NCI’s Hoover Retires, Leaving Legacy of Epidemiology Research

In June, Dr. Robert N. Hoover, director of the Epidemiology and Biostatistics Program, retired from the Division of Cancer Epidemiology and Genetics (DCEG) after 48 years of service to the National Cancer Institute.

He is widely known as an international leader in cancer epidemiology and expert in hormonal carcinogenesis, a visionary scientist who established multiple ongoing programs of research to understand the causes of cancer in human populations, as well as a generous mentor of scores of trainees. 

Through his years of leadership at NCI, Hoover and Dr. Joseph Fraumeni, Jr., DCEG founding director and scientist emeritus, nurtured what began as a small branch into a large and diverse division that is recognized worldwide as the premier research program in cancer epidemiology. “From the beginning, Bob has been the quarterback of the epidemiology program at the NCI, serving as the driving force of the division with his dedication to uncovering the genetic and environmental causes of cancer,” said Fraumeni.

Hoover earned his B.A. from the University of Notre Dame, his M.D. from Loyola University in Chicago, and his Sc.D. in epidemiology from Harvard School of Public Health. He joined the Epidemiology Branch at NCI in 1972 as a commissioned officer in the Public Health Service. After holding a series of leadership positions, Hoover became director of the Epidemiology and Biostatistics Program when DCEG was founded in 1996.

Throughout his years of leadership, he has been particularly adept at building high-quality study resources not only for his own research, but also for the entire program through diverse collaborations across NCI and extramural organizations. 

“Although population scientists recognize Bob’s tremendous life-long contributions to cancer epidemiology, what is often underappreciated are the myriad and unique ways that Bob facilitated many of the most challenging and essential advances in cancer research from behind the scenes,” said Dr. Robert T. Croyle, director of the Division of Cancer Control and Population Sciences. “He epitomizes science for the public good, with his intellectual generosity, wisdom and a remarkable ability to navigate political and bureaucratic barriers to collaboration, scientific progress and the application of rigorous evidence to public health. As a role model, mentor, investigator and colleague, he is second to none.”

Hoover was the first to utilize the entire SEER Cancer Registry Program as a resource for large population-based case-control studies of cancer and was among the first to collaborate with health maintenance organizations to access their medical records as powerful resources for prospective studies of cancer. In the early 1990s, he worked closely with NCI’s Division of Cancer Prevention to develop the Prostate, Lung, Colorectal and Ovary Cancer Screening Trial (PLCO) into a powerful prospective observational study of all cancer sites. Its signature and unique serial collection of biospecimens and questionnaire data provided unprecedented potential for etiologic studies and the identification of biomarkers and remains a treasured resource still heavily utilized today. 

In the last 10 years, Hoover has focused on developing a new “cohort of the future,” which will soon be realized through the Connect for Cancer Prevention Study. It will feature many of the same critical design elements that are the hallmark of his visionary planning: collection of serial information and biospecimens and utilization of electronic medical records to support cutting-edge molecular epidemiology over the next several decades.

A continuing focus of his personal research, which stemmed from his thesis work, has been understanding the relationship between hormones and cancer. Some of Hoover’s contributions include the first study to identify menopausal hormone therapy as a cause of breast cancer, as well as the first to observe and establish the stronger carcinogenic effect of the combined estrogen-progestin regimen, compared with estrogen alone. These early studies were paradigm shifting, overturning then-conventional beliefs that hormones were protective against cancer.

In addition, Hoover pioneered research into the adverse effects of early-life hormonal exposures, most notably studies on women and their offspring who were exposed to diethylstilbestrol (DES). Between the early 1940s to 1970s, the first synthetic estrogen, DES, was marketed and prescribed to millions of pregnant women to prevent miscarriage and other complications of pregnancy. The association between prenatal DES exposure and vaginal and cervical cancer was established in the early 1970s and use was subsequently discontinued. However, by the late 1980s, most of the follow-up studies had progressively waned. Recognizing the need to continue observing DES-exposed mothers and their offspring, Hoover reached out to investigators at various study centers and successfully revitalized the cohorts, pooling the data to better answer the many questions that remained. 

In 1992, the combined studies were assembled and named the DES Follow-up Study, the first and only large cohort of women and offspring exposed in utero to DES. To date the study has identified 12 major adverse health outcomes in addition to vaginal cancer and is continuing follow-up work on the third generation. The DES experiment—tragic for the affected families—benefited millions by demonstrating the urgent need for post-market monitoring of prescription medications.

His interest extended to other classes of treatments as well. He conducted the first epidemiologic assessment of cancer risks associated with immunosuppressive therapy and developed a systematic series of studies of carcinogenic risks associated with various cancer therapies. These studies altered our understanding of carcinogenesis as well as leading to changes in treatment strategies.

Another central theme of Hoover’s research was development of the Cancer Atlas in 1975, which mapped mortality rates within the U.S. and internationally. While prior efforts generated only state-level mortality data, Hoover and colleagues produced county-level data that identified “hot spots” of cancer mortality—an early example of the promise of data visualization in epidemiologic research. Resultant case-control studies exploring these patterns linked lung cancer among men on the southeast Atlantic coast to their work in shipyards, and oral cancer risk among women in North Carolina to chewing tobacco. Recently, Hoover and colleagues used the same approach to connect arsenic in drinking water to the increased risk of bladder cancer in men and women in northern New England. His work has extended to other occupational and environmental exposures such as studies on groups exposed to pesticides, formaldehyde, arsenic and other agents, frequently producing findings leading to regulatory actions.

One of the pillars of Hoover’s career was his dedication to mentorship. “Aside from his exceptional talent as a scientist, he is a tremendous and generous mentor whose wisdom was sought by all—from trainees, investigators, to branch chiefs and division directors, myself included—who lined up outside his office eagerly seeking his advice,” remarked Fraumeni.

“People sought out Dr. Hoover’s advice for his epidemiologic rigor and breadth of knowledge, as well as his considerate and Socratic mentoring style of asking penetrating questions to help trainees work through their challenges,” said Dr. Patricia Hartge, scientist emerita and former deputy director of the Epidemiology and Biostatistics Program. 

Hoover has enjoyed mentoring two generations of junior investigators who have gone on to successful careers in government, academia and industry. He was recognized in 2015 by the NCI women scientist advisors with their Mentoring and Leadership Award for his exceptional dedication, leadership and tireless efforts to promote, nurture and mentor NCI women scientists at all stages of their careers.

Over the course of his career, Hoover has served NIH and the epidemiological community by providing expert assessments of epidemiologic evidence, evaluating plans and progress of scientific endeavors, sitting on search committees and advising on training programs. He has often been called upon by NCI and NIH to brief members of Congress and their staff on issues related to cancer epidemiology and science policy. He has been an advisor to many other government entities including the Food and Drug Administration, the Office of Management and Budget, the U.S. Military Cancer Institute and the Public Health Service. He has also lent his expertise to many national and international organizations including the World Health Organization, the International Agency for Research on Cancer, Union for International Cancer Control, the Danish Cancer Registry, the American Cancer Society, the General Motors Cancer Research Foundation and DES Action USA.

Hoover has received numerous honors, including the Distinguished Service Medal from the Public Health Service (1990), the Gorgas Medal from the Association of Military Surgeons of the United States (1996), the John Snow Award for Epidemiology Research from the American Public Health Association (2001), Alumni Award of Merit from the Harvard T.H. Chan School of Public Health (2002), Distinguished Achievement Award from the American Society of Preventive Oncology (2002), the Abraham Lilienfeld Award from the American College of Epidemiology (2005), HHS Secretary’s Award for Distinguished Service (2004), NIH Distinguished Investigator (2019) and numerous other awards from NIH and PHS. 

Hoover is a member of the American Epidemiological Society and the Association of American Physicians. He has contributed to more than 600 peer-reviewed publications, 32 editorials or commentaries and 45 book chapters.

“Dr. Hoover has been a major figure in shaping the field of cancer epidemiology, inspiring many others by his insight and example, while training and mentoring some of the foremost cancer epidemiologists in this country and abroad, said DCEG director Dr. Stephen Chanock. “His creative approaches to interdisciplinary studies, which utilize clinical observations and laboratory methods, have been adopted by epidemiologists throughout the world.” 

In retirement, Hoover will serve as scientist emeritus to the division.