Last week, we discussed the origins of the Halsted radical mastectomy and its prominence and success in the treatment of localized breast cancer. Let us now return to Bernie Fisher. After finishing training as a surgeon and joining the faculty at the University of Pittsburgh, he started his career as a liver researcher. In 1957, he was invited to a meeting on breast cancer at the NIH and recognized how little was understood about the biology of breast cancer. This led him to shift his research interests and, working with his brother Edwin, a pathologist at the University of Pittsburgh, they began to study breast cancer biology in rodents.
The success of the Halsted radical mastectomy brought it much loyalty in the surgical establishment. When Fisher appeared on the scene, his and Edwin’s laboratory studies suggested that the underlying hypotheses that justified the radical mastectomy were not correct. Their research suggested that breast cancer cells spread and metastasized in irregular ways and not in a systematic progression (tumor to axilla to regional tissue to muscle, etc.) but could spread early on directly to blood or not. Thus, whether extreme radical surgeries or more limited ones were performed would not necessarily alter the outcomes.
The meeting he attended in 1957 led to the formation of the National Surgical Adjuvant Breast Project (NSABP), a group whose aim would be to conduct randomized trials to advance knowledge in breast cancer. What was unusual was that it was the first time that surgeons would be involved in clinical trials, and that randomized trials would be utilized to answer questions regarding surgical issues. Initially Fisher served as head of the University of Pittsburgh site, but in 1967 he was appointed to be chair of the overall NSABP, a position he retained until 1994.
This led to his first major achievement, a paper published in 1977 in the journal Cancer. I quote the first two sentences: “There has existed great controversy concerning the treatment of primary breast cancer. Prompted by that uncertainty, the National Surgical Adjuvant Breast Project (NSABP), after almost a decade of planning initiated in August of 1971 a prospective clinical trial to compare the worth of alternative treatments with radical mastectomy.” The trial compared the Halsted radical mastectomy to total mastectomy (the same procedure but leaving intact the axillary lymph nodes and pectoralis muscles). A third group of subjects received a total mastectomy with radiotherapy. I cite this quote from the paper so the reader can read between the lines how much controversy and dissension this study generated—it took 10 years of discussion, planning and cajoling before the multiple surgeons and surgical groups could agree to undertake this study. Many saw it as unethical and dangerous to their patients. Many refused to participate, and Fisher was forced to go to various Canadian institutions to enroll enough patients in order to conduct the study.
Ultimately, over 1,700 women with localized breast cancer were randomized among the three arms of the study between 1971 and 1974. After three years of follow-up, the recurrence rates were almost identical across the three groups, roughly 20% for those with clinically negative lymph nodes, and 37% for those with clinically positive nodes. Fisher and his co-authors concluded that there was no harm in leaving the axillary nodes and the pectoralis muscles in place at the time of surgery. This study had a profound effect on how breast cancer surgery was subsequently performed in the U.S., essentially tolling a death knell for the radical mastectomy and a switch to what became known as the modified radical mastectomy (a variation on total mastectomy). It was an extraordinary achievement.
In the meantime, there was accumulating anecdotal evidence that even more limited surgery could also be effective in treating localized breast cancer. There were no trials of these procedures and they mostly occurred when patients refused more extensive surgery. A famous example was Babette Rosmond, a New York City writer, who in 1972 refused a radical mastectomy for her localized breast cancer. She insisted on a biopsy and, when it was positive, she was told by the surgeon that if she did not have a radical mastectomy she could possibly die within three weeks (obviously a little hyperbolic!). Instead, she went searching for a surgeon who would agree to do a limited procedure. It was not easy to find one, but ultimately she found Barney Crile, a breast surgeon at the Cleveland Clinic, who did what we now call a lumpectomy; he later became a major advocate of alternative surgical procedures. She died in 1997 at the age of 80, disease-free.
Multiple similar situations occurred. Aside from some interest in limited or breast conserving surgery, these anecdotes also led to a movement towards preoperative biopsies prior to surgical decision-making. This was particularly opportune since the use of screening mammography was now arising so that biopsies were more and more necessary for that purpose as well.
In the next episode of “Thoughts on Cancer,” we will discuss how Bernie Fisher moved the breast surgery world to an even more revolutionary level.
Alfred I. Neugut, MD, PhD, is a medical oncologist and cancer epidemiologist at Columbia University Irving Medical Center/New York Presbyterian and Mailman School of Public Health in New York.
This article is for educational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment, and does not constitute medical or other professional advice. Always seek the advice of your qualified health provider with any questions you may have regarding a medical condition or treatment.
