the five-year survival rate with conventional chemotherapy and radiation is only 22%, a stark figure that explains the great interest in new therapies.
Findings Will Fuel Debate
But the results announced Thursday were clearly disappointing. “Our hope was that the more aggressive approach would prove clearly superior,” said Dr. Richard Klausner, director of the National Cancer Institute. “These studies do suggest that [marrow transplant] is at least equivalent in terms of overall survival, but the added toxicity and costs . . . require it to to be superior if it is to become the standard of care.”
Nonetheless, “To say that it [bone marrow transplantation] doesn’t work is absolutely incorrect,” said Dr. Derek Raghovan of the USC School of Medicine. “The studies don’t say that at all. . . . It will take a lot more than this to convince me personally that the policy should be changed now.”
Ten states currently require insurers to cover bone marrow transplants for breast cancer, according to the American Cancer Society. Some Medicaid programs also cover them, as does the Federal Employees Health Benefits Program. Medicare does not, however, considering them an experimental procedure. The mandated coverage may be difficult to overturn.
Insurance companies are unlikely to make any immediate changes in their reimbursement procedures, at least until more detailed results are presented next month at the annual meeting of the American Society of Clinical Oncology, said Karen Ignani, chief executive of the American Assn. of Health Plans. Even then, they may not make changes in the face of public desire for the procedure. “The issue has become very politicized,” she said.
Bone marrow transplants were begun in the 1970s for the treatment of leukemia and lymphoma, and were fairly successful for those diseases. They were first used for breast cancer in the late 1980s, and preliminary reports suggested they could be a valuable tool there as well.
The transplants are not themselves an anticancer therapy. Rather, they support the patient’s body, allowing doctors to treat tumors much more aggressively.
In such cases, physicians use as much as 20 times the normal dose of cancer drugs, hoping that the intensive therapy will wipe out all cancer cells that may have migrated from the original tumor site to other parts of the body. Such treatment also kills bone marrow cells, however, and would be lethal if those cells were not replaced.
Marrow can be taken from either the patient herself or from another donor. In “autologous” transplants, physicians remove some of the patient’s own bone marrow cells before the therapy, then reinfuse them into the bloodstream after the cancer drugs have been naturally cleared by the body. In “allogeneic” transplants, the replacement cells come from a closely matched donor.
But the patient runs the risk of infections and other complications while her immune system is impaired by the lack of marrow. In the early days of bone marrow transplants, the death rate from such complications could be as high as 20%. At least one of the new studies had a death rate of that magnitude, but the others were somewhat lower, closer to 5%.
With newer techniques, the death rate can be much lower, according to Dr. James Doroshow of the City of Hope Medical Center in Duarte. At the center, which performs about 170 bone marrow transplants for breast cancer each year, the death rate associated with the procedure is about 1%. “That could have a big impact on the interpretation of the results,” he said.
As with any new medical treatment, physicians had to compare bone marrow transplants to conventional therapy to determine whether it offers a significant benefit.
Of the 12,000 American women who have received a bone marrow transplant, only about 1,000 participated in a trial. This is because many women are placing such hope in the procedure that they seek out physicians who would perform a transplant rather than enroll in a trial where they stood only a 50% chance of receiving it.
Despite the discouraging results of the new trials, physicians say it would be premature to stop doing the procedure in appropriate cases. “Everyone would hope, however, that the equation would shift and that more transplants will be done inside trials,” said Dr. Allen Lichter of the University of Michigan School of Medicine, president of the American Society of Clinical Oncology.
Some experts suggest that trial results would improve if Adriamycin and taxol, the two most effective drugs against breast cancer, were used in combination with marrow transplants. None of the trials reported Thursday used those drugs, Doroshow noted. City of Hope is among those testing the combination and preliminary results look encouraging, he said.
The National Cancer Institute is also sponsoring trials where the transplants are used at an earlier stage of cancer progression.
A summary of the results is available at the Web site of the American Society for Clinical Oncology at www.asco.org.
