The History of the Therapy for Breast Cancer

Documentation for the Existence of Primitive Cases of Breast Carcinoma: the Edwin Smith Papyrus and the Ebers and the London Medical Papyri

Archival history suggests that primitive breast cancer descriptions existed as early as 37 centuries ago (c. 3500 BCE), clearly illustrating knowledge of breast cancer among female patients. Hierarchal dating of the papyri suggests that these documents were created between the years 3500 and 2500 BCE (concurrent with the Stone Age). Deciphering the Egyptian hieroglyphics revealed ancient documentation and primitive medical text contained within the Ebers Papyrus , first purchased from the Egyptian antiquities dealer, Mustafa Agha, in 1822 in Luxor, Egypt. Most art antiquity scholars consider the research scholar, adventurer, entrepreneur, and philanthropist Edwin Smith (b. 1822) to be the principal historian who recognized the worth of this priceless papyrus. Smith was instrumental in ensuring protection of and care for the historical treasure, recognizing the value of preserving this record of the natural history of multiple diseases that afflicted this ancient Egyptian population. The 40-year-old American-born Smith, an antiquities dealer himself, while living in Luxor, purchased the papyrus from Agha in 1862, some 40 years after Agha acquired it. Smith, possessed this document for 44 years until it was bequeathed—with other antiquities from his estate—by his daughter, upon her father’s death in 1906.

Today, the Edwin Smith Papyrus is uniquely treasured as the principal and priceless artifact among the four extant medical papyri that exist today. In contrast to the Smith papyrus, the Ebers and London Medical papyri represent medical hieroglyphic textual documents founded in medicinal “magic.” Of notable distinction, the Edwin Smith Papyrus (c. 1600 BCE) is considered to be the sole extant antique text created to instruct ancient physicians in surgical technique, clinical therapy, scientific methodology, and the rationale for practice—some 37 centuries ago. This papyrus is considered to be the oldest known surgical text in the history of civilization. Further, the papyrus cast aside the unscientific “mysticism and prevailing magic” of the era to favor logistic thought and deductive reasoning. With the decline of the Egyptian civilization over the next millennium, the teachings and value of the papyrus were lost. Scholars suggest that ancient Greek physicians and scholars knew the intellectual value of the papyrus; however, physicians did not fully implement logistical reasoning and deductive thought until the Hippocratic era (c. fifth century BCE), while the Smith papyrus contained medical writings that were congruous with and relevant to those principles. Moreover, the Smith papyrus, purposely formulated for use in this primitive era, was revered as an instructional document for medical practice but remained a uniquely controlled tome under the aegis of renowned medical scholars of the ancient Egyptian scholarly clientele.

van Middendorf and colleagues completed a clinical reappraisal of the papyrus in 2010. Lawrence described, in 2008, the concise reappraisal of the papyrus, which is unequivocally considered to be the first known document describing trauma surgery. Additional trauma injuries with detailed presentations were predominantly illustrative in the artifact; included were six patients with injuries to the spine. Thus, as others have surmised, the Edwin Smith papyrus may have been a primitive manual intended to direct medical and surgical therapies for trauma incurred during ancient Egyptian military warfare. In stark contrast, the Ebers papyrus and the London Medical Papyrus were medical hieroglyphic texts specifically pertaining to medicinal “magic” and mysticism. The Ebers papyrus is a collection of hieroglyphic texts related to injuries of specific organs, with accompanying descriptions including: specific complaints, diagnosis, prognosis, and the proposed therapeutic option for the ailment. In distinction, the massive Edwin Smith papyrus is a scroll of 4.7 m (15.3 ft) length of which the front ( recto ) possessed 377 lines aligned in 17 columns; the backside ( verso ) included 92 lines arranged in five columns. This papyrus contains syndromic descriptions by ancient Egyptian physicians of 48 cases, for which modern diagnoses cannot be accurately formulated, as the descriptions are missing information with regard to patient symptoms and/or diagnosis. Many of the classic publications were philologically oriented.

The papyrus has had many homes since departing ownership by Smith, including the New York Historical Society and the Brooklyn Museum; however, today the papyrus is housed in the archives of the New York Academy of Medicine in New York City. The priceless papyrus was donated to the New York Historical Society in 1920 and entrusted to study, interpretation, and codification by the renowned Egyptologist James Henry Breasted (b. 1865). Breasted is credited with translating the hieroglyphics into the Egyptian language and then into English, which Smith was unable to achieve. Breasted translated the entire papyrus and published a historic two-volume edition in English, with a compendium of medical notes prepared by physician-physiologist Arno B. Luckhardt (b. 1885). The translations were completed by Luckhardt with guidance from Breasted in 1930, and the published text is accompanied by commentary and hieroglyphic transliteration.

Breasted and co-author Luckhardt translated the text describing a total of 48 patients with a panoply of diseases, including trauma, congenital abnormalities, neurological and orthopedic injuries, and multiorgan tumors. Eight of the cases described within the massive papyrus were breast tumors and/or breast ulcerations—the first-known clinical descriptions of breast cancer in any extant literary document. These initial descriptions of breast cancer were entitled: Instructions Concerning Tumors on the Breast ( Fig. 1.5 ). The physician examiner, as shown in Fig. 1.5 , specifically described a breast carcinoma as a bulging tumor, very cool to touch, to be an ailment for which there was no therapy. Nihilism was the rule when default of when exceptional therapy was unavailable.

Hieroglyphic authorities reasoned that the Smith papyrus contained certain sections addressing gynecology, tumors of various sites including the breast, and cosmetics; all were discussed in hieroglyphics on the document’s verso. Except for one small section of the papyrus, one scribe wrote the entire document. Breasted considered the most likely author of the document to be Imhotep (c. 2650 BCE), the renowned physician, architect, astrologer, and “priest of privilege” for the Old Kingdom (c. 3000–3500 BCE). Imhotep was an Egyptian chancellor in service to Pharaoh Djoser; Imhotep was also the Pharaoh’s architect, responsible for designing the step pyramid dedicated to the sun god Ra at Heliopolis.

Details regarding the management of traumatic orthopedic and neurological injuries were revealed in 1992 the hieroglyphics expert Robert Wilkins. Of note, the Smith papyrus includes the 16th and 17th Egyptian Dynasties of the Second Intermediate Period (c. 1600 BCE), when the ancient nation was ruled from Thebes. It is highly probable that Breasted and Luckhardt completed editing the papyrus translations in 1930. This tour de force was seminal to 20th to 21st century comprehension of initial advancements in scientific progress in this primitive Egyptian era.

Chinese Influence With Recognition of Breast Diseases

Xuanyuan Huangdi, “The Yellow Emperor” (b. 2717 BCE), was the third of ancient China’s mythological Emperors, and is also considered to be the patron saint of Daoism and a revered cultural hero. Huangdi began his rule in 2697 BCE. His patron element was earth, and he allegedly derived his knowledge of medical matters from goddesses and immortals. Considered to be god-like in Chinese folklore and religion, “The Yellow Emperor” was thought to be endowed with the five highest forms of deity. Huangdi was the principal author of the ancient text, Huangdi Neijing , which also came to be known as the Inner Canon of the Yellow Emperor . Considered the oldest treatise on medicine, the Canon departed from old shamanistic lore suggesting that demonic influences were central to presentation and principally responsible for all diseases. Rather, the Canon stated the natural effects of four factors were responsible for human disease: diet, lifestyle, emotion, the environment, and aging. The Canon provided Chinese scholars with the first descriptions of tumors and five therapeutic variants: spiritual care, pharmacology, diet, acupuncture, and variable options for a variety of diseases.

Ancient Magic of Babylonian Medicine

Markham Geller’s text, Ancient Babylonian Medicine: Theory and Practice (2010), provided insight into primitive medical practice in Babylonia, which had no semblance to any variant of contemporary allopathic medical therapy. Perhaps influenced by Greek medical scholars, Babylonian theorists considered that medical outcomes depended heavily upon “magic.” The illusion and trickery of “magic” played a central, primary role within ancient Babylonian medical practice. An exorcist collaborated with the physician in medical practice, utilizing supernatural spirits to formulate prognosis and treatment.

All variants of herbal therapies and natural organic therapies were administered together with a “spell” or an incantation in ancient Babylonian medicine. Thus medicines used in this culture could not be scientifically considered “therapy.” Rather, animal products (inclusive of feces and other organic matter), minerals, and plant life were considered the staple ingredients of their ancient medical apothecary. Thus the health care system of ancient Babylonian culture relied heavily upon deep incantation or prayer, perhaps even more so than the natural herbal therapeutics administered by Babylonian “physicians.” Such unfounded beliefs, saturated with supernaturalism, were similar to previous supernatural views held earlier by Egyptian physicians. The futile practices were common in the second half of the second millennium BCE, with Syrian copies of Babylonian text frequently read by practicing physicians of the era.

Babylon’s King Hammurabi commissioned medical scholars to create a separate papyrus during the Second Intermediate Period (mid-16th–17th centuries BCE). The newer document was contemporary with the revered Egyptian papyri. This new papyrus was referred to as the Hammurabi Code (c. 1756 BCE) and contained a list of 282 case laws written and sanctioned by King Hammurabi during his reign (1792–1750 BCE) as monarch of the first Dynasty of Babylon. The Code provided a code of conduct for medical practitioners that dealt with physician responsibilities and fees. Surgery was primitive and primarily comprised rudimentary procedures such as dental extractions and cutaneous lesions (for example, opening peripheral cutaneous abscesses of soft tissue and skin with a bronze lancet). Internal medicine was not evidence-based but consisted mainly of recitation of litanies and incantations against the demons of earth, air, and water.

However, the Babylonian Second Intermediate Period was a sinister era of punitive reprisals upon physicians, as loss of a patient’s limb or the death of a patient could incite amputation of the physicians’ hands and/or death. Clearly, suspicious and supernatural beliefs dominated every physician’s practice in primitive Mesopotamia. The use of astrology for prediction of prognosis and therapeutic intervention was described in the 11th century BCE text authored by Esagil-kin-apil, chief scholar of the Babylonian King Adad-apla-iddina (b. 1067) and entitled Sakikkū– Diagnostic Handbook . This medical treatise was a revered guide for identifying symptoms, ascertaining etiology (including supernatural causes), and providing a prognosis. This tome became the principal medical diagnostic text of the first millennium. Like the primitive Egyptian papyri, the Sakikkū– Diagnostic Handbook dealt with the supernatural. However, diseases were not always attributed to natural causes: rather, afflictions were thought to result from angering gods, spirits, or ghosts. These Babylonian scholars utilized astrology and other supernatural/suspicious methodologies to define prognosis and therapy. The author, Esagil-kin-apil, noted that physicians often worked together with an exorcist to provide patient care. This text stated that the type of animal noted by the physician when en route to see a patient would dictate the patient’s outcome. As an example, the physician sighting a white or an unblemished pig portended an excellent outcome. In contrast, encountering a black pig portended an extremely grave condition or certain death. This era of nonscientific, unproven therapies could hardly be called the “Babylonian era of medical practice”; rather, the deplorable techniques and therapies consistently led to poor outcomes for the unfortunate patient.

First Description of Breast Cancer (Sixth Century BCE)

Historians François Retief and Louise Cilliers referenced writings by Herodotus (b. 484 BCE), who in the sixth century BCE published his tome, The Histories , containing a detailed chronology of “inquiry” regarding the origins of the Greco-Persian Wars, as well as ancient Greek medicine and history. Herodotus documented that the Greek physician, Democedes, a captive of the Persian king Darius the Great, successfully managed to cure a phuma (unknown histology) that had been discovered in Atossa, the king’s wife. Apparently, Atossa’s breast tumor erupted and grew, suggesting this could have been an ulcerating carcinoma of the breast. Unfortunately, Herodotus did not describe Democedes’ technique, nor the instrumentation used in the successful surgical ablation.

Classic Greek Era (c.460–136 BCE)

Medicine in eastern and western Europe originated in ancient Greece in the fifth century BCE. Born on the Aegean sea isle of Kos, Greece, in the age of Pericles, Hippocrates (b. 460 BCE) is credited with incorporating ethical ideals into the concept of clinical advancement in Medicine. Hippocrates was considered the “Father of Medicine” and traveled widely throughout Greece and Asia Minor, teaching students and established physicians alike.

Ancient Greek medicine was formulated on the “theory of humors.” “Humor” referred to the four common bodily (corporeal) fluids: blood, phlegm, yellow bile, and black bile. To these ancient practitioners, illness was the product of an imperfect balance among these four humors. Such concepts would permeate the teachings and practice of every physician of the era; the theory of humors was credibly enunciated by Hippocrates after establishing a medical school at Kos. Following the school founded in Cnidus, Kos was the second school of medicine founded in Greece. These beliefs in the humors formed the basis of the Hippocratic Corpus and led to Hippocrates making ethical recommendations for medical practice, including penning the Hippocratic Oath for the practicing physician, which is still recited by graduating medical school students today. Greek medical scholars defined the characteristic intellectual/scientific differences between the first two medical schools in Greece: the faculty of Cnidus were interested in the “local” character of disease, whereas Hippocrates and his faculty emphasized the “general” character of disease, and supported the concept of “general medicine.” Cnidus physicians focused upon “ disease—rather than the patient ,” whereas Hippocrates and the Kos faculty had strongly “ emphasized the patient ” rather than the disease. Hippocratic physicians provided diagnoses and proper therapy based on the recognized functions of the human body and evaluation of each patient’s “physical findings.”

Hippocrates advanced his theories of philosophy, physiology, anatomy, and the conceptual basis for disease during the Golden Age of Pericles and stated (incorrectly) that the four corporeal (bodily) humoral fluids were etiologic to all human diseases. This dominant, but erroneous, medical teaching of the Periclean Age was formulated without medical-scientific rationale or evidence-based experimentation. Simply, the organic production of the various liquid components of the human corpus (blood, phlegm, yellow bile, and black bile) were “end-products” of organic events still observed centuries later in all humans: bone marrow and spleen synthesis (blood products); secretions of the larynx, pharynx, and lungs (phlegm); synthesis and secretion into the biliary tree and smaller canaliculi from the liver cells (hepatocytes—yellow bile); and lastly, gastric acid with oxidation of food-liquid substrate and biliary secretions (black bile), respectively. However, Hippocrates further deduced (correctly) that the four humors do not in any manner take on the formative matrix of nature to incorporate the four elements of the universe: air, fire, earth, and water. Biographer Jacques Jouaana emphasized that Hippocrates’ writings did not connect the four humors to the four elements of the universe. Likely the theory arose that health prevailed within “balance of the humors,” whereas various diseases occurred when “imbalance prevailed.” Hippocrates considered that breast cancer likely occurred from an “imbalance” of these four humors, as outlined in his treatise The Nature of Man . Moreover, the “Father of Medicine” considered that “women and men have four kinds of moistness in their bodies and from these fluids diseases originate, except for afflictions caused by force … these being…phlegm, blood, bile, and water.” However, Hippocrates incorrectly postulated that the etiology of breast cancer was “humoral excess of black bile” representing an imbalance in the system of humors derived from nature. Further, he strongly advised against surgical removal of breast cancer, as he considered the procedure highly problematic, especially as wound care posed a threat to life—a threat even greater than the “karkinoma” (carcinoma) itself. Additional descriptions by Hippocrates included phuma (an inclusive term that spans many tumor variants, nonmalignant or inflammatory in origin, including: small breast tumors [tubercula of lactation; fibrocystic disease; and retention cysts]). The Hippocratic writings also referred to other tumor varieties such as oidê·ma that were soft, nontender tumors that often “pit” or “dimple” with focal pressure, and may have been a descriptor of subcutaneous tissue swelling (edema due to excess fluid). In actuality, Hippocrates coined the word “karkinos” (carcinoma) when describing breast cancer in a woman from at Abdera, Greece to denote both non-ulcerous and ulcerous tumors of various organs. The eight descriptions of breast disease contained within the Edwin Smith Papyrus were demonstrative of what is now recognized as advanced locoregional carcinoma of the breast. Ancient Greek medical writings further elaborated on Hippocrates’ medical jargon to suggest that the erudite Greek physician recognized the form/shape of the neoplasm: lichen- or crust-like) surfaces that emulate a crab with pendulous arms that characteristically “pinch” with radial extension. He also described using heated irons and a “fire drill” for cauterization and hemorrhagic control during breast cancer removal, causing major morbidity and morality. Hippocrates erroneously divided all diseases into three general categories: those curable with medicine (most favorable); those not curable by medicine, but curable by the knife ; and those not curable by knife, but curable by fire . The Corpus Hippocraticum was a collection of 60 ancient Greek medical works dedicated to the treatment of various maladies: fractures, tumors, surgical procedures, asthma and chronic lung disease, allergies, and diseases of the skin. One case from the Corpus Hippocraticum describes a woman with breast cancer who presented with bloody nipple discharge. The association of the bloody nipple discharge with a palpable breast mass (carcinoma) lead Hippocrates to suggest that cessation of menstruation caused bloody engorgement within the breast, leading to growth of the carcinoma and the associated indurated nodules that exhibited local-regional extension into skin lymphatics with ulceration and/or extension to chest wall; what is essentially an inflammatory carcinoma (T4; T4 a–d). These two physical findings would become pathognomonic to current-day surgeons and the diagnosis of this neoplasm.

In this pagan pre-Christian and pre-Muslim era, the metropolitan complex of Alexandria on the Nile was founded in the fourth century BCE by Alexander the Great, in 332 BCE. Alexandria would remain the focal point of Greek science during the third and second centuries BCE. Greater than 14,000 students came to Alexandria to study Hellenistic knowledge. The ancient Egyptian city was the center of evolving medical scientific advancement that was contained in over 700,000 scrolls housed in the ancient libraries. These invaluable artifacts were destroyed by Julius Caesar’s (b. 100 BCE) forces during the siege of Alexandria, between 48 and 47 BCE, which was intended to destroy his son-in-law, Gnaeus Pompelius Magnus, Pompey the Great (b. 106 BCE). Rudimentary anatomic studies described in the manuscripts were conducted in Alexandria and were instrumental to the scientific advancement for the era, including the development of surgical instruments and techniques.

Hippocratic Physicians of Classical Greece (Fourth Century BCE)

With the Hippocratic doctrines of Greece’s classical era, which birthed medical scholarship and teaching, came the importance of physical diagnosis; however, there was little immediate progress in the scientific understanding of human disease. Physicians under Hippocrates’ mentorship used the term karkinos (skin carcinoma) to refer to any protrusion, frank ulceration, or palpable mass that originated (carcinogenesis) from “imbalances” of nature and portended a poor prognosis and clinical outcome.

In this fourth century BCE medical world, responsible surgeons often stated that no treatment was recommended for the patient; only rarely was excision recommended with cauterization with fire drills (for cauterization and bleeding control) and on occasion utilized to ablate the cutaneous or subcutaneous neoplasm. All the aforementioned presentations were pathognomonic for cancer diagnosis according to the cuneiform tablet medical text from Assyria, which was used as a reference by later Indian authors who described “bulging” of breast tissue, which could have been an unknowing reference to benign disease and/or abscess.

The Greco-Roman Classical Greek Era (150 BCE–CE 500)

Ancient Rome refers to the foundation of the city of Rome in the eighth century BCE. Within the next seven centuries, the Roman Empire (27 BCE–CE 476) became the dominant and most influential civilization in the world, but was technically considered an Empire upon decree by Augustus Caesar (b. 63 BCE), who declared himself Rome’s First Emperor in 31 BCE. Fifteen centuries would elapse before the Roman Empire fell with the 55-day siege of the dwindling eastern Roman (Byzantine Empire) city of Constantinople, in CE 1453, conquered by Sultan Mehmed II of the Ottoman Empire.

In the Pagan Era and with the fall and destruction of Corinth in 146 BCE, Greek medicine was forced to migrate to Rome. The Roman Empire was principally focused on military development and support, which resulted in profound loss of substantive advancement within medical sciences, occurring at the same time as rampant disease, and famine, plagues, food shortages, and inflation. In this primitive Roman culture, Italians and their conquered peoples depended upon medical herbs; assorted unscientific concoctions of dung, poultices, and plants; votive objects; religious rites within their churches; and superstitious objects as the principal determinants of health outcomes. Fig. 1.6 shows the statue of Diana of Ephesus. Diana was a fertility deity invoked by Roman women, and her display of feminine attributes includes 20 accessory pectoral breasts.

Of historical note only, the Greek physician Cato of Cos, Greece (b.234 BCE) advocated (erroneously) that cabbage poultice represented a universal panacea for all neoplasms. Cato suggested that the cabbage poultice extract had special value in the treatment of breast cancer. In the centuries following Hippocrates teachings, animal concoctions and vegetable and mineral oil products, besides cabbage, were considered antitumor therapeutics. Acceptance and recognition of surgery and cautery as therapeutics were quite delayed.

Aulus Cornelius Celsus (b. 25 BCE), a first-century Roman citizen of the classical Greek era, was an astute, erudite ancient physician known for his extant encyclopedic tome, De Medicina (c. CE 30), which contains an eight-volume compendium and two books regarding surgery (volumes—VII + VIII). Medical historians recognize De Medicina as the most significant contribution that followed Hippocrates’ original medical writings. With the influence of Pope Nicholas V, in 1443, Cornelius Celsus’ book became recognized as the first medical and surgical book to be printed (CE 1478) following the introduction of the printing press by Gutenberg Thereafter, Celsus described the “cardinal signs” of inflammation: calor (heat), rubor (redness), dolor (pain), and turgor (firmness, tightness). The latter descriptor, turgor, is also reflected in early descriptions of palpable cancer; as with Hippocrates’ earlier observations, turgor also suggested features of subcutaneous breast cancer and skin lesions of breast cancer, which had a harder armor-like density and shell-like appearance said to mimic that of “a crab.” The later writings of Hippocrates contain a pathognomonic description of scirrhous ( Gr . hard, hardened) carcinoma, the classic clinical finding for this common female neoplasm.

However, no additional cases of breast cancer or therapeutic advancements were recorded in the four centuries following Hippocrates’ initial observations of the disease, until the end of the Hellenistic Period (c.323 BCE–30 BCE) and conquest of Ptolemaic Egypt, the following year. Celsus described breasts as an anatomical site where cancer often presents in women; he also described the fixed-scirrhous irregular matrix of dilated tortuous veins, sometimes associated with ulcerations due to advanced local-regional disease. The observant descriptions by Celsus of early inflammatory breast cancer allowed primitive staging for the four clinical stages of cancer: (1) early cancer, cacoethes ; (2) cancer without ulcer; (3) ulcerated cancer; and (4)ulcerated cancer with cauliflower-like excrescence that bled easily. Celsus strongly advised against treatment of the last three stages by any method of surgical extirpation. In Celsus’ view, aggressive instrumentation of a cancer “irritated the neoplastic state” and initiated invariable recurrence with local-regional metastasis. Surgical resection of breast cancer, as described by Celsus and later by Leonidas, was typically carried out via “fire drill” cautery in antiquity ( Figs. 1.7 and 1.8 ).

First and Second Century CE

Aelius Galenus (Claudius Galenus, anglicized as Galen) (b. 129) was born in Pergamon, Turkey, on the Mediterranean coast near a shrine to the mythical healing Roman god Asclepius. In his 30 s, the erudite physician-physiologist emigrated to Greece, where he became an influential, internationally known medical scholar and philosopher who would influence European medical theory and practice for the next 400 years. His fame and respect were extensive. He became physician to Emperor Marcus Aurelius and would later serve as physician to Aurelius’ successors, Commodus and Septimius Severus. Even though medical therapies flourished during this time, surgery was usually avoided, in keeping with the premises formulated one-half millennium earlier by Hippocrates. Galen and Hippocrates held similar views of cancer management, although Galen recommended treatment, when curable.

Galen compiled significant Greek and Roman medical hypotheses from preexisting eras related to his own discoveries and theories. Best remembered as the originator of the experimental method and design for advancing medical investigation, his work was precocious and seminal, as he began lifetime dissections of animals in his scholarly quest to understand bodily function. As an example of his intuitive reasoning and experimental discoveries, Galen is credited with proving that urine is formed in the kidney, and not in the bladder, which was the common Greco-Roman teaching. Moreover, his most important discovery was that arteries transport the precious Hippocratic humor (blood) that sustains life. Four centuries would pass before, in 1543, the 16th century Flemish physician and anatomist Andreas Vesalius would observe that Galen’s brilliant human anatomical drawings were closely akin (if not identical) to anatomical features of animals (see later anatomical observations of Vesalius). Many of Galen’s sketches were derived from animal dissections. Some consider Galen’s most important contribution to be the recognition that circulatory transport of oxygen was via blood, not air. Prior teachings by physiologists had been incorrect for four centuries. However, Galen is not credited with the discovery of bodily circulation and its relation to heart function; this was discovered through animal experimentation by William Harvey (b. 1578) and is reported in his seminal 1628 publication, Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus (An Anatomical Exercise on the Motion of the Heart and Blood in Living Beings ). However, pulmonary circulation was first accurately described by Renaldus Columbus, Andrea Cesalpino, and Vesalius before Harvey’s contribution. Galen’s theories, developed over four centuries earlier, were confirmed with Harvey’s documentation of the dichotomy between the arterial and venous systems. Galen’s initial theories of blood transport between ventricles via invisible pores were incorrect, as he postulated that venous circulatory transport of blood occurred via a separate circulatory route reentering systemic circulation. Many of Galen’s experimental physiologic principles were seriously flawed perceptions of organ function; these misconceptions were founded in religious and social taboos that existed in an era that strictly prohibited dissection and study of human corpses—a major disadvantage for experimental science. He theorized that the human body consisted of three systems: brain and nerves, responsible for sensation and thought; heart and arteries, responsible for transporting life-sustaining energy; and the veins and liver, responsible for growth and nutrition (metabolism and organ secretion).

Galen was the original advocate of mastectomy, but recognized the futility of operating for advanced locoregional and metastatic disease; therefore he strongly concurred with Hippocrates’ commentary of four centuries earlier, to only proceed when the early-stage neoplasm could be completely resected. In this medically naïve era in which hemostasis was largely unknown, the possibility of major surgical wound complications precluded many operations, as uncontrollable hemorrhagic events were common in this primitive surgical era. In the absence of superior therapeutic measures, Galen strongly supported the Hippocratic concept of “excessive black bile” as the principal humor of disease that contributes to cancer of the breast. He never vacillated from the Hippocratic principle to “first, do no harm,” with interventions for advanced breast lesion deeply steeped in consideration of the complications. Galen’s principal deterrent for extensive surgery (full mastectomy) was the major complication of excess bleeding, accompanied by undefined, inevitable hemorrhagic shock. Further, Galen, while advocating an extensive list of herbal medications, supported the Hippocratic tenet to avoid any attempted operation for the deeply fixed posterior chest wall invasion. He also stressed the Hippocratic tenet that “hard breast lesions,” which he referred to as karkinoi genomenoi , would transform into (invasive) breast cancer. Thereafter, Rufus of Ephesus (c. first century) and Cassius Felix (c. second century) expressed similar views, attributed to Galen and Hippocrates, proffering conviction that breast cancer could not be cured, except in the early non-metastatic stage.

Four centuries subsequent to Galen’s original contributions, Byzantine Greek physicians and writers. Oribasius (c. first century CE) was discussed by Aëtius of Amida (b. 502), who wrote authoritatively on breast cancer and the sixth century based upon the medical views of the “divine” medical icon of the era: the ancient Greco-Syrian physician-surgeon Archigenes of Apamea (c. late first century). Archigenes became an advocate for application of complex specialized poultices for ulcerated breast tumors. Archigenes was quoted with criticism by Galen due to their differing hypotheses on differentiation of mental and organic illness. Galen would discredit Archigenes’ treatment of mental disease when treatment of psychological disease of the head should focus upon neurocentric organic disease but did not add pathognomonic distinction between mental and nonmental states. The prolific sixth century CE surgical scholar, Aëtius, differentiated ulcerated from nonulcerated variants of breast cancer, a distinction that would later be a surrogate for the “grave sign” (advanced locoregional disease) for the neoplasm that was firmly established by the 20th century Columbia University surgeon, Cushman Haagensen (b. 1900). Finally, Aëtius was among the first physicians to recognize the excellent prognosis for breast cancer confined to the nipple (Paget’s disease; in situ/invasive neoplasm). He considered this in situ/early invasive tumor to be curable in its early-localized phases of growth.

Galenic Influence Upon Leonidas

The Alexandria native and Greek physician Leonidas (b. second century) first belonged to the idiosyncratic sect of the Episynthetici, founded in the first century CE by Agathinus, with its nonscientific beliefs lacking medical grounding; many maintained that the sect was based on conjectural, nonscientific theory. The Greek physician Leonidas is not to be confused with Leonidas I, a King of the Greek city-state of Sparta in the fifth century CE. As a learned physician, Leonidas is credited with being the first surgical therapist for breast cancer. A pupil of Galen, Leonidas was highly influenced by the icon’s considerations for the management of breast disease; little remains of his surgical writings, except fragments preserved by Aëtius and subsequently by seventh century Byzantine physician/author, Paul of Aegina (b. 625). Leonidas described characteristics of breast carcinoma, including nipple retraction, and allegedly described mastectomy as a clinical treatment for advanced-stage breast neoplasms. It is evident that surgical instruments had been utilized by Greek physicians, at least as early as the voluminous, destructive eruptions of Mount Vesuvius in CE 79 (see Figs. 1.7 and 1.8 ). Well-preserved surgical instruments were discovered two centuries later from evacuations of Pompeii and Herculaneum that existed well before surgical extirpation of an organ was even considered by Leonidas; Vesuvius erupted approximately 150 years prior to these seminal organ-resections championed by the Greek surgeon. This third century Greek physician’s surgical resection principles, first extrapolated from Galen’s teachings, suggested that Leonidas utilized incision(s) into uninvolved remote skin, distantly removed from the breast neoplasm. With tumor recurrence that necessitated repeated incisions, Leonidas applied heat cautery to control hemorrhage, following extensive removal of all breast skin and tissues. Galen’s teachings regarding the “four humors” of harmful health events evidenced by “black bile” prompted Leonidas to attempt this aggressive surgical procedure to achieve curative resections. Success was achieved when the tumor on the surface of the breast, with its tortuous dilated venous “roots,” could be fully extirpated following colonic purging and bleeding of the tumorous site(s). These primitive procedures involved the surgeon allowing blood to “flow freely” with provision for “black bile” (admixed with blood) to drain from the breast incisions.

Prominent Christian Influences of 3rd to 16th century toEncourage Restoration of Medical Scholarship

The Christian era saw monks and clerics constituting the educated class and become medical providers in the Middle Ages. The year CE 529 witnessed the founding of the Benedictine Order by St. Benedict of Nursia; this was the monastery first established at Monte Cassino. Located in central Italy, in the mountains of Lazio, this is were where monks and clergy had a heightened interest in medical education within scattered cloisters of the Roman church. It was at Monte Cassino, following copying of multiple ancient manuscripts by monks, that the teaching and practice of medicine were vigorously reinstituted. Satellite monasteries developed throughout Christendom; selectively monastic schools opened in Italy, England, Scotland, Ireland, France, and Switzerland, after the eighth century. However, the greatest monastic saturation occurred on the European continent. Numerous religious martyrs of the first to sixth centuries were granted sainthood in recognition of their ethics, civil liberties, and righteousness. The Patron Saint of Breast Diseases (as well as nurses and victims of rape and murder, fire, natural disasters, etc.) was Agatha of Sicily (b. 231) ( Fig. 1.9 ). This third-century virgin martyr of the early church was horribly abused: both of Sister Agatha’s breasts were torn off with iron shears when she resisted Gov. Quinctianus’ vicious, deplorable, amorous advances. On Saint Agnes Day (February 5) two loaves of bread are ceremoniously escorted on a procession tray to depict the despicable act of physical mutilation that Saint Agatha suffered due to Quinctianus’ tragic command. The martyred virgin is one of many commemorated by name in the Canon of the Mass.

Paul of Aegina (b. 625), a seventh century Byzantine Greek physician, became a renowned surgeon after publishing his composition, Epitomae medicae libri septem , an unabridged seven-book medical compendium. This tome had a considerable influence on Islamic medicine. In addition, Paul of Aegina wrote two other monumental works on gynecology and toxicology. All of the tomes were based upon unabridged, nonoriginal contributions, which originated from Oribasius’ 70-volume Medical Encyclopedia . It was through these original Orbasius volumes that Paul of Aegina acquired and authored these Galenic-paraphrased medical volumes. Paul’s works contained considerable discussion of amputation of the breast, as well as detailed descriptions of trephining (for intracerebral injury), tonsillectomy, paracentesis, and mastectomy.

The Council of Rheims (11th and 12th centuries) excluded monks and clergy from practicing medicine; the task was assumed principally by lay practitioners. Just as important as the rise of university education in this time period, was the parallel rise in cathedral school practices. Responsibility for cathedral schools was soon placed within clerical hands, and the schools profited from greater freedom than previously was evidenced in monasteries. Moreover, the rapid rise in university educational freedom allowed unparalleled growth of all ethnic populations after the Bubonic Plague (or Black Death), which was caused by Yersinia pestis (originating in Mongolia and transmitted by fleas) and occurred in the mid-14th century (1347–1352). The plague impoverished Europe and Asia with mortality rates exceeding 50%. Soon after, Europe realized the paramount importance of educational freedom, and its quintessential nature to the maintenance of intellectual stimulation among its citizenry. This impetus and desire for educational improvement crescendoed in the 11th through 14th centuries; intellectual pursuit led to major realization of the necessity for enhancement of free university medical teaching centers, fully removed from the medieval medical education directives that were still dominated by monastic orders.

In 13th century Italy, an exiled expatriate of Milan, Lanfranc of Milan (Guido Lanfranchi) (b. 1250), an Italian surgeon who was educated by the famous William of Saliceto (b. 1210), contributed to medical teaching in Salerno during the Renaissance. Lanfranc became the personal physician to Philip IV of France and gained renown in Paris and internationally for his writings, Chirurgia magna and possibly, Chirurgia parva (short treatise) , extensive volumes that were published c. 1363 CE. These tomes were multidisciplinary compositions that included anatomy, embryology, ulcers, fistulae, fractures, phlebotomy, and scarification, together with diseases of various organs. The most important contribution by Lanfranchi was his chapter of The Chirurgia on brain injury, which appropriately described the symptoms and signs of concussion. He was an advocate of trephination, which was first practiced by 12th century Arab surgeons. He wrote sections on the medieval development of herbal pharmacology to enable manufacture of untested concoctions— inappropriately labeled as “therapies”––for cancer of the breast. It was the Lanfranchi who recommended separating surgeons from barbers as professions, writing brilliantly regarding the role and practice of the surgeon of their day and advocating that surgeons must have specialized, exceptional technical skills distinct from those of many medical physicians of the era.

Prominent Jewish Influences (Middle Ages)

Of interest, the principal Jewish influences within the Middle Ages era were of Spanish and Italian origin. Jewish physicians were active in Salerno, Italy, as early as the ninth century. Moreover, popes, kings, and nobles sought their medical services. Those of wealth and influence who were at risk of suffering poisoning at the hands of enemies were particularly interested in Jewish physicians’ provision of safe medical advice and medications. Egyptian caliphs and Arab rulers consistently preferred Jewish doctors to Mohammedan physicians who did not practice conventional medicine, but rather had a preference for magic and astrological therapy.

The Spanish-born philosopher, physician, Torah scholar and theologian Moses Maimonides (Moses ben Maimon—also referred to as Rambam) (b. 1135) was schooled in Cairo. In 1190, Maimonides wrote the philosophic masterpiece The Guide of the Perplexed , and even today is considered the greatest Jewish philosopher of the medieval Middle Ages. Maimonides was a Spanish physician and Judean theological scholar, philosopher, and influential Torah scholar of the Middle Ages. The esteem of his peers allowed him to be appointed to the Regent Court of Egypt for Sultan Saladin (the Great), establishing his leadership as a physician who developed medical treatises on a variety of diseases and presumptive cures of the era. Maimonides was considered to have influenced five generations of philosophers and scientists including Aquinas, Spinoza, Leibniz, and Newton. Maimonides’ Mishnah Torah , a masterpiece 14-volume compendium of Jewish law entitled, the Guide for the Perplexed , provide an extant view of Jewish thought and Orthodox practice. Maimonides became the leading rabbinic authority and scholar of his day, quite possibly of all times, aside from Jesus Christ. Maimonides was appointed court physician to the Regent of Egypt while Sultan Saladin (the Great) (b. 1138), Sultan of Egypt ,led military campaigns over 3 months against the Crusader states of the Levant, famously conquering The Latin Kingdom of Jerusalem in 1187, ending the crusade of Christendom into the Holy Land. Maimonides believed that Jewish law implied two principles: improvement of the body and improvement of the soul. The renowned philosopher of his day, Maimonides was a profound believer that the soul is improved by acquiring knowledge, and that the more knowledge one acquires, the greater the probability that the human can fulfill the commandments and love of God (Deuteronomy 6:5). Saladin conquered Jerusalem, in 1187, from the Franks—and his troops continually occupied it for 88 years, as protectors of the Holy City. Maimonides translated (from Arabic to Hebrew) the five volumes published by Avicenna (author, al-Qanum fil-Tib ) in the Middle Ages. Maimonides collected important descriptive aphorisms of Hippocrates and Galen.

Jewish physicians were prominent in Spain under the Western Caliphate, with academic advancement and teachings, until they were culturally banished in the same year (1492) as the founding of America. Salerno exploited Jews in the medical profession for their teaching prowess. Ultimately, Jews were excluded at Montpellier in the early 14th century, and it was only during the modern industrialized age that they were reinstated as citizens in Europe, at which point the welcome university freedoms allowed members of the faith to expand their brilliant medical talents internationally.

Prominent Arabic Influences (9th–12th century)

Western medicine is indeed indebted to Islamic physicians and scholars who were responsible for the preservation of the teachings of their Greek and Roman predecessors in their voluminous teachings and publications. Without the intervention of Arab scholarship, the writings of Greek and Roman physicians may have been lost to the ages.

Baghdad, then capital of the Islamic Empire and located within Iraq, became the epicenter for translation of Greek publications. The library at Cordova had at one interval over 600,000 manuscripts; this collection was housed in the Library of Cairo, which had 18 rooms dedicated to scholarly Arabic publications. The Turkish-speaking Tartars were a collection of variable ethnic cultures and the earliest Turkic-Mongolic-speaking persons of the region; Tartars originated in West-central Russia, east of the Ural Mountains. This vast geographic area was dominated by Mongol nomadic empires; these nomadic kingdoms were a warring faction. The Tartars destroyed the valued Library of Baghdad in 1260, throwing the priceless medical volumes into the waters of the Euphrates and the Tigris.

Rhazes (al-Razzi) (b. 865), one of the Arab kingdom’s greatest physicians, was among the first physicians of Islamic culture to condone excision of breast cancer, but only if the neoplasm could be completely extirpated and the residual tissue cauterized. Rhazes further warned surgeons of the day that incision, rather than excision, would produce residual ulcerations (recurrence).

Haly ben Abbas ( Ali ibn al-Abbas al-Majusi or Majusi) was a 10th century Persian physician, author, and psychologist of the Islamic Golden age. Majusi advocated removal of breast cancers with allowance for bleeding to evacuate “melancholic humors” that were widely believed to predispose women to breast cancer. There was no reference to cautery or bleeding control, and he did not suture (tie) arterial or venous vasculature.

Aviencca (Ibn Sina) was Haly ben Abbas’ successor and chief physician of the hospital at Baghdad. He authored the philosophical encyclopedia Kitab-Ash-shifa and the al-Qanum fil-Tib , which was later translated into Hebrew.