American biologist
Bernard Fisher (August 23, 1918 – October 16, 2019) was an American surgeon and a pioneer in the biology and treatment of breast cancer. He was a native of Pittsburgh. He was Chairman of the National Surgical Adjuvant Breast Project at the University of Pittsburgh School of Medicine. His work established definitively that early-stage breast cancer could be more effectively treated by lumpectomy, in combination with radiation therapy, chemotherapy, and/or hormonal therapy, than by radical mastectomy.
The oncology journal and website "OncLive" described Fisher's research as "launching the breast cancer community into the modern era" and honored him with a Giants of Cancer Care award for his work that ultimately ended the standard practice of performing the Halsted radical mastectomy, a treatment that had been in place for more than 75 years. Thanks to Fisher, notes another major oncology journal, breast-cancer survival rates have improved worldwide.
Fisher faced constant attacks from within medical ranks as he worked to disprove the efficacy of the old status quo treatment, eventually being described as "an iconoclastic figure" who brought about "far reaching changes...in the understanding of cancer and its treatment". "The Atlantic" called him "a medical hero". He was awarded the Albert Lasker Award for Clinical Medical Research in 1985 "for his pioneering studies that have led to a dramatic improvement in survival and in the quality of life for women with breast cancer."
Early life and education.
Fisher was born in Pittsburgh, Pennsylvania, the son of Anna (Miller) and Reuben Fisher. His family was Jewish. His brother, Edwin, would eventually become a pathologist, and the brothers conducted cancer research together, particularly in their early years.
He graduated from Taylor Allderdice High School in 1936 and was inducted in their alumni hall of fame in 2009.
He graduated from the medical school at the University of Pittsburgh in 1943, then completed a surgical residency.
Career.
Early surgery, research, and postgraduate study.
Fisher was named assistant professor at the University of Pittsburgh and established the laboratory of surgical research at that institution, of which he was director. Among his research interests were liver regeneration in rats, the physiologic effects of hypothermia, and transplant rejection. While engaged in research, he also performed general and vascular surgery. He was one of the first surgeons to perform kidney transplants.
From 1950 through 1952, he was a fellow in experimental surgery at the University of Pennsylvania. In 1955, he was a research fellow at the London Postgraduate Medical School at Hammersmith Hospital, where he sought to increase his knowledge about transplantation.
NSABP.
In the spring of 1957, having returned to the University of Pittsburgh, Fisher received a request from I.S. Ravdin, M.D., who had been his mentor at the University of Pennsylvania, and who at the time was Chairman of the Clinical Studies Panel of the Cancer Chemotherapy National Service Center at the National Institutes of Health (NIH). Ravdin asked Fisher to join 22 other surgeons in attending an NIH meeting to discuss the establishment of the Surgical Adjuvant Chemotherapy Breast Project, later known as the National Surgical Adjuvant Breast and Bowel Project (NSABP).
"I wasn’t the least bit interested in breast cancer", Fisher later said. "But since Dr. Ravdin was an army general who had operated on President Eisenhower, when he commanded me to attend the meeting, I did so. At the time of that first meeting in 1956, the idea of using clinical trials to obtain information, and certainly the idea of giving therapy following surgery, were novel approaches to treatment". Fisher was initially reluctant to relinquish his research on liver regeneration and transplantation and to take up the study of breast cancer and other malignant diseases, but he became intrigued by the subject of tumor metastasis. Indeed, he "was captivated", he later said, both by "the mystery of metastasis" and by "the new concept of the clinical trial".
Fisher later said that after that NIH meeting, "I discovered how little information there was related to the biology of breast cancer and what a lack of interest there was in understanding the disease. At the meeting, I learned about the need for randomized clinical trials and the use of biostatistics to obtain credible information from those trials". Giving up the liver regeneration and transplantation research in which he had been engaged, he began, along with his brother Edwin, a member of the University of Pittsburgh's pathology department, to study the biology of tumor metastasis. He would spend the next four decades studying breast cancer.
In 1958, Fisher took part in the first randomized clinical trial examining the results of systemic therapy following radical mastectomy for breast cancer. This study of more than 800 women, which was the first project to emerge from the NIH meeting, concluded that while chemotherapy involving the drug thiotepa positively affected the survival rates of premenopausal women, physicians were hesitant to begin using systemic adjuvant therapy.
Chairman of NSABP.
In a March 20, 1967, letter, Dr. Rudolf J. Noer suggested that Fisher apply for the position of chairman of the NSABP. He was officially appointed to that post on May 9 of that year. During the succeeding decades he would lead clinical trials that would result in transformative changes in the treatment of breast cancer.
Throughout the 1960s and 1970s, Fisher studied cancer biology and performed randomized clinical studies comparing the relative effectiveness of lumpectomy, total mastectomy, and lumpectomy followed by chemotherapy or radiation.
Fisher's impact on breast-cancer treatment was the subject of an August 2013 article in the Atlantic Monthly that was occasioned by his 95th birthday. "Before 1971, if you had breast cancer, chances are you'd have to get your breast cut off", the article recalled. "Surgeons had been taught one thing: radical surgery saves lives. It was Bernard Fisher who changed their minds".
"For more than the first half of the 20th century", Fisher later explained, "surgery was the only treatment for breast cancer. During that time, there was uniform agreement about breast cancer treatment. Disagreement related to whether or not surgery should be more radical. Improvements in anesthesia and blood transfusions made it possible for surgeons to perform more extensive operations". Such was the situation when Fisher began working on breast cancer. At that time, moreover, "researchers theorized that women died of breast cancer despite radical surgery because tumor cells were dislodged during the operation. It was believed that the dissemination of those cells resulted in metastasis and subsequent death".
Since the late 19th century, breast cancer had been treated with the Halsted radical mastectomy, named for its originator, Dr. William Stewart Halsted (1852–1922), a famous surgeon at Johns Hopkins Hospital. This procedure involved the removal not only of the entire breast but also the underarm lymph nodes and chest wall muscles. Such operations left women with gaping holes in their chests. The argument for this approach was "that cancer cells, originating from the breast, always passed through the lymph nodes prior to metastatic spread and, therefore, required radical surgery to remove the entire breast, underlying chest muscle, and axillary lymph nodes to halt metastasis".
For over ten years, Fisher and his research team carried out "a multitude of investigations regarding the biology of tumor metastasis". Their findings caused them to question the very theories upon which Halsted's approach had been based, and led them to formulate an alternative hypothesis. This was "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 expensive locoregional therapy was unlikely to improve survival". In other words, they believed that cancer was spread through the blood and lymph systems and that it entered these systems at an earlier stage than had previously been thought. This meant that the best way to fight breast cancer was not to perform an extensive excision of local tissue. Instead, a lumpectomy, in which only the tumor itself and a small amount of surrounding tissue are excised, would likely be just as effective and would have the added advantage of not causing disfigurement.
What Fisher introduced, in short, was an entirely new theory about the spread of breast cancer: while Halsted had posited that it spread by permeating surrounding tissues, Fisher argued that it was spread through the blood and lymph systems.
By the late 1960s, Fisher's research had established that radical mastectomy was indeed "no more effective than total mastectomy", and that a total mastectomy, in turn, was “no more effective than lumpectomy in treating breast cancer.” Fisher consequently urged his fellow breast-cancer surgeons to change their approach to the disease. Most of them resisted, however, and continued to perform radical mastectomies, and many accused Fisher and his supporters of placing women's lives at risk by not performing the radical surgery. Fisher later described the widespread resistance to his approach by the medical establishment as “extensive and often unpleasant". "For 50 years", he later recalled, “surgeons had been trained to do radical surgery. They felt that performing the lumpectomy was totally inappropriate". Hence, "my peers were my antagonists...It was difficult to get doctors to put doctors into the trials, and, as might have been anticipated, it was even more difficult to persuade women to be randomized to a study in which some of them would undergo mastectomy and others would have their breasts preserved".
Fisher's arguments received considerable positive attention in the 1970s, however, from many women's rights activists. According to women's health activist Cynthia Pearson, the “women's health movement began talking about mastectomy as one of the examples of sexism in medical care in the United States.” Fisher's ideas won the movement's support and became a political issue as well as a medical question.
Ultimately, his recommendations for breast-cancer treatment won the approval of the medical establishment. "In 1985," reported the Atlantic, "the New England Journal of Medicine published two of Fisher's studies that definitively proved" his earlier findings. His recommended approach to treating breast cancer thereafter gained universal acceptance.
Achievements.
Fisher's work fundamentally changed the understanding of breast cancer and improved and extended the lives of thousands of women. To quote the citation of his Albert Lasker Award, Fisher "demonstrated that the regional lymph nodes were not a barrier to the dissemination of tumor cells, as postulated earlier, but were routes traversed by tumor cells to gain access to the circulating bloodstream and lymphatic system. Out of this basic work on cancer metastasis came a new model for the management of breast cancer based on the premise that the disease is systemic from its inception."
Fisher was "the first to show that less-invasive lumpectomy surgery treated breast cancer just as effectively as did disfiguring radical mastectomies." He also demonstrated that postoperative systemic chemotherapy and hormonal therapy could be efficacious elements of postoperative treatments, and that it was possible to prevent breast cancer in women who are at high risk for the disease.
When Fisher began to perform research on breast cancer, "it was widely believed," he later wrote, “that patients with tumors in the inner quadrants of the breast had a poorer prognosis than those with lesions in the outer quadrants". Fisher's research led him to conclude, on the contrary, "that the location of a tumor was unrelated to its prognosis" and "that there was no justification for selecting specific surgical or radiation approaches based upon tumor location".
Fisher discovered "that breast cancer metastasis is not solely determined by anatomic considerations, but is also influenced by biologic activity of both the tumor and the host". Furthermore, a 20-year follow-up from one of his studies proved that "lumpectomy preserved the breast with no deleterious effect on either distant disease-free survival or overall survival". Additionally, his work "provid[ed] evidence that breast cancer can be both treated and prevented".
He was the first scientist to reject the idea that cancer was "autonomous of its host," and to argue that “solid tumors such as breast cancer are likely to be systemic at the time of diagnosis and represent potential metastases during the life of the host."
In addition, Fisher carried out "the first women's health trial in the United States to evaluate the use of the preventative agent tamoxifen, which was ultimately shown to reduce by almost 50% the incidence of disease in at-risk women." The drug is now taken by millions of women who have had breast-cancer surgery.
Aside from utterly transforming the treatment of breast cancer, Fisher's pioneering of "the multicenter randomized clinical trial set a standard for the