Isaac Craig Henderson, MD, passed away at the age of 81 at his home in San Francisco on December 26, 2022, after a brief illness. Dr. Henderson was an internationally known medical oncologist who specialized in breast cancer, beginning his career at Harvard’s then-designated Sidney Farber Cancer Institute (now the Dana-Farber Cancer Institute; DFCI) in Boston. He made substantial conceptual and leadership contributions to the translational and clinical research, evaluation, and treatment of this disease over the past 5 decades.
Isaac Craig Henderson, MD
Professional Training and Experience
Dr. Henderson received his undergraduate degree in history and chemistry from Grinnell College in Iowa in 1963, for which he later served on the Board of Trustees and by which he was honored with an Alumni Award and an honorary Doctor of Science for his accomplishments. He received his MD degree (1970) and completed his residency in internal medicine at Columbia University in New York City and served a postdoctoral laboratory fellowship at the U.S. National Institute of Health. He completed a fellowship in medical oncology at the DFCI and joined the faculty there, where he was Director of the Breast Evaluation Center for more than a decade. In 1992, he became Chief of the Division of Medical Oncology and Deputy Director of the Cancer Center at the University of California San Francisco (UCSF). With his long-time colleague, Dr. Joe Gray, he was the inaugural Co-Director of one of the first five Specialized Programs of Research Excellence (SPORE) in breast cancer. The UCSF SPORE has now been renewed through 14 continuous 5-year cycles. He was Adjunct Professor of Medicine at UCSF until his death.
Dr. Henderson left academia to join the health care industry, initially as Chief Executive Officer and Chair of the Board of Directors of SEQUUS, and subsequently with ALZA, and then with ACCESS Oncology Inc. (merged later with Keryx Biopharmaceuticals), and PrognosDx Health.
Legacy in Breast Cancer
Dr. Henderson had a substantial impact on the field of oncology in general and breast cancer specifically. He cared deeply about teaching and providing compassionate and evidence-based therapy. While at DFCI, he initiated one of the first, if not the first, multidisciplinary clinics and tumor boards in oncology, a model that is now the standard for almost all clinical cancer centers.
As a leader in two different academic institutions, Chair of the Breast Committee of the Cancer and Leukemia Group B (now designated the Alliance), and in his roles in industry, Dr. Henderson led several groundbreaking clinical trials that introduced new chemotherapies, as well as innovative schedules and doses of chemotherapy, into the treatment of patients with breast cancer.1-3 In the late 1980s, he raised red flags of concern about the widespread application of very high doses of chemotherapy followed by autologous bone marrow transplant to patients with breast cancer. His concerns were unpopular with many of his colleagues, as this approach had been rapidly adopted in clinical centers throughout the United States in the absence of randomized trial data to support it. Ultimately, his cautionary notes were proven correct by results from a trial he oversaw in CALGB,3 as well as by results from several other trials reported at roughly the same time. He also led one of the seminal trials demonstrating the benefit of adjuvant paclitaxel.2
Of note, while leading the CALGB Breast Committee, he was one of the first academic leaders to embrace patient advocates as partners in health-care research, which is now universally embraced. As Chief Executive Officer of SEQUUS, he was responsible for the introduction of liposomal doxorubicin, a substantially safer, but still effective, preparation of doxorubicin, a widely used agent for breast and ovarian cancers.4-6
Dr. Henderson believed strongly that physicians have a humanistic side, teaching medical students and young doctors that they “should have an intense interest in all things human, including emotions, so they can appreciate their patients’ subjective responses to treatment.” He lived what he taught, having spent 2 years in India on a Fulbright Scholarship. He was also a devotee of opera and served on the Board of Directors of the San Francisco Opera as well as providing medical advice to many of the cast members for several years.
Dr. Henderson was considered a widely recognized scholar and authority on cancer in general and especially breast cancer, with more than 300 publications to his credit. He was notable for insisting on both respect of the history of medicine and adoption of scientifically rigorous, evidence-based clinical recommendations. Early in his career, he coauthored, with Dr. George Canellos, a landmark review of breast cancer7,8 and subsequently several other reviews that had a huge impact on the perspective of the disease and the scientific approach the community has toward it.
His command of the literature and expertise regarding breast cancer, and oncology in general, were reflected in his many roles leading regulatory and guideline bodies that oversee the use of new drugs and approaches in cancer. He chaired the World Health Organization’s Expert Committee on the Selection and Use of Essential Medicines as well as the Oncology Drug Advisory Committee of the U.S. Food and Drug Administration. He served two terms on the Medicare Coverage Advisory Committee and was a long-standing member of the Blue Cross/Blue Shield National Association’s Medical Advisory Panel.
During Dr. Henderson’s 50+ year career, overall mortality from breast cancer has declined dramatically as a result of prospective randomized clinical trials for screening and treatment. Dr. Henderson and collaborators initiated the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG, also called the Oxford Breast Cancer Overview), which confirmed, through pooling and analysis of individual patient data from nearly every separate clinical trial of early breast cancer conducted in the world, the benefits of surgery, radiation, and adjuvant systemic therapies. Dr. Henderson served as the first Clinical Co-Chair of the EBCTCG from 1985 until 1995. The EBCTCG has published several publications in the highest regarded medical journals in the world (The Lancet and The New England Journal of Medicine), resulting in remarkable improvements in the lives of millions of patients with breast cancer worldwide.
Dr. Henderson was responsible for teaching and mentoring a generation of medical oncologists about breast cancer, and his legacy has been passed by them to subsequent generations. Indeed, he was my main mentor as I entered the field in the early 1990s, and much of what I’ve accomplished in my own career is a result of the many hours of instruction and guidance (or direct dictates!) from him. I, and so many of my colleagues, will miss him dearly.
Dr. Henderson is survived by his wife, Mary (Turner) Henderson; his son, Isaac Henderson (Christina Burns); his daughter, Amy Henderson (John Fuson); and four grandchildren.
1. Budman DR, Wood W, Henderson IC, et al: Initial findings of CALGB 8541: A dose and dose intensity trial of cyclophosphamide, doxorubicin, and 5-fluorouracil as adjuvant treatment of stage II, node+, female breast cancer. Proceedings of ASCO 11:51a, 1992.
2. Henderson IC, Berry DA, Demetri GD, et al: Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol 21:976-983, 2003.
3. Peters WP, Rosner GL, Vredenburgh JJ, et al: Prospective, randomized comparison of high-dose chemotherapy with stem-cell support versus intermediate-dose chemotherapy after surgery and adjuvant chemotherapy in women with high-risk primary breast cancer: A report of CALGB 9082, SWOG 9114, and NCIC MA-13. J Clin Oncol 23:2191-2200, 2005.
4. Overmoyer B, Silverman P, Holder LW, et al: Pegylated liposomal doxorubicin and cyclophosphamide as first-line therapy for patients with metastatic or recurrent breast cancer. Clin Breast Cancer 6:150-157, 2005.
5. Keller AM, Mennel RG, Georgoulias VA, et al: Randomized phase III trial of pegylated liposomal doxorubicin versus vinorelbine or mitomycin C plus vinblastine in women with taxane-refractory advanced breast cancer. J Clin Oncol 22:3893-3901, 2004.
6. Stebbing J, Gaya A: Pegylated liposomal doxorubicin (Caelyx) in recurrent ovarian cancer. Cancer Treat Rev 28:121-125, 2002.
7. Henderson IC, Canellos GP: Cancer of the breast: The past decade (second of two parts). N Engl J Med 302:78-90, 1980.
8. Henderson IC, Canellos GP: Cancer of the breast: The past decade (first of two parts). N Engl J Med 302:17-30, 1980.
Originally published in a communication by the Early Breast Cancer Trialists’ Collaborative Group; adapted and republished with permission.