Albert C. Broders' paradigm shifts involving the prognostication and definition of cancer.

CONTEXT: In the 19th and early 20th centuries, cancer was defined by the demonstration of invasion and metastases, based upon gross findings at surgery or autopsy. Although histopathologic examination of tumors became possible with greater and greater resolution over time, the definition of cancer remained the same. Tumors with features suggesting the biological "potential" to invade and metastasize were not cancers until they had achieved their potential. Prognostication based upon histopathologic analyses of tumor biopsies and resection specimens was not possible, as the concepts of tumor grading and staging did not exist until the 1920s and 1930s, respectively. OBJECTIVE: To examine the history of tumor grading and the concept of "carcinoma in situ" and to explore the role of Albert C. Broders, MD, and others in these discoveries. DESIGN: To address these topics, standard historiographic methods were used to examine available primary and secondary historical sources. RESULTS: Early in his career, Broders described tumor grading, showing for the first time that histopathologic findings could independently predict prognosis. This discovery quickly begat tumor staging and eventually the whole predictive biomarker field. Later in his career, Broders described carcinoma in situ, thereby changing the very definition of cancer. CONCLUSION: Historians recognize that science progresses through a series of paradigm shifts. Most clinician-scientists, even those at the very top of their fields, never make a discovery so dramatic that it changes their field forever. In the 1920s and 1930s, Albert C. Broders published 2 observations that forever changed cancer diagnosis, prognostication, and treatment.