Dr. Bernard Fisher - a Pioneer who Helped Change the Way Breast Cancer is Treated
Dr. Bernard Fisher graduated from University of Pittsburgh Medical School in 1946. He first started a a laboratory to investigate liver regeneration and transplant. In 1957 he attended a meeting of 23 surgeons at the NIH, which would lead to the formation of the National Surgical Adjuvant Breast and Bowel Project (NSABP). The first NSABP patient was randomized in 1958 in a trial to determine the effectiveness of adjuvant chemotherapy in early stage breast cancer. This first trial offered proof-of-concept that large randomized clinical trials following rigid criteria could be conducted at multiple sites across the country. In 1967 Fisher became the chair of the NSABP, a role he would occupy for nearly 30 years.
The prevailing orthodoxy in breast cancer treatment well into the 1960’s was based on the Halsted hypothesis, which stated that tumors spread in an orderly defined manner from primary site to regional lymph nodes and then to distant sites. This lead to the treatment of breast cancer by radical surgery. The Halsted or radical mastectomy is an en-bloc resection of the breast with pectoralis major and minor muscles as well as the axillary contents and was the standard treatment for breast cancer for nearly 100 years - from the late 1800’s through the 1970’s.
As a result of extensive laboratory investigations into the biology of tumor metastases conducted in the 1950’s and 60’s, Fisher formulated a new hypothesis, which he stated was “not the result of either conjecture, impression or reinterpretation of findings reported by others” and since many of its tenets were contrary to those of Halsted, it was designated the “alternative hypothesis.” The implications of the Fisher or alternative hypothesis are that breast cancer may be regarded as a systemic disease at the time of diagnosis and that the extent of surgery and local therapy are unlikely to make significant differences in outcomes.
Two landmark trials, NSABP protocols B-04 and B-06, were implemented in 1971 and 1976 respectively. These trials served to establish the efficacy of breast conserving surgery and to validate the alternative hypothesis. Protocol B-04 showed no survival advantage for radical mastectomy compared to total mastectomy with or without radiation, with 25 year follow-up reported in 2002. Protocol B-06 was designed to evaluate the efficacy of further minimal surgery. Total mastectomy showed no survival advantage over lumpectomy with or without radiation, with 20 year follow-up reported in 2002.
The Fisher hypothesis which was validated in these landmark clinical trials has lead to the rise of breast conserving surgery and the inextricable link to systemic adjuvant chemo and hormonal therapy. Fisher has spent the later part of his career defending the accuracy of his work. He celebrated his 100th birthday August 23, 2018.
References:
1. Fisher B, Anderson SJ: The breast cancer alternative hypothesis: is there evidence to justify replacing it? J Clin Oncol 28:366-374,2010
2. Cavalo J: Dr. Bernard Fisher’s Breast Cancer Research Left a Lasting Legacy of Improved Therapeutic Efficacy and Survival. The ASCO Post: May 15, 2013
3. NSABP Foundation website
4. Fisher B, et. al.: Twenty five year follow-up of a randomized trial comparing radical mastectomy, total mastectomy, and total mastectomy followed by irradiation. N Engl J Med 347:567-575, 2002
5. Fisher B, et. Al.: Twenty year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med 347: 1233-1241, 2002