Breast cancer is one of the oldest recorded human diseases, but no single person can be credited with its “discovery.” The understanding of this disease has evolved across millennia, shifting from early physical descriptions and philosophical theories to aggressive surgical removal and finally to sophisticated molecular science. This long history is characterized by a gradual progression from recognizing the physical manifestation of tumors to comprehending the disease’s underlying systemic and genetic mechanisms. This evolution of knowledge has transformed a universally fatal condition into one that is often manageable and curable.
Ancient Awareness and Initial Descriptions
The earliest known documentation of breast tumors dates back to ancient Egypt, approximately 1600 BCE, recorded in the Edwin Smith Papyrus. This medical text describes bulging, untreatable masses in the breast, leading the ancient physician to conclude, “There is no treatment.”
The Greek physician Hippocrates, in the 5th century BC, provided the disease with its enduring name, karkinos, or “crab,” describing the tumor’s hard, fixed nature. Hippocrates and his successors, including the Roman physician Galen in the 2nd century CE, theorized that cancer was a systemic illness caused by an excess of “black bile,” one of the four bodily humors. This humoral theory dominated Western medicine for over a thousand years, suggesting that a localized tumor was merely a symptom of a body-wide imbalance and discouraging surgical intervention.
The Development of Modern Surgical Treatment
Despite the humoral theory, some early practitioners attempted physical removal of tumors. Aulus Cornelius Celsus, a Roman encyclopedist in the 1st century AD, described surgical excision for early-stage breast lesions, though he noted that operating on advanced cases often worsened the patient’s condition. The Renaissance anatomical revolution later provided the groundwork for safer surgery. Andreas Vesalius’s detailed anatomical text, De Humani Corporis Fabrica (1543), corrected long-held misconceptions by illustrating the human body based on direct dissection, offering surgeons a clearer map of the breast and surrounding structures.
The true shift toward aggressive surgical cure came with the work of American surgeon William Halsted in the late 19th century. Halsted developed the radical mastectomy, which he first performed in the 1880s and published in 1894. This procedure was based on the “en bloc” theory that cancer spread in an orderly, local fashion from the breast to the nearby lymph nodes and chest wall muscles. The radical mastectomy involved removing the entire breast, the underlying pectoralis major and minor muscles, and all of the axillary lymph nodes.
This extensive, highly disfiguring surgery became the worldwide standard for breast cancer treatment for nearly 80 years. Halsted’s technique achieved success in reducing local recurrence rates, dropping them from previous estimates of over 50% to approximately 6% in his initial series. The radical mastectomy’s dominance cemented the idea that breast cancer was a local problem requiring maximum physical excision. However, its morbidity, including severe lymphedema and shoulder dysfunction, eventually motivated the search for less aggressive approaches.
Pioneers of Systemic and Hormonal Therapies
A conceptual change began with the realization that breast cancer was often systemic, with microscopic spread occurring early on. The first hint of a non-surgical, systemic approach came from Scottish surgeon George Beatson, who in 1896 reported tumor regression in advanced cases after performing an oophorectomy (surgical removal of the ovaries). Beatson hypothesized that ovarian secretions fueled tumor growth, establishing the first link between hormones and breast cancer and challenging the surgical-only paradigm.
The systemic nature of the disease was further addressed in the 1970s with the advent of adjuvant chemotherapy—treatment given after surgery to destroy undetectable micro-metastases. Pioneering trials, such as those led by Gianni Bonadonna in Milan, demonstrated that drug combinations like cyclophosphamide, methotrexate, and fluorouracil (CMF) could significantly reduce recurrence risk. This proof of systemic benefit validated less aggressive surgery, leading to the adoption of the modified radical mastectomy and breast-conserving procedures.
The hormonal connection identified by Beatson was exploited with the development of targeted drugs like Tamoxifen, first synthesized in 1962. By the late 1970s, Tamoxifen was recognized as an effective endocrine therapy for tumors that express the estrogen receptor (ER). Tamoxifen acts as a selective estrogen receptor modulator (SERM), binding to the ER on cancer cells and blocking estrogen’s growth-stimulating effect. This discovery provided a non-cytotoxic, targeted treatment that significantly improved survival, ushering in the modern era of medical oncology.
The Molecular Era and Genetic Discoveries
The final transformation of breast cancer understanding came with the exploration of its molecular and genetic roots, explaining why treatments worked for some patients but not others. Geneticist Mary-Claire King provided a breakthrough in 1990 by identifying the location of the BRCA1 gene on chromosome 17q21, proving that a single inherited gene mutation could confer a high lifetime risk of developing breast and ovarian cancer. The subsequent discovery of the BRCA2 gene in 1994 confirmed the hereditary nature of a significant portion of breast cancer cases.
This new genetic knowledge provided the basis for risk assessment, preventative strategies, and the development of targeted drugs like PARP inhibitors, which exploit the DNA repair deficiency caused by BRCA mutations. Simultaneously, the identification of the Human Epidermal growth factor Receptor 2 (HER2) oncogene in the 1980s linked the overexpression of this protein to an aggressive form of breast cancer. The development of Trastuzumab (Herceptin), a monoclonal antibody that specifically targets and blocks the HER2 receptor, improved the prognosis for HER2-positive patients.
The ability to test tumors for estrogen receptor, progesterone receptor, and HER2 status now allows physicians to classify breast cancer into distinct molecular subtypes, such as hormone receptor-positive, HER2-positive, and triple-negative. This detailed molecular profiling forms the foundation of modern personalized medicine, where treatment decisions are tailored by the tumor’s unique genetic and protein fingerprint, not just its size or stage. This shift represents the culmination of the effort to move from merely describing the disease to understanding and targeting its precise biological mechanism.