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BMT in breast cancer

BMT in breast cancer - Education and debate Presumed...

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Education and debate Presumed benefit: lessons from the American experience with marrow transplantation for breast cancer H Gilbert Welch, Juliana Mogielnicki 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. Early reports 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 chemo- therapy 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 correlated with survival.” 2 But other oncologists were more sceptical. In the same article one pointed out that the notion of dose-response was purely theoretical and also applied to toxicity: “It’s a hypothesis . . . and higher dosages are more toxic.” 2 And there were few data. The first report in the gen- eral medical literature on the treatment’s efficacy for breast cancer appeared in the Annals of Internal Medicine in 1988. 3 The article reported on 172 women from 27 studies. The summary response rate (defined as tumour shrinkage > 50%) was 58%. There were no controls. A few months later the Annals published a review that included 159 women and noted an 80% response rate. 4 In both articles the authors were cautious, concluding: “Critical evaluation will require controlled trials,” and “response rates that are probably superior to the best available with conventional therapies . . . although not yet associated with improved survival.” Comments made to the press, however, were less cautious. In the news section of the Journal of the National Cancer Institute , one author said: “I think this shows that ABMT can be a very effective form of treat- ment.” 5 A similar sentiment appeared in the Los Angeles Times : “A combination of bone marrow transplants and very high doses of anti-cancer drugs may be able to double the survival rate of patients with advanced breast cancer, a Boston researcher reported last week.” 6 Patients in the media Other factors converged to make bone marrow transplantation for breast cancer a big story. Women’s issues were prominent. Breast cancer was both common and feared. Transplantation was a source of
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