How Clinical Trials Saved Women With Breast Cancer From Disfiguring Surgery

Bernard Fisher’s battle against the radical mastectomy

Surgical instruments
(John Schults/Reuters)

Before 1971, if you had breast cancer, chances are you’d have to get your breast cut off. Surgeons had been taught one thing: radical surgery saves lives. It was Bernard Fisher who changed their minds,  getting reluctant breast surgeons to enter their cancer patients into clinical trials that tested less aggressive surgery against the Halsted radical mastectomy.   Thanks to these clinical trials, probably hundreds of thousands of women with breast cancer have avoided disfiguring surgery.

Although his career was not without controversy, Fisher’s contributions should not be forgotten.  He turns 95 this month.

The treatment of breast cancer with radical surgery extended back to the work of William S. Halsted, the revered late 19th-century Johns Hopkins University surgeon who, popularized the radical mastectomy, which involved removing not only the cancerous breast but also the underarm lymph nodes and the chest wall muscles on the side of the cancer.

Halsted’s operation was based on the best science of the day—the notion that breast cancer spread slowly and only entered the bloodstream late in its course. Hence, doing a large, local operation was the best way to try to remove all of the cancer in the body. The problem was that the radical mastectomy did terrible damage, leaving women with huge holes on their chest walls.  Without their lymph nodes, they developed massively swollen arms, a condition known as lymphedema.

Fisher, who went to medical school and trained at the University of Pittsburgh, and then later did research at the University of Pennsylvania and in London, had made observations that called Halsted’s theories into question . He noted that cancer cells entered the blood early in their course, probably before doctors discovered them. If true, doing such a large operation at the site of the cancer made no sense. What would determine whether or not a woman lived was the ability to kill these wayward cells, which is now accomplished by chemotherapy.

Fisher had also become enamored of the randomized clinical trial, a relatively new development in medicine in which innovative procedures were formally compared to older ones.  Patients would agree to enter a trial without knowing which treatment they would receive. To Fisher, such trials were a “highly sophisticated methodology” that represented a “major step toward transforming medicine from an art to a science,” as he wrote in his paper The Biological and Clinical Justification for Relegating Radical Breast Operations to the Archives of Surgical History.

Most of Fisher’s fellow breast surgeons wanted no part of this, retaining faith in the radical operation they had learned from their mentors. Some of them even accused Fisher and another renegade surgeon interested in less aggressive operations, George Crile, Jr. of the Cleveland Clinic, of potentially “murdering” the women who would get smaller operations, such as removing only the breast or a portion of the breast—now called a lumpectomy.

Yet Fisher and his National Surgical Adjuvant Breast and Bowel Project (NSABP) finally prevailed, beginning to enroll patients in 1971. By the late 1970s it appeared that, as he had suspected, women with early-stage breast cancers did just as well with these more limited operations, often accompanied by radiation and chemotherapy, as women who had radical mastectomies. In 1985, the New England Journal of Medicine published two of Fisher’s studies that definitively proved these earlier findings.

Fisher became a medical hero, and rightfully so. In 1985, he was awarded the prestigious Lasker Award for medical research.  Many colleagues thought he deserved the Nobel Prize. But the same self-assured and pugnacious attitude that had helped him triumph over surgical conservatism soon landed him in hot water.  In 1994, the media reported that one of the surgeons who had participated in Fisher’s research had falsified data on 99 cases. Yet neither Fisher nor the National Cancer Institute (NCI), which was in charge of the research, had chosen to go public with this information.

Women, especially those who had undergone less aggressive surgery based on Fisher’s research, were furious, calling the fraud and subsequent secrecy a “shocking breach of trust,” as Sharon Batt put it in her book, Patient No More: The Politics of Breast Cancer.  The NCI and the University of Pittsburgh, where Fisher was a professor, removed him as head of the NSABP due to concerns of scientific misconduct.

How could Fisher have made such a colossal mistake?  It turns out that he and his colleagues were already in the process of re-examining the data without the errant 99 cases.  Eventually they concluded that nothing had changed: a lumpectomy was just as good as a mastectomy which was just as good as a radical mastectomy. The scientific method, which took into account the possibility of fraudulent data, had validated itself. But Fisher had forgotten the exact lesson he had learned during his years promoting controlled trials: women with breast cancer deserved to know everything the scientists themselves were learning.

In 1997, the federal Office of Research Integrity exonerated Fisher and he was restored as head of the NSABP. The University of Pittsburgh apologized to him. Fisher went on to do other important research, including a study showing that the anti-estrogen pill tamoxifen can lower the rates of breast cancer among high-risk women.

Today, medicine relies almost exclusively on randomized controlled trials and their more sophisticated cousins, meta-analyses, to guide treatment decisions. Bernard Fisher’s story reminds us of the consequences patients faced in a time before such trials were the gold standard.