Bernard Fisher, pioneering breast cancer researcher, dies at 101

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Bernard Fisher, a surgeon and clinical trialist who revolutionized the field of breast cancer research and all but eliminated reliance on disfiguring surgeries, died Oct. 16 at the age of 101.

At the time of his death, Fisher was the Distinguished Service Professor at the University of Pittsburgh School of Medicine.

“The world has lost a great man. Dr. Bernard Fisher, a courageous surgeon who almost single-handedly, over great resistance, changed the paradigm of breast cancer treatment from brutish to the more compassionate and successful treatment of today leading to reduction in mortality and morbidity,” Vincent DeVita, a former NCI Director and the Amy and Joseph Perella Professor of Medicine and Professor of Epidemiology and Public Health at the Yale School of Medicine, wrote on Facebook. “And I have lost a great friend. Rest well Bernie. There is a very large chorus of angels waiting for you.”

Fisher was a Pittsburgh native, born to Anna and Reuben Fisher.

He earned a Bachelor of Science in 1940 and an MD in 1943 at the University of Pittsburgh. Following training as a surgeon, he joined the Pitt faculty as its first full-time member of the Department of Surgery. In 1953, he established the first Laboratory of Surgical Research at the University.

Early in his career, Fisher contributed to the development of both transplantation and vascular surgery, performing the first kidney transplant in Pittsburgh in 1964 and directing surgical research at Pitt in liver regeneration, transplant rejection, and hypothermia.

The focus of Fisher’s career shifted shifted in 1958, when his mentor from the University of Pennsylvania, General I.S. Ravdin, invited him to attend an NIH meeting that would create a group for conducting clinical trials on breast and colon cancers. Ravdin chaired the NIH Clinical Studies Panel.

After that meeting, Fisher became a founding member of the National Surgical Adjuvant Breast and Bowel Project. He served as the chairman of NSABP from 1967 to 1994.

Based on research conducted in his laboratory at Pitt, Fisher formulated hypotheses that led him to challenge breast cancer treatment dogma that had prevailed since the 19th century—that patients were best treated with radical mastectomy. These hypotheses were tested in clinical trials that he directed with the NSABP in the 1960s and 1970s.

In 1971, Fisher led the NSABP in a landmark clinical trial in women with primary breast cancer, comparing radical mastectomy with less extensive total mastectomy. In 1976, he initiated a study comparing total mastectomy with less disfiguring lumpectomy, with or without breast irradiation. Neither study showed a survival advantage from the more extensive procedure. Those studies provided a scientific basis for less extensive surgery.

Findings from other Fisher-led studies showed that the addition of systemic, adjuvant chemotherapy or hormonal therapy provided a survival advantage over surgery alone. Based on these studies, Fisher and the NSABP initiated the first trial to test tamoxifen as a breast cancer prevention agent in 1992. That trial showed that tamoxifen decreased the incidence of breast cancer and was appropriate for many women at increased risk for the disease.

“Our 1998 report indicating, for the first time, that breast cancer could be prevented with tamoxifen was probably the capstone of my career,” Fisher said to Pitt Med Magazine last year, at age 100. “Certainly, in 1958, when I began this journey, the idea of using an agent to try to prevent breast cancer was . . . .”

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Fisher’s career—and his legacy—were nearly destroyed in 1994, after Rep. John Dingell (D-MI) started an investigation stemming from an incident of scientific fraud at a Canadian site of NSABP.

In the course of this scandal, Fisher was fired by NCI as chair of NSABP and set adrift by Pitt (The Cancer Letter, April 22, 1994). Subsequently, the cooperative group narrowly escaped being dissolved. Though Dingell’s committee liked nothing more than a sincere televised mea culpa from a perp, Fisher refused to apologize.

Scientific fraud occurs sometimes, but in this case it was truly minimal, and it didn’t affect the overall findings.

After years of litigation against NCI, the university, and the law firm of Hogan & Hartson, Fisher received an apology and a check for $2.75 million (The Cancer Letter, Sept. 5, 1997).

“The University of Pittsburgh wishes to take this opportunity to apologize to Dr. Fisher and express its sincere regret at any harm or public embarrassment that Dr. Fisher sustained which was in any manner related to the activities of the University of Pittsburgh, and/or its employees,” Pitt and Fisher said in a joint statement. “The University and Dr. Fisher wish to affirm that at no time was Dr. Fisher found to have engaged in any scientific or ethical misconduct concerning any of his work.

“The University’s acceding to the National Cancer Institute’s decision in the spring of 1994 to remove Dr. Fisher as principal investigator of the NSABP and the subsequent developments in the now settled litigation reaffirms the necessity of the university’s commitment to fully investigate any allegations against faculty members which leave the potential to impinge upon their First Amendment rights or the essential rights and freedoms of the academic community.”

NCI, which contributed a $300,000 settlement to cover a portion of Fisher’s legal expenses, also issued a statement that included this list of Fisher’s contributions to science:

  • Showing that, for treatment of breast cancer, lumpectomy plus radiation provides the same surgical benefit as the radical, disfiguring Halsted mastectomy or modified radical mastectomy, while permitting conservation of the breast.

  • Demonstrating that when used as an adjuvant therapy, tamoxifen, a hormonal treatment, improved survival of women with early stage breast cancer. Combined with his studies of adjuvant chemotherapy, this work led NCI to state that all women with early stage breast cancer should consider adjuvant therapy (either hormones or chemotherapy) to improve their survival. His research on tamoxifen also showed that five years of tamoxifen therapy is as good as longer courses of treatment.

  • Showing that neoadjuvant chemotherapy (chemotherapy before surgery) can safely permit some women with large breast tumors to choose lumpectomy plus radiation instead of mastectomy. He also showed that chemotherapy plus tamoxifen improves survival for early stage, node-positive breast cancer patients when it was compared to tamoxifen alone in both premenopausal and postmenopausal women.

  • Initiating the Breast Cancer Prevention Trial, a study of tamoxifen in the prevention of breast cancer, which recently completed accrual of over 13,000 women.

  • Convincing his medical colleagues of the importance of clinical research and that clinical studies could be carried out at the community level.

Fisher, too, got to rejoice.

“Much of what happened was due to this lack of understanding at all levels—government, public, university,” he said to The Cancer Letter at the time. “If something didn’t seem to be logical to them, then it was wrong. I am glad to be alive to see this vindication.

“That, to me, is an emotional experience, because so many people have died, and then it was some time later for their vindication to appear. From that standpoint, I am very fortunate.”

Fisher 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 of the American Surgical Association, the Bristol-Myers Squibb Award for Distinguished Achievement in Cancer Research, the 1986 American Cancer Society Medal of Honor, and the Sheen Lifetime Achievement Award of the American College of Surgeons.

“All of oncology owes an enormous debt of gratitude to the contributions of Bernard Fisher,” Norman Wolmark, a surgeon who replaced Fisher as the NSABP chair and who now serves as professor of surgery at the University of Pittsburgh School of Medicine, said in a statement. “He instilled in us the passion for the randomized prospective clinical trial as a vehicle to define optimum therapy in the treatment of breast cancer and other solid tumors applying the scientific method.

“He delivered us from the age of tyranny when a single individual could dictate the therapy of a particular disease based on his own biased retrospective experience. In the process, Bernard Fisher revolutionized our understanding of the biology of breast cancer. His seminal work has saved countless patient lives and has had an immeasurable effect in allaying suffering. I have lost a mentor, colleague and friend, and the field of oncology has lost its noblest protagonist,” Wolmark said.

Fisher is survived by three children, Beth Fisher, Joseph Fisher, and Louisa Rudolph, five grandchildren and two great-grandchildren.

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