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The surgeon who challenged the breast ca paradigm

The surgeon who challenged the breast ca paradigm

ABSTRACT: Research led to groundbreaking breast cancer clinical trials

Bernard Fisher, MD received his medical degree in 1943 from the University of Pittsburgh SchooBernard Fisher, MDl of Medicine. As a young doctor, he was torn between a life in the operating room and one in the research lab. His curiosity about the biology of the diseases that were being treated by surgery eventually led to his decision to combine those interests.


Dr. Fisher graciously made time in his schedule to talk with ONI about his life in science. The interview started in his office at the University of Pittsburgh Medical Center, where he is Distinguished Service Professor of Surgery. From the start he made it clear: “To know me is to know my work.” But ONI also wanted to know the early influences and career choices that ultimately led to his pioneering breast cancer studies.


At about the time that Dr. Fisher began his medical studies, his great-uncle, a physiologist and surgeon who had previously taught at Vanderbilt and Western Reserve Universities, moved to the University of Pittsburgh to create a lab to develop an adrenal cortical extract for treatment of Addison’s disease.


“I got my first taste of lab work there, while I was a medical student. They would get big containers of adrenal glands from the slaughterhouse, and one of my jobs was to remove the medullas from those glands,” Dr. Fisher said.


At the same time, he said, “I discovered that either radical or super-radical surgery was the only cure for many disorders and that the operating room was where the real drama of medicine took place. Consequently, I decided to become a surgeon.”


During his surgical residency, he said, “I began to realize that the basis for many of the operations that I was performing was questionable. I realized the need for a greater understanding of the biology of the diseases that I was treating.”


Thus, Dr. Fisher was determined to participate in what was, at that time, one of the few surgical research programs in the country—the one at the University of Pennsylvania’s Harrison Department of Surgical Research. He convinced Dr. I. S. Ravdin, then chairman of the Department of Surgery at Penn, and a former brigadier general who had operated on President Eisenhower, to offer him a research position.


“I was a board-certified surgeon,” Dr. Fisher said, “but I still fed the rats on weekends. I developed a surgical technique to cannulate bile ducts in animals, keeping them alive for weeks, as part of my effort to learn more about liver regeneration.”


When his tenure at Penn ended, Dr. Fisher returned to the University of Pittsburgh School of Medicine, where he created the Laboratory of Sur-gical Research. “I had only a small stipend to live on, but I was happy. It was my lab, and I was given the opportunity to do as I pleased,” he commented.


Dr. Fisher said that his early years in the lab, beginning in 1952, comprised three distinct areas of investigation: his “Promethean Period” (liver regeneration), his “Blue Period” (hypothermia), and his “Chimeric Period” (transplantation biology). At that time, he said, he had no interest in breast cancer research.


The National Surgical Adjuvant Breast Project

In 1957 Dr. Ravdin, who chaired an NIH panel on cancer chemotherapy, invited Dr. Fisher and Career Highlightsseveral other surgeons to Stone House on the NIH campus to discuss the creation of a new clinical trials program, the Surgical Adjuvant Chemotherapy Breast Project, which was to be headquartered at Roswell Park Cancer Institute in Buffalo, New York.


Dr. Fisher said, “At that time it was thought that surgeons were responsible for the failure to cure more patients because they disseminated tumor cells during cancer surgery.”


It was believed that the use of perioperative chemotherapy, ie, during surgery and for 2 days afterward, would destroy such cells. In order to test that concept, the Breast Project group initiated its first trial, a randomized study of radical mastectomy with or without thiotepa, and enrolled its first patient in 1958.


“Those early study findings piqued my interest in how tumors metastasized and stimulated my interest in clinical trials, a process that was just being introduced as a mechanism for hypothesis-testing,” Dr. Fisher said. “The thiotepa study demonstrated, for the first time, that the natural history of some patients with breast cancer could be altered.”


In 1967, after serving as head of the executive committee of the Surgical Adjuvant Chemotherapy Breast Project (the group subsequently became known as the NSABP), Dr. Fisher was appointed chairman. At that time, interest in the group was lagging, and a new cohesiveness was needed. So, in 1970, he centralized the operations and biostatistical centers by moving them from Roswell Park to the University of Pittsburgh.



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