There is some truth to the old adage that cancer is as old as the human race, but paleopathologic findings indicate that tumors existed in animals in prehistoric times, long before men appeared on Earth. Let it be what it may, ultimate reliance in history requires written records. In medicine, the earliest written description of diseases and cancer, a breast cancer, is found in the Edwin Smith Papyrus that was written approximately 3000 BC. The writer concluded that bulging tumor of the breast was a grave disease and there was no treatment for it1 (Fig. 1). The Ebers Papayrus, dated circa 1500 BC, contains the first reference to a soft‐tissue tumor, a fatty tumor, and includes reference to possible cancers of the skin, uterus, stomach, and rectum.2 The Egyptians attempted to treat tumors and cancers with cautery, knives, and salts, and introduced arsenic paste that remained in use as “Egyptian ointment” until the 19th century.3 The Sumerians, Chinese, Indians, Persians, and Hebrews of the same epoch were partial to herbal remedies such as tea, fruit juices, figs, and boiled cabbage, but in advanced cases, they did not hesitate to resort to solutions and pastes of iron, copper, sulfur, and mercury. Many of these concoctions remained in external and internal use, in various concentrations, for more than 3000 years.4, 5

Figure 1 Open in figure viewer PowerPoint The Edwin Smith Papyrus was written about 3000 BC.

The Greeks molded medicine into a mixture of art and science. Hippocrates (460‐375 BC) and his disciples opposed superstitions as cause of cancer. They believed that cancer was initiated by natural causes. They rationalized that excess or deprivation of blood, mucus, bile, and other body secretions, particularly at old age, may induce cancer. Cancerous growths reminded Hippocrates of a moving crab, which led to the terms carcinoma (malignant tumor) and cancer (ulcerated malignant tumor). Scirrhus, or hard tumor, was separated from carcinoma and cancer, and listed as a tumor with uncertain malignant potential. Greek physicians knew about cancer of the skin, mouth, stomach, and breast. Hippocrates described anorectal condylomas and polyps and used a speculum for examination if the lesion was higher up in the colon. He regarded breast cancer and cervical cancer with bloody discharge as life‐threatening tumors and applied only palliative care. Superficial and deep carcinomas and cancers were separate entities and were treated differently. Superficial lesions were treated with lotions and cautery, and deep tumors were either cut out with a knife or deemed untreatable5, 6 (Fig. 2).

Figure 2 Open in figure viewer PowerPoint The collected writings of Hippocrates was printed in Venice in 1588.

After Greece became part of the Roman Empire in 146 BC, Greek physicians were granted Roman citizenship and a place to settle in Rome. Among the new citizen‐physicians was Aulus Celsus (25 BC‐AD 50). Celsus became an influential Roman physician and made Latin the language of medicine. He continued the Hippocratic tradition by comparing cancer to a crab that adheres to surrounding structures with his claws. In his De Medicina, he described several varieties of superficial cancer, but he also mentioned cancers of visceral and parenchymal organs such as the stomach, colon, liver, and spleen.3, 4 Celsus treated superficial carcinomas with a topical application of boiled cabbage and a salted mixture of honey and egg white. For cancers, he recommended early and aggressive surgical therapy. He knew that advanced breast cancers have a tendency to recur in the armpit, with or without swelling of the arm, and may cause death by spreading to distant organs5, 7, 8 (Fig. 3).

Figure 3 Open in figure viewer PowerPoint The first edition of De Medicina by Celsus was printed in Florence in 1478. It is known as the first medical book published by printing.

Remedies for cancer were compiled by Pliny the Roman (AD 23‐79), in his Materia Medica. He recommended compound herbal and other remedies for internal use in advanced cancer before or after attempted surgery. His most highly praised prescription was a boiled mixture of ash of sea crabs, egg white, honey, and powdered feces of falcons.4

The first comprehensive description of symptoms, signs, and treatment of cancer of the uterus was rendered by Aretaeus (AD 81‐138), who lived and practiced medicine in Alexandria, Egypt. He wrote, in his notes, that there were 2 distinct forms of cancer: one was firm to the touch and nonulcerated, whereas the other was foul smelling and ulcerated. Both tumors were associated with pain and swelling in the groin. He regarded both lesions as chronic and deadly, but the ulcerated one was worse without any chance of cure. He looked upon uterine bleeding in association with enlargement of the uterus as an incurable condition4, 9 (Fig. 4).

Figure 4 Open in figure viewer PowerPoint De Acutorum by Aretaeus was published in Paris in 1559.

Aretaeus is also remembered for his clinical description of elephantiasis, jaundice, and pleurisy, as well as the first accurate account of diabetes, to which he gave its present name. The Romans' thinking about cancer, as well as the whole known world at that time, came under the influence of Claudius Galen (130‐200), a native of Greece, who practiced medicine in Rome.3, 5, 10 He believed that thick black bile caused ulcerated and incurable cancer, whereas thin yellow bile was responsible for nonulcerated and curable cancer. Despite being an appointed surgeon to the gladiators, he accepted the Roman prejudice against surgical treatment of cancer. Galen held that cancer was a disease of the sick and should be treated with purgatives to diminish the accumulation of black bile. He named swellings and fleshy tumors with the appearance of raw meat sarcoma. Galen was a prolific writer who wrote more than 100 notes on tumors and cancers, more than any of his predecessors (Fig. 5). His writings were translated from Greek into Latin and were widely distributed, in handwritten copies, in all known countries. His dogmatic theories well suited the Christian theology as well as Byzantine and Arabic teachings, and delayed advances in understanding the natural history of cancer and its treatment for several centuries.4, 5, 11

Figure 5 Open in figure viewer PowerPoint The collected writings of Galen was printed in Venice in 1625.

After the decline of the Western Roman Empire, Constantinople and Baghdad became the centers of medical knowledge, and several physicians are renown for their contributions to the advancement of medicine.5 Oribasius of Baghdad (325‐403) noted that cancers were mostly painless and were not as red as inflammatory lesions. Cutting into cancers, he observed scirrhous (firm) tissue, black bile, and coarse soft material (necrosis). He admitted that he had no luck in curing ulcerated cancers. Treatment of breast cancer by amputation of the whole breast was introduced by Aetius (527‐565), physician to Emperor Justinian in Constantinople.4, 12 He treated nonulcerated lesions of the cervix, labia, and the anus with cautery, but he offered no treatment for ulcerated cancers. He recommended complete excision of tumors of the extremities by using elliptical incision13 (Fig. 6). Thyroidectomy and nasal polypectomy were introduced by Paulus of Aegina (625‐690). He knew about cancer of the liver and the intestines. He did not hesitate to excise cancers, but he advised that surgery be avoided if the cancer was insensible because it was incurable.4

Hippocrates and Galen were introduced to the Arabic world by Rhazes of Baghdad (860‐932). He practiced surgery and introduced new operative techniques and instruments. In his De Chirurgia, he described jaundice as being caused by an obstruction of the bile duct. He relieved intestinal obstruction by surgical resection of the affected segment, but he warned surgeons that if the obstruction was caused by cancer, no surgery should be attempted unless the cancer can be excised completely.5, 13 Avicenna of Persia (980‐1037) introduced polypectomy by a wire loop that was made tighter each day until the tumor fell off14 (Fig. 7). Surgical treatment of cancer was introduced in Spain by Albucasis (1013‐1106), the first Muslim physician in Europe. He practiced bloodletting before surgery and was an advocate of ligation of vessels only in severe hemorrhage. It is perhaps not a surprise that he cautioned that extensive surgery should be used sparingly for treatment of cancer because surgery may kill the patient before the cancer does.3, 4, 15 The signs and symptoms of cancer of the esophagus were described by Avenzoar (1070‐1162). He was a Jewish physician who practiced in Cordova, Spain. He invented esophageal and gastric cannulas for relief of strictures caused by cancer and for injection of nourishment. He knew about obstruction by rectal cancer and introduced hysterectomy for removal of uterine tumors.5, 8

Figure 7 Open in figure viewer PowerPoint Avicenna's Canon of Medicine was printed in Rome in 1593.

In 1215, the Pope announced that the church abhorred bloodshed and prohibited surgical operation. However, the prohibition failed to restrain Theodoric (1205‐1296), a bishop and physician, who practiced in Salerno, Italy. He knew that cancers, particularly the neglected ones, commonly involved muscle, vessels, and nerves. Because of the unknown anatomic extent of tumors, he advised that cancers be excised widely with healthy tissue around them, but he regarded nasopharyngeal cancers and firm and livid tumors of the extremities inoperable due to local extent of invasion. He promoted thorough physical examination before surgery. During surgery, he used a sponge saturated with opium and mandragora juice for general anesthesia.8, 9, 15

French surgery was founded by Lanfranc (1252‐1315), a native of Milan who was driven out of Italy for political reasons. He practiced medicine and surgery in Paris and was an ardent opponent of the separation of medicine and surgery. He gave the first description of how to differentiate benign tumors of the breast from cancer. He advised surgeons to learn about the complex anatomic setting of vessels and nerves before they operate. Lanfranc summarized his thoughts about cancer in his 2 texts, Chirurgia Parva and Chirurgia Magna.5, 10 Henri de Mondeville (1260‐1320), a French physician, was the first to publicly reject Galen's nearly 1000‐year‐old theories. He simplified terminology by pointing out that scirrhus and carcinoma had the same meaning and both of them were cancer. He divided cancers into simple and compound forms on the basis of history of prior lesions. He also introduced the classification of cancers with consideration of size, anatomic site, and whether the tumors were superficial or deep in location. Mondeville advanced the concept of external carcinogens and assumed that the carcinogens entered the body through orifices of glands.9, 11, 16

Guy de Chauliac (1300‐1368), a French surgeon, devoted one chapter in his book, Chirurgia Magna, to skin diseases and cancers. He distinguished hot and cold lesions. The hot tumefactions were pustules, abscesses, and gangrenes, and the cold ones were cancers. He treated operable cancers with wide excision.17 Patients with inoperable growths were treated with nutritive diet and purgatives. Anorectal lesions were the primary interest of John Arderne (1307‐1390), who practiced in London and is remembered as the first proctologist. He noted that many anorectal benign lesions and cancers may present with identical symptoms but that most cancers could be felt with the tip of the finger as hard indurations or irregular polypoid masses. He regarded blood, mucus, and constriction as cardinal signs of cancer. Despite his extensive surgical experience with anorectal lesions, he recommended only local excision for cancers because, as he wrote in his De Arte Phisicale et de Chirurgia, he had never seen a person recover from cancer of the rectum.9, 18

The physicians and surgeons who cared for cancer patients during the 4000 years covered in this review were the pioneers in oncology. Despite their shortcomings, all contributed many ways to the detection, diagnosis, and treatment of cancer (Table 1).