The History of the Breast and Breast Cancer

The female breast has symbolized beauty, sacredness and femininity throughout history. Although belonging to women, babies named it, with words such as meme, mama . As a disease, breast cancer has interested and challenged physicians since antiquity. Surgery, the foundation of its treatment, inevitably left an unpleasant appearance, particularly in earlier times. Stories of attempts to treat breast cancer form a complex labyrinth, because this now largely treatable disease has many forms, understood only through enormous effort.

Because the breast is easily identifiable from its location, written records and examples of breast cancer even from ancient times are unsurprising.

What Is the Breast as an Organ in Both Women and Men?

The breast is actually a differentiated sweat gland. If this differentiation occurred only in women, it could be explained functionally, but men also have breast tissue. Breast cancer occurs in men too, although less frequently: approximately every 150 female breast cancers correspond to 1 male case. Differences between male and female breast tissue begin when sex differentiation occurs in the 11th week of pregnancy.

- Related topic: Breast cancer can occur in men too. Today, treatment success approaches that achieved in women

Ancient Beliefs and Practices

The earliest written cancer records, the Edwin Smith Papyrus , concerned breast cancer and dated to around 1.600 BC, approximately 5000 years ago. The papyrus contains original descriptions of breast cancer surgery. “The breast cannot be touched, is swollen, and cancer has spread throughout it” was considered an incurable condition. In ancient Greece, divine help was sought for breast disease, as shown by breast-shaped offerings to Asclepius, the Greek god of medicine and health, in temples. Ancient Egyptian scrolls from the 1600s BC describe 8 breast cancer cases treated by cauterization. In 400 BC, the Father of Medicine , the Greek philosopher Hippocrates, proposed that cancer resulted from imbalance of four bodily fluids: blood, phlegm, yellow bile and black bile. The idea that black bile caused cancer remained influential for over a thousand years.

Saint Leonidas of Alexandria, in the 1st century AD, described skilled, courageous surgical removal of breast tumors and cauterization in detail. Removing tumors through broad incisions laid foundations for today’s oncological surgical principles. In AD 200, Galen regarded breast cancer as a systemic disease involving accumulation of black bile in blood. These ancient physicians linked cessation of menstruation with cancer—an early idea of a relationship between cancer and older age. Accordingly, Galen allowed surgical wounds to bleed freely to release black bile and considered thread or wire suitable for tying an opened vessel.

Surgical Stagnation in the Middle Ages

Between AD 476 and 1.500, there was no significant medical progress. Under Christian beliefs of the time, rather than surgery considered barbaric, diseases were preferably healed through miracles and faith .The Islamic world’s revival of Greek medicine through meticulous translation preserved medical knowledge for future generations. In the 10th century, the Persian Islamic scholar Ibn Sina (known in the West as Avicenna ) and Albucasis (Abu al-Qasim al-Zahrawi, Spain), and in the 12th century Maimonides (Spain), were three renowned physicians who spread medical accomplishments to expand Islamic achievements. Abu al-Qasim strongly supported surgical cauterization. Using caustic paste to destroy tumors and make them operable recalls today’s rationale for chemotherapy in large breast cancers. Abu al-Qasim, Henri de Mondeville (the “father” of French surgery, 13th century) and Guy de Chauliac (France, 14th century) introduced unique instruments into the surgical armamentarium—the full range of medical techniques, equipment and supplies used by physicians or institutions for a task—to help rapidly remove breast tumors.

Renaissance: Celebrating Art and the Emergence of Surgery

The 16 – 18th centuries were a golden age not only of artistic creativity but also of surgery’s emergence. Moving beyond barbering, surgical skill advanced in 16th-century Belgium through Andreas Vesalius’s anatomical exploration of the human body In England and France in the 18th century, Cooper’s breast ligaments and Sappey’s subareolar lymphatic network took their place. John Hunter, a Scottish father of surgery, replaced “black bile” with lymph as the cause of breast cancer. Theories involving curdled milk, trauma, personality, air exposure and infection shaped the concept of carcinogenesis (cancer development) . Records describe many heroic operations, ranging from simple lumpectomy, removing only the tumor area, to radical removal of the whole breast with the pectoralis chest muscle. Without anesthesia, these procedures were impressive and admirable; skill and speed were essential surgical qualities. Surgery was the only hope of treatment then. Other recorded practices attempted breast removal through ligation with thread or wire or use of a lead plate.

The 19th Century: Surgery’s Golden Age

Advances in anesthesia and antisepsis made the 19th century surgery’s golden age. Many discoveries rapidly developed around basic principles, making surgery safer and improving outcomes. Disinfection, removing infectious agents; sterilization, eliminating all microbes; and sterile gloves were early turning points.

General anesthesia transformed surgery, making it easier for surgeons and certainly for patients.

Although James Blundell attempted blood transfusion for postpartum hemorrhage in 1818, safe blood transfusion succeeded in the early 20th century after Karl Landsteiner discovered blood groups. In the 17th century in England, Hooke, and in the 19th century in Germany, Müller and Virchow described normal cells and their cancerous relatives using the microscope , making major contributions to cancer understanding. Müller explained that cancer consists of living cells and proposed that metastasis results from their spread, ending humoral theories of cancer’s origin. Breast cancer spread through lymphatic vessels to underarm nodes became the basis of various excision techniques (axillary dissection).

In the mid-19th century, bold radical operations gained acceptance. Charles Moore in England and Kuster and Volkmann in Germany followed parallel paths. William Banks performed axillary lymph node dissection in Liverpool, England, in 1882. Though destructive by the standards of the time, it offered an opportunity to study disease spread. By century’s end, breast surgery became associated with Professor William S. Halstead at Johns Hopkins Hospital in Baltimore, United States. His approach removed tissues in one piece to prevent spread and the pectoralis major chest muscle to prevent recurrence, through radical mastectomy , first reported in 1894. It laid the foundations of modern breast cancer surgery and became the undisputed path followed diligently by subsequent surgeons.

A Turkish Physician Who Made Breast Cancer History: Dr. Cemil Topuzlu

The first breast cancer operations in our country were performed in the late 1890s, an early period, by the physician known as the founder of modern Turkish surgery, Dr. Cemil Topuzlu .

After graduating in 1886 from Mekteb-i Tıbbiye-i Şahane (the Imperial Military Medical School) in Gülhane, Dr. Cemil Topuzlu was sent to Paris in 1887 for surgical training. He worked as a resident at St. Louis Hospital for three years. Returning to Istanbul in 1890, he became head of surgery at Haydarpaşa Military Hospital. While clearing the axilla during breast cancer surgery, he injured an artery and sutured its divided ends together. The same occurred in another patient. He presented these cases and his technique at the Moscow Surgical Congress in 1897. In America, Alexis Carel published the same technique 5 years later in 1902… Dr. Topuzlu served for many years as a surgeon and Istanbul’s mayor, training many distinguished surgeons. In 1958, the year he died, Harbiye Open-Air Theater was named after him.

“Tissue suspected of cancer must be removed in one piece, preventing wound infection or cancer breaking apart and spreading to other tissues” and similarly strict rules of the time prevented preoperative biopsy. This view was later recognized as incorrect, and diagnostic preoperative breast biopsy became routine. Another abandoned practice was leaving surgical wounds open to granulate, or repair tissue. Ligatures, the thread or wire used in surgical suturing, now promote better wound healing and lower infection rates.

The First Targeted Cancer Treatment Was Developed for Breast Cancer: Tamoxifen

Discovering that some breast cancers are sensitive to the female hormone estrogen exemplifies efforts to understand breast cancer. Estrogenis secreted mainly by the ovaries and is important for maintaining and growing normal breast tissue.

In the 1920s, some women whose ovaries were removed for various reasons experienced breast cancer regression. This raised the question: “Does breast cancer obtain its fuel from ovarian estrogen?”

In the mid-1960s, young chemist Elwood Jensen approached the answer. Hormones, as he knew, functioned by binding a receptor in the target cell, but the estrogen-binding receptor had not been identified. In 1968, Jensen radioactively labeled estrogen and found the receptor, the molecule binding estrogen and transmitting its message into the cell.

Jensen was even more surprised when investigating whether breast cancer cells carried this receptor: some did and others did not. Breast cancer cells could therefore be divided into those with many receptors (hormone-positive or ER-positive) and those with few (hormone-negative or ER-negative).

This discovery launched the search for an antiestrogen drug suppressing estrogen function, but none had yet been discovered. Pharmaceutical companies focusing on menopause treatments and new birth control drugs using synthetic estrogens had already abandoned antiestrogen development. Cytotoxic drugs, now called conventional chemotherapy, were just emerging and were the favorites of cancer treatment. Hormone-based cancer treatments therefore attracted little interest.

Consequently, when Imperial Chemical Industries filed a patent for a chemical called tamoxifen in 1962, few noticed. Initially intended as a contraceptive, tamoxifen was developed by a team led by hormone biologist Arthur Walpole and synthetic chemist Dora Richardson. But instead of switching estrogen signaling on, as required for a contraceptive, it unexpectedly switched signaling off in many tissues. It was therefore an estrogen opponent, an antagonist. It might not work as contraception, but could estrogen-sensitive breast cancers be different?

To test this idea, Walpole and Richardson found a clinician collaborator: an oncologist and radiotherapist at Manchester’s Christie Hospital with a particular interest in breast cancer, Mary Cole. Known as dedicated, proactive, courageous and meticulous, she cared for women with advanced, disseminated breast cancer. She was prepared to try anything to save them—even a discarded contraceptive considered ineffective.

Cole’s trial began in 1969, treating 46 women with breast cancer using tamoxifen tablets. Expecting little beyond partial improvement, she was surprised when ten patients responded rapidly and clearly. Breast tumors shrank, lung metastases regressed, bone pain disappeared and lymph nodes softened.

In many responding patients, cancer reappeared after a while, but the trial’s success was clear and its proof of principle historic. This new hormone drug, capable of regressing even disseminated tumors, became the first drug designed specifically to target a particular process in a cancer cell .

Later, in 1973, biochemist V. Craig Jordan used a molecular staining technique to identify breast cancer cells carrying estrogen receptors. Cells with these receptors bound tamoxifen; the antiestrogen drug prevented estrogen from functioning in the cell, stopping growth and proliferation. ER-negative cells lacking drug-sensitive receptors did not respond.

For the first time in cancer history, a drug, its target and the cancer cell came together through a fundamental molecular rationale. Tamoxifen was therefore the first targeted drug developed for cancer treatment.

The Triumph of Biotechnology

Trastuzumab, a monoclonal antibody developed against the HER2 receptor, is among the first drugs associated with breast cancer treatment today. It was discovered by Dr. Axel Ullrich and Dr. H. Michael Shepard and later developed by Dr. Dennis Slamon. A book about Slamon’s life and breast cancer research was adapted into a film called Living Proof in 2008.

Genentech, the biotechnology company that also developed human insulin, developed trastuzumab with UCLA (University of California, Los Angeles). Its first clinical trial began in 1992 with 15 patients. By 1996, driven by treatment success, patient numbers exceeded 900.

In 1998, the drug with active ingredient trastuzumab and brand name Herceptin received, for a subtype of metastatic breast cancer, FDA approval , regarded then as a triumph of biotechnology.

Approximately %25-30 of breast cancer patients, because of a genetic change, have much higher than normal levels (overexpression) of HER2 (human epidermal growth factor receptor-2) on their cell surfaces. Overexpression of the HER2 protein involved in cell growth and proliferation is associated with more aggressive disease.

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The Maturation of Surgery and Adoption of a Multidisciplinary Team Approach to Breast Cancer Treatment

The legacy of Halstead, father of modern breast cancer surgery, “Great surgeons make great incisions, and therefore perform great operations” persisted for a time. But in the late 19th and early 20th centuries, this view slowly faded. Patey and Handley in London and Auchincloss Jr. in New York began modifying radical mastectomy to preserve the pectoralis major. New chemotherapy approaches and rapid radiotherapy advances also emerged to kill cancer cells. Medical castration (hormone suppression) and discovery of targeted mutated tumor receptors such as Her2 required reconsideration of cancer management strategies, together with growing knowledge of breast cancer biology. Mammography detecting smaller cancers added a new dimension to surgical management.

The call to return to limited surgery came from the surgical community. Professor Bernard Fisher, a surgeon at the University of Pittsburgh, revived Galen’s concept of breast cancer as a systemic disease. It is ironic that abandoning the radical Halstedian approach and research establishments and accepting neoadjuvant treatment, preoperative tumor-shrinking chemotherapy, was a surgeon’s brilliant idea!

Surgery reinvented itself to integrate with other methods.

As the 20th century ended, breast conservation and reconstruction, with sentinel lymph node dissection when needed, became effective. Removing and examining selected sentinel nodes, the first nodes receiving tumor spread, prevented unnecessary removal of all axillary nodes and substantially reduced postoperative lymphedema of the arm.

Surgeons led a revolution reducing major tissue loss. This opened doors to synthetic materials and innovative autologous tissue transfers offering shapes that could even surpass nature’s original creation. Muscle, myocutaneous flaps, lipomas and omentum, the membrane covering the intestines, became natural options. Holmstrom introduced the transverse rectus abdominis myocutaneous flap (TRAM) in 1979, and it evolved through many modifications. Prosthetic and synthetic options stirred industrial and commercial debate: petroleum jelly, ivory, rubber, polyvinyl alcohol sponge, silicone—the list goes on. Mature breast cancer surgery remains central to managing the various treatments for this disease.

Rather than completely destroying, surgery now comes to the aid of breast cancer patients, balancing appearance with treatment.

You can find all developments in breast cancer in our Breast Cancer News section.

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