Convinced by doctors that bone marrow transplantation offered the best chance at survival, thousands of women with breast cancer have agreed to the controversial procedure — despite the lack of proof that it could save, or even prolong, their lives more than standard therapy.
Indeed, so many women — about 5,000 women a year — now undergo the treatment, arguably the most devastating procedure in modern medicine, that breast cancer has become the most common reason for transplants, edging out leukemia and lymphoma, for which there is considerably more evidence of efficacy.
Now, it appears that this faith in transplants for breast cancer — and advocates’ demand that insurers pay for it — may have been misplaced, or at least premature.
Pressured by patients and doctors, researchers have agreed to take the unusual step of posting abstracts of two US and three foreign studies on transplants and breast cancer on the Internet next month. They will give more details in May at the American Society of Clinical Oncology meeting in Atlanta.
That decision stems from a meeting of researchers and patient advocates in February at the National Cancer Institute, which sponsored the two American studies.
Susan Braun, a patient advocate and president of the Susan G. Komen Breast Cancer Foundation in Dallas who was at that meeting, says the group was concerned about not releasing findings before the data were fully analyzed, but didn’t want to “hold on [to the findings] waiting for the meeting in May.
Until they’ve fully analyzed their data, the lead researchers aren’t talking, even to collaborators, including some in Massachusetts, where insurance companies have been forced to pay for the transplant treatment.
That silence is fueling speculation that at least one study found no benefit for transplant in women with Stage IV (metastatic) cancer and another is inconclusive for women with Stage II or III cancer and 10 or more lymph nodes containing cancer.
Concern is also growing that insurers may stop paying for the $50,000 to $100,000 procedure, though Karen Ignagni, president of the American Association of Health Plans, a managed care group, denies it. “It would be wrong to suggest a conclusion that would make patients concerned about access to these procedures until we know what the research says,” she says.
But patients are nevertheless bracing for bad news. Amid the confusion, two things seem clear. One is that, in general, when studies show an obvious benefit of one treatment over another, they are stopped early, as happened when the drug tamoxifen was found to reduce the risk of breast cancer in high risk women.
These studies are “clearly not a homerun . . . or they would have met the stopping criteria,” says Dr. Steven Come, director of hematology/oncology at Beth Israel Deaconess Medical Center and a contributor to one of the American studies.
The other is that the studies have not gone on long enough to be truly informative. The American study called CALGB followed 874 patients for an average of 37 months; one called ECOG followed 553 patients for an average of 31 months. Usually, longterm survival is given after five years, not three or less.
Furthermore, even if the studies show no clear benefit for transplantation — in which patients are given near-lethal doses of chemotherapy, then “rescued” by infusion of stored immune cells — subgroups of women might still benefit, says Dr. John Durant, executive vice president of the oncology society.
“It’s a horrible situation for women,” says Fran Visco, president of the National Breast Cancer Coalition, an advocacy group. “If the studies are ambiguous, women should not have a transplant, except in a clinical trial. If more women had been told by their doctors to do that, we’d have better answers by now. Insurers should also be compelled to fund the trials like these that can provide better answers.”
But “in the absence of data, it’s mutual self-deception,” for women and their doctors to assume a transplant is better than standard therapy, says medical ethicist George Annas, professor of health law at the Boston University School of Medicine. Transplants are “heroic.” To put women through them without more evidence is mere “faith healing.”
Indeed, Memorial Sloan-Kettering Cancer Center in New York does not offer the procedure for breast cancer patients and in the past, only offered it in research settings.
If the findings do turn out to be ambiguous, says Braun of Dallas, it “will leave women very much where we are now. We would like to have seen more people in the clinical trials.”
“No kidding,” says Dr. Mary Horowitz, scientific director of the International Bone Marrow Transplant Registry and the Autologous Blood and Marrow Transplant Registry in Milwaukee.
Recruiting was a nightmare, she says, “because everyone thought they knew the answers,” and because mortality from the transplant procedure itself has dropped from about 15 percent to 3 to 5 percent for women with Stage II or III breast cancer. “I can see why women decided to take the chance.”
But what is “particularly wrenching is there was such a lot of hype around this procedure for women with breast cancer when it first came out,” in the early 1990s, says Grace Powers Monaco, a lawyer and head of the Bethesda, Md.-based Medical Care Ombudsman Program, which evaluates recommendations for transplants for HMOs and patients.
Some of those early studies found that as many as 20 to 30 percent of women with advanced breast cancer survived at least a few years after transplant, says Come of Beth Israel.
But that, as Monaco sees it, prompted women to feel, “ `I should get this treatment and I will not be randomized.’ Because of that, the data was delayed many years because people did not fill up the clinical trials.”
Indeed, faced with mounting pressure, including lawsuits, many insurers agreed to pay for the procedure, and some states, including Massachusetts, now even mandate coverage by law.
The bottom line, sadly, is that there will be no bottom line in the near future, although four other randomized studies on transplants for breast cancer are underway through the National Cancer Institute.
For the moment, though, the expected results from the current studies are simply “not sufficiently mature to analyze,” says Dr. Thomas Spitzer, director of the bone marrow transplant program at Massachusetts General Hospital and a contributor to the American study called ECOG, run by the Eastern Cooperative Oncology Group.
Come of Beth Israel, who participated in the CALGB trial, agrees. “While awaiting further analysis and follow up from these trials, women contemplating a transplant owe it to themselves to seek a variety of perspectives before making a final decision.”
“Personally, I can’t make up my mind” about the data, muses ASCO vice president Durant, who lost his wife to breast cancer. But he’s guardedly optimistic. Because these studies were so short-term, there’s “lots of time for benefits to appear.”
SIDEBAR:
How to learn more
To read more about the emerging data from studies of bone marrow transplantation for breast cancer, you can visit the website of Cancer Letter, www.cancerletter.com. The letter is privately published by journalists Paul and Kirsten Boyd Goldberg.
For the National Cancer Institute’s position on the issue, visit http://cancertrials.nci.nih.gov. Beginning April 15, you can read preliminary results of the studies and suggested interpretations of them at www.asco.org, the site of the American Society of Clinical Oncology.