Presumed benefit: lessons from the American experience with marrow transplantation for breast cancer

Few stories in medicine are as sobering as the American experience with autologous bone marrow transplantation (ABMT) for treating breast cancer. It is a story of young women dying from aggressive disease, well meaning physicians trying to be equally aggressive in treating it, and lawyers arguing that insurers should pay the bill. It is also a story of professional interests, weak research, financial gain, politics, and fraud. Because of its potential relevance to complex cancer therapies currently in development (such as gene therapy) we recount here the story and its lessons. #### Summary points For over 10 years bone marrow transplantation for breast cancer was seen as an example of the general dilemma about who should pay for costly new life saving therapies This characterisation obscured the more basic question: Did it work? Intermediate outcomes and inadequate controls made preliminary evidence misleading Statements by physicians in the literature and the general press reinforced the presumption of benefit, as did the decision of government bodies to mandate insurance coverage The findings of major randomised trials did not support the use of the therapy This experience provides lessons relevant to complex cancer therapies currently in development Bone marrow transplantation was first performed to treat primary bone marrow disorders, but in the late 1970s it started to be used also for “rescuing” patients (using their own marrow) after supralethal chemotherapy or radiation for solid tumours.1 By the mid-1980s there were strong proponents for using it this way in advanced breast cancer—on the basis that higher chemotherapy doses would be expected to kill more tumour cells. The enthusiasm for this hypothesis was evident in comments made to the New York Times in 1989 by the head of the breast cancer section at the National Cancer Institute: “The evidence is absolutely convincing that the dose intensity is …