With the death of Bernard Fisher, MD, on October 16, 2019, at the age of 101, we lost a visionary thinker and medical pioneer in cancer research and care. Fisher, a surgeon and clinical trialist, revolutionized breast cancer treatment, leading trials that transformed breast cancer treatment from reliance on radical mastectomy to a focus on minimal surgery, and strategic use of systemic therapy.
Fisher was a native of Pittsburgh, one of two sons of Anna and Reuben Fisher. He and his brother, Edwin Fisher, a pathologist and close scientific collaborator, grew up in the Squirrel Hill neighborhood of Pittsburgh and graduated from the legendary Taylor-Allderdice High School. The first in his family to go to college, Fisher graduated from the University of Pittsburgh in 1940 and received his MD from University of Pittsburgh (Pittsburgh, PA) in 1943. He received a medical deferment from military service and began an internship at Mercy Hospital. Upon completion of his clinical training, Fisher turned irrevocably to a career in medical research, spending his entire career in Pittsburgh save a few early years in training at the University of Pennsylvania (Philadelphia, PA) and in London. Appointed to the faculty of the Department of Surgery at the University of Pittsburgh, he established the Laboratory of Surgical Research in 1953. Much of his early work was in the field of transplantation biology and liver regeneration; indeed, Fisher is credited with performing the first kidney transplant in Pittsburgh in 1964.
An invitation in 1958 to attend a NIH meeting to create a group for conducting clinical trials in breast and colon cancers led Fisher to shift his research focus from the normal physiology of liver regeneration to malignancy and its treatment. As he recounted in his David A. Karnofsky Memorial Lecture in 1980, his preclinical studies over the next decade were “…directed toward a better understanding of metastatic mechanisms, (and) dispelled many of the popularly held hypotheses regarding tumor cell dissemination” (Fisher, Cancer Res 1980;40:3863–74). These insights were translated into a series of elegant clinical trials that systematically moved the field away from a belief in the importance of radical surgery in treating breast cancer as a disease that spreads in an orderly anatomic fashion to the recognition that breast cancer is frequently a systemic disease at the time of diagnosis. As a founder of the National Surgical Adjuvant Breast and Bowel Project (NSABP), Fisher became chairman in 1967 and oversaw a series of meticulously designed and executed clinical trials that moved breast surgery from the age of radical mastectomy to the modern era of lumpectomy plus radiotherapy, with similar outcomes. Sequential NSABP trials also helped to define the role of adjuvant and neoadjuvant chemotherapy, adjuvant endocrine therapy with tamoxifen and later aromatase inhibitors, and anti-HER2 therapy for the treatment of early breast cancer. The NSABP also published the pivotal trials on tamoxifen as a prevention agent for high-risk women, leading to the first approval by the FDA of a drug to reduce the risk of developing breast cancer. It is a certainty that 60 years of trials like those conducted by the NSABP combined with screening to promote early detection have contributed to the 40% reduction in breast cancer–related mortality in the United States since 1990 and helped to shape treatment algorithms for virtually all women (and men) with early breast cancer.
Those who knew him will agree that Fisher was a force of nature. He was driven, focused, and relentless in his pursuit of evidence-based therapy. He successfully challenged the prevailing surgical dogma dating back to Halsted in the 19th century. He was visionary and charismatic in his ability to assemble a national consortium of surgeons and medical and radiation oncologists who performed NSABP trials at centers, large and small, across the United States. He helped to infuse the cancer medical specialties with their focus on clinical investigation to improve patient outcomes, which prevails even today.
But Fisher's career was not without challenges. From 1994–1997 he and his work were at the center of a catastrophic battle over scientific fraud emanating from a small number of cases among the many thousands of women enrolled in NSABP trials. A Congressional review process threatened to discredit Fisher and cast doubt on the validity of the clinical trial data on which so many patients and physicians relied. Fisher was removed from his leadership position at NSABP by the NCI and the University of Pittsburgh and his articles were transiently labeled as potentially tainted by scientific misconduct by the NIH. Subsequent analyses that excluded the fraudulent data confirmed the original conclusions. Never one to back down when he believed he was right, Fisher sued the NCI and the University of Pittsburgh and received an apology and a $2.75 million settlement in 1997. He retained his title of Distinguished Service Professor at the University of Pittsburgh, a position he held until his death.
As a breast cancer researcher, I started my career when Fisher was already a powerful force and an intimidating figure for a novice in the field like me. I became better acquainted with Fisher when I became Director of the University of Pittsburgh Cancer Institute in 2009. Within weeks after my arrival, I was honored to deliver the Bernard Fisher Lecture at the University of Pittsburgh with Fisher in the audience. This happy event was the nexus for a University-wide celebration of Fisher's 90th birthday. All the leaders of the University and NSABP and Fisher's family came together that day to surprise Fisher with the conferral of an honorary degree in recognition of his many contributions. For once in his career, Fisher was near speechless.
Of course, this local remembrance was but one of the many honors that Fisher received. He was elected to the National Academy of Medicine and served as President of the American Society of Clinical Oncology from 1992–1993. He won the 1985 Albert Lasker Clinical Medical Research Award, the 1993 General Motors Cancer Research Foundation's Kettering Prize, the 2003 Medallion for Scientific Achievement from the American Surgical Association, and the 1986 American Cancer Society Medal of Honor.
No remembrance of Fisher would be complete without recognizing his nearly 70-year marriage to Shirley (Kruman) Fisher who left her career as a bacteriologist to marry Fisher and provided lifelong support for his research and personal life until her death in 2016. Her unique combination of grace, steeliness, and unwavering commitment was undoubtedly the key to Fisher's success. The Fishers are survived by three children—Beth Fisher, Joseph Fisher, and Louisa Rudolph, five grandchildren and two great-grandchildren.
A son of Pittsburgh and a man of steel, Fisher was multifaceted in his interests and strengths. I learned this personally when I met with Fisher as part of my recruitment to the University of Pittsburgh. Fisher hosted the interview in his office and archives at the University of Pittsburgh, a vast and impressive space that truly enshrined the history of breast cancer in records and files of Fisher's hundreds of articles addressing breast cancer over the 20th century. But much more touching and influential was a letter that I received from Fisher some days later, in which Fisher enclosed a copy of the poem “Ithaka” by the modern Greek poet, Cavafy, with a note that he had found it helpful as he faced some of the decisions of his life.
This poem reads in part:
“As you set out for Ithaka hope your road is a long one, full of adventure, full of discovery. …. Keep Ithaka always in your mind. Arriving there is what you're destined for. But don't hurry the journey at all. Better if it lasts for years, so you're old by the time you reach the island, wealthy with all you've gained on the way, not expecting Ithaka to make you rich. Ithaka gave you the marvelous journey.”
As Cafavy advised, Bernard Fisher's journey was long, adventurous, and full of discovery. And we are all far richer because of that journey.