The Reasoner is a monthly digest highlighting exciting new research on reasoning, inference and method broadly construed. It is interdisciplinary, covering research in, e.g., philosophy, logic, AI, statistics, cognitive science, law, psychology, mathematics and the sciences. Each month, there is a column on Evidence-Based Medicine. Here is this month’s column: Testing Surgical Interventions for Breast Cancer.
“In God we trust. All others must have data.” – Bernard Fisher
A jailed breast surgeon this month had his sentence increased. He was previously convicted for performing unnecessary or inadequate surgeries, including the so-called cleavage-sparing mastectomy. The idea behind the cleavage-sparing mastectomy is to minimize any change in the appearance of a woman’s cleavage following surgery for breast cancer by leaving behind some breast tissue. The procedure is unorthodox and unregulated: It is not recommended by any health care guidelines because it is believed to increase the risk of breast cancer recurrence compared to standard mastectomy. Interestingly, the history behind those guidelines looks to provide an example of the importance of combining evidence from clinical trials with evidence of mechanisms.
The standard surgical treatment for breast cancer for much of the twentieth-century was the radical mastectomy popularized by Sir William Stewart Halsted. Halsted was widely acclaimed as a skilled surgeon. This is particularly impressive given that he was typically under the influence of narcotics. He had developed an addiction to cocaine after experimenting on himself in order to establish its local anaesthetic properties, and this addiction was cured only by getting addicted to morphine instead. However, it was his early adoption of anaesthetics in breast cancer patients which allowed him to develop the radical mastectomy by permitting more extensive and precise surgical procedures. Radical mastectomy was based on the anatomic theory of the mechanisms of breast cancer, namely, that cancer cells from the breast initially spread only as far as local lymph nodes where they are trapped for some time before being spread throughout the body. It was therefore thought that a local but large operation was necessary to remove the cancer before it had spread throughout the body: Radical mastectomy involved removing the breast, as well as nearby lymph nodes and chest muscles.
In the latter half of twentieth-century, the anatomic theory of the mechanisms of breast cancer was challenged by Bernard Fisher. As a newcomer to the field, Fisher had made a couple of observations about the state of breast cancer research. On the one hand, he was impressed by ‘how little information there was related to the biology of breast cancer and what a lack of interest there was in understanding the disease’. As a result, Fisher himself conducted a number of laboratory investigations into the mechanisms of breast cancer. On the basis of these investigations, he proposed an alternative systemic theory of the mechanisms of breast cancer, and he pointed out the implications of such a theory for the surgical treatment of breast cancer:
From those laboratory studies, we formulated an alternative hypothesis—that breast cancer was a systemic disease in that tumor cells were likely to have been disseminated throughout the body by the time of diagnosis and that more expansive locoregional therapy was unlikely to improve survival. As a consequence, less radical surgery was likely to result in similar outcomes to those obtained following radical mastectomy.
On the other hand, Fisher had also acknowledged the need for randomized clinical trials in testing proposed surgical interventions for breast cancer. Accordingly, he carried out a clinical trial in order to complement his laboratory investigations: ‘In that study, patients were randomly assigned to receive a Halsted radical mastectomy, a total (simple) mastectomy, or a total mastectomy followed by radiation therapy. In the 25-year follow-up of that study which was published in 2002 in the New England Journal of Medicine, the results from [the study] continued to indicate that there was no difference in overall survival, disease-free survival, or survival among the three groups of women}’. Arguably, it was only this combination of evidence of mechanisms together with evidence from clinical trials which led to guidelines shortly after recommending against radical mastectomy.
Words by Michael Wilde