Breast cancer is one of the most prevalent and deadliest malignancies. Undoubtedly, this disease has afflicted us since the beginning of mankind. The history of the fight against breast cancer is a history of human struggle with pain. In recent decades, there have been tremendous developments in the treatment of breast cancer and significant improvements in survival. Two hundred million years ago, at the end of the Triassic, the evolution of emulsion-producing skin glands occurred in a group of primitive dinosaurs that laid eggs called proto-cynodonts. These early mammary glands did not secrete sweat or odor, but instead produced a simple emulsion that served as a food supplement for the hatchlings. Over time, such glands coalesced together under the nipples and began to respond to sex hormones, such as estrogen. Breast cancer was first recorded in ancient Egyptian medical texts around 2500 B.C., describing 48 surgical phenomena, including a “swollen tumor on the breast. It is not known who the author was, but he described breast cancer as “a lump on the breast, large and hard, which can be broadcast and feels like a ball wrapped in bandages”. At the time, no interventions other than diagnosis could be offered. “There was nothing to be done”, the authors wrote. Around 2200 B.C., in the Qubbet el-Hawa, a large Egyptian cemetery near Aswan excavated in 2015, Egyptologists and anthropologists from the University of Jaén in Spain found a surprising object in the coffin: the skeleton of a woman. The skeleton had variants of metastatic breast cancer (as shown in the picture). The woman died 4,200 years ago and is the earliest known case of death from breast cancer. Around the year 1000, physicians began to explore the possibilities and limitations of performing surgery on breast cancer. In the eleventh century in Moorish Spain, the noted surgeon Abu al-Qasim al-Zahrawi wrote that breast cancer could be cured when “complete removal of the tumor became possible, especially in the early stages of the disease and when the tumor was small. “But when the breast cancer has been there for a long time and the tumor is large, you should leave it alone. I have never cured such patients, nor have I seen any other person successfully cured before me.” In 1590, French surgeon Barthélémy Cabrol suggested that advanced breast cancer should be cured by removing the breast gland as well as the chest muscles underneath. Others continued to try variations on this idea for centuries, but usually with dismal results. In 1896, Emil Grubbe of Hahnemann Medical College in Chicago, an electronics enthusiast, installed the world’s first X-ray device. x-rays burned Grubbe’s hands, and a colleague suggested that such x-rays could be applied to unhealthy tissue. The first recorded application of radiation oncology occurred in the same year that Grubbe’s machine was used to irradiate a woman with breast cancer named Rose Lee. In 1956, Robert Egan began the development of effective mammography, using X-rays to detect breast tumors that were not yet perceptible in size. By the 1970s, mammography became a common screening test for women. In 1975, the National Adjuvant Breast and Bowel Surgery Program showed that surgery combined with chemotherapy provided a better fight against breast cancer compared to surgery alone. Combination therapy became the standard of care for breast cancer. In 1977, the estrogen-blocking drug tamoxifen (pictured) was approved in the United States for the treatment of advanced metastatic breast cancer. Today, tamoxifen is one of many hormone-blocking drugs used worldwide to treat and prevent (in some cases) specific types of breast cancer. In 1990, Mary-Claire King and colleagues (J. M. Hall et al. Science 250, 1684C1689; 1990) used DNA samples from families with a family history of breast cancer to establish the relationship between mutations in a tumor suppressor gene and increased risk of breast and ovarian cancer. This gene, which she called BRCA1, was found to change the understanding of the effect of genes on cancer. Further studies showed that another gene mutation, BRCA2, could also increase cancer risk. Today, some women who test positive for these gene mutations, including actress Angelina Jolie (pictured), choose to have their mammary glands removed to reduce their cancer risk. In 1995, the American Nurses’ Health Study revealed that hormone replacement therapy (HRT) increased the risk of breast cancer. At that time, HRT was very commonly used by postmenopausal women for the treatment and prevention of menopausal symptoms. Today, HRT is no longer routinely recommended for long-term use in postmenopausal women. In 2000, Charles Perou and colleagues (C. M. Perou et al. Nature 406, 747C752; 2000) reported that breast cancer could be classified into several clinical subtypes based on different DNA mutations. Tumor cell DNA analysis allows physicians to select the most likely effective treatment. The “triple receptor-negative” subtype of breast cancer is particularly difficult to treat because these cancers do not respond to any of the breast growth hormone signals (estrogen, progesterone and human epidermal growth factor 2). In 2002, two large studies showed that people with breast cancer who underwent mini-lumpectomy combined with radiation therapy could live as long as those who underwent radical mastectomy. Further studies have shown that in lumpectomy, a “net margin” of only 2 mm of healthy tissue needs to be removed at the tumor margin. In 2009, the U.S. Preventive Services Task Force recommended that women should be screened for breast cancer with mammography starting at age 50 and every two years thereafter. This recommendation differs from the previous recommendation of annual screening starting at age 40. This change has sparked a major debate about the balance between the dangers of unnecessary treatment and the risks of undiagnosed cancer. In 2013, in a lawsuit between the Society for Molecular Pathology and Myriad Genetics, the U.S. Supreme Court overturned the molecular diagnostics company Myriad’s patent on the genetic code for BRCA1 and BRCA2. The judge’s statement of decision read, “Naturally occurring DNA fragments are the product of nature, not patents.” Although tests that detect specific deleterious mutations are still considered to fall within the scope of the patent. In 2015, in 2015, breast cancer survival rates reached an all-time high. Worldwide, more than 6 million breast cancer patients who have survived five years after diagnosis are still alive. This is despite the fact that breast cancer survival rates continue to lag in areas where advanced drugs are lacking. Current breast cancer treatment is individualized, combining surgery, chemotherapy and radiation therapy. Subsequent research will allow for more precise and less toxic treatment of breast cancer.