False Hope: Bone Marrow Transplantation for Breast Cancer (review)

Critics now routinely cite stem cell transplantation for advanced breast cancer as the quintessential example of the misuse of an insufficiently evaluated medical technology. During the 1990s, between twenty- and forty-thousand women underwent this procedure, which was later shown by randomized controlled trials to be of little value. Rettig and colleagues have written a remarkably well-researched history of this episode.

The story begins in the early 1980s, when oncologists first proposed using high-dose chemotherapy followed by autologous bone marrow transplantation for women with incurable breast cancer. The idea was that the chemotherapy would kill as many remaining cancer cells as possible, including those that were invisible. Although this process would also damage the body’s normal cell lines, the bone marrow infusion would restore them. The hope was that women undergoing this procedure would be cured or at least have their lives prolonged beyond what standard chemotherapy could accomplish.

The authors are very good at demonstrating the multiple social influences on the scientific evaluation of the combination of chemotherapy and transplantation. We learn that the earliest proponents were at Boston’s Dana-Farber Cancer Institute. There, Emil Frei III, a renowned hematologist-oncologist, led a team of specialists, including William Peters and Karen Antman. Peters and Antman would complete a series of Phase 1 and 2 studies that they believed demonstrated better treatment responses, improved survival, and, possibly, curability. Thus encouraged, Peters also began to test the procedure in women with advanced, but not necessarily metastatic, breast cancer.

By the early 1990s, oncologists found themselves at a complicated crossroads. Should they assume that high-dose chemotherapy and transplantation (stem cells gradually replaced bone marrow as the preferred agent) was the treatment of choice for advanced breast cancer, or should they enter patients into only new randomized controlled trials designed to compare transplantation with standard chemotherapy?

It should be noted that both Peters and Antman favored clinical trials to try to obtain definitive proof of the relative value of the two strategies. But they had opened the barn door, and the horse was gone. As Rettig and colleagues show, numerous factors combined to favor the use of transplantation outside of clinical trials. These included: (1) entrepreneurial oncology, in which cancer centers viewed technologically sophisticated procedures like transplantation as moneymakers; (2) patient demand, in which women with breast cancer, building on a rich history of activism, assumed that a more aggressive treatment would necessarily be advantageous; and (3) the media, which, the authors believe, did not sufficiently caution against a risky and toxic therapy.

Nor did the usual brakes in the system function properly. For example, insurance companies, which normally would have declined to cover such an expensive experimental procedure, bowed to pressure and funded it. The courts, when hearing cases in which insurance companies had understandably denied coverage, often sided with the plaintiffs. And when health insurers demurred, state legislatures passed mandates requiring that they cover transplantation for breast cancer. It is not surprising that it was extremely difficult in this climate to get women to voluntarily enter clinical trials in which half of them would not receive a transplant.

But eventually several trials were completed, and the results, presented at the 1999 meeting of the American Society for Clinical Oncology, were a bombshell. Bone marrow or stem cell transplantation provided no better survival for advanced breast cancer and, due to its toxicity, at times killed women early in their treatment. One study that showed a survival advantage for transplantation was eventually shown to be fraudulent, a harrowing story that the authors tell quite well.

Having thoroughly documented such a lapse in the evaluation of technology, Rettig and colleagues conclude with a sound recommendation for preventing similar events in the future: the establishment of a “public–private partnership” of health professionals, insurers, research funders, and patients who will evaluate and regulate cutting-edge research initiatives...