HISTORICAL CONTEXT

There has long been an appreciation that when cancer spreads, the secondary sites colonized are more or less predictable; however, each cancer type displays different predilections. The presence of cancer in both a primary site (e.g., breast) and elsewhere (e.g., nodes or lungs) and the appreciation that these were pathologically linked was accurately recorded in the seventeenth century. In 1829, Joseph Recamier, a gynecologist in Paris, recognized the discontiguous dissemination of cancer. He described the invasion of veins and distant metastases in the brain of a breast cancer patient but did not realize that it was cancer cells that were spreading the malignant disease. The surgeon James Paget wrote that there was no need to invoke corpuscles or germs to explain the spread of cancer, and that “an unformed cancerous blastema” must be assumed when dissemination occurred in organs beyond the lungs in the course of the circulation [1].

Most famous of all are the observations of James Paget's son Stephen, who took up the challenge to answer the question, “What is it that decides what organ shall suffer in a case of disseminated cancer?” in an article published in the Lancet in 1889 [2]. Based on his own observations on the nonrandom distribution of secondary growths in breast cancer patients, and those of Fuchs and Cohnheim, who both proposed that different organs exhibited either “diminished resistance” or “predisposition” to the growth of disseminated cancer cells, Paget formalized the “seed and soil” hypothesis.