The need for a new way of looking
The rationale behind the original and continuing development of mammography is a simple one, common to all cancer screening methods – the belief that the earlier the detection of a cancer, the more likely it is to be treated effectively with the therapeutic regimens at hand. While there is some controversy regarding the cost-benefit ratio of screening, especially when therapies for breast cancer are not perfect and vary widely in expense and availability globally, the driving belief has been that mammography provides an outcomes benefit in allowing early surgical and chemoradiation therapy with a curative intent.
There were two main driving forces behind the early development of mammography. The first was the highly lethal nature of breast cancer, especially when it was caught too late and had spread too far to benefit from the only available option at the time – surgery. The second was the severity of the surgical treatment, the only therapeutic option at the time, and the distressing number of women who faced the radical mastectomy procedure pioneered by physicians(1852-1922) at Johns Hopkins University, Baltimore, and (1858-1932) in New York.
In 1894, in an era when the development of anesthetics and antisepsis made ever more difficult surgical procedures possible without inevitably killing the patient, both men separately published their results of a highly extensive operation that consisted of removal of the breast, chest muscles, and axillary lymph nodes.
As long as there was no presurgical method of determining the extent of a breast cancer’s spread, much less an ability to visually distinguish malignant from benign growths, this “better safe than sorry” approach became the default approach of an increasing number of surgeons, and the drastic solution of radical mastectomy was increasingly applied universally.
But in 1895, with the discovery of x-rays, medical science recognized a nearly miraculous technology for visualizing the inside of the body, and radioactive materials were also routinely used in medical therapies, by both legitimate practitioners and hucksters.
However, in the very early days, the users of x-rays were unaware that large radiation doses could have serious biological effects and had no way of determining radiation field strength and accumulating dosage.
In fact, early calibration of x-ray tubes was based on the amount of skin reddening (erythema) produced when the operator placed a hand directly in the x-ray beam.
It was in this environment that, within only a few decades, the new x-rays, especially with the development of improvements in mammography imaging, were able in many cases to identify smaller, more curable breast cancers. This eventually allowed surgeons to develop and use less extensive operations than the highly disfiguring radical mastectomy that was simultaneously dreaded for its invasiveness and embraced for its life-saving potential.4
The technological history of mammography was thus driven by the quest for better imaging and reproducibility in order to further the hopes of curative surgical approaches.
In 1913, the German surgeon(1883-1976) was the first to detect breast cancer using x-rays, but its clinical use was not established, as the images published in his “Beiträge zur pathologie und klinik der mammakarzinome (Contributions to the pathology and clinic of breast cancers)” were photographs of postsurgical breast specimens that illustrated the anatomy and spread of breast cancer tumors but were not adapted to presurgical screening.
After Salomon’s work was published in 1913, there was no new mammography literature published until 1927, when German surgeon Otto Kleinschmidt (1880-1948) published a report describing the world’s first authentic mammography, which he attributed to his mentor, the plastic surgeon Erwin Payr (1871-1946).5
This was followed soon after in 1930 by the work of radiologist(1896-1981), of the University of Rochester (N.Y.), who published a paper on the use of standard roentgenograms for the in vivo preoperative assessment of breast malignancies. His technique involved the use of a stereoscopic system with a grid mechanism and intensifying screens to amplify the image. Breast compression was not involved in his mammogram technique. “Dr. Warren claimed to be correct 92% of the time when using this technique to predict malignancy.”5
His study of 119 women with a histopathologic diagnosis (61 benign and 58 malignant) demonstrated the feasibility of the technique for routine use and “created a surge of interest.”6
But the technology of the time proved difficult to use, and the results difficult to reproduce from laboratory to laboratory, and ultimately did not gain wide acceptance. Among Warren’s other claims to fame, he was a participant in the Manhattan Project and was a member of the teams sent to assess radiation damage in Hiroshima and Nagasaki after the dropping of the atomic bombs.
And in fact, future developments in mammography and all other x-ray screening techniques included attempts to minimize radiation exposure; such attempts were driven, in part, by the tragic impact of atomic bomb radiation and the medical studies carried out on the survivors.
An image more deadly than the disease
Further improvements in mammography technique occurred through the 1930s and 1940s, including better visualization of the mammary ducts based upon the pioneering studies of Emil Ries, MD, in Chicago, who, along with Nymphus Frederick Hicken, MD (1900-1998), reported on the use of contrast mammography (also known as ductography or galactography). On a side note, Dr. Hicken was responsible forin 1937.
Problems with ductography, which involved the injection of a radiographically opaque contrast agent into the nipple, occurred when the early contrast agents, such as oil-based lipiodol, proved to be toxic and capable of causing abscesses.7This advance led to the development of other agents, and among the most popular at the time was one that would prove deadly to many.
Thorotrast, first used in 1928, was widely embraced because of its lack of immediately noticeable side effects and the high-quality contrast it provided. Thorotrast was a suspension of radioactive thorium dioxide particles, which gained popularity for use as a radiological imaging agent from the 1930s to 1950s throughout the world, being used in an estimated 2-10 million radiographic exams, primarily for neurosurgery.
In the 1920s and 1930s, world governments had begun to recognize the dangers of radiation exposure, especially among workers, but thorotrast was a unique case because, unbeknownst to most practitioners at the time, thorium dioxide was retained in the body for the lifetime of the patient, with 70% deposited in the liver, 20% in the spleen, and the remaining in the bony medulla and in the peripheral lymph nodes.
Nineteen years after the first use of thorotrast, the first case of a human malignant tumor attributed to its exposure was reported. “Besides the liver neoplasm cases, aplastic anemia, leukemia and an impressive incidence of chromosome aberrations were registered in exposed individuals.”8
Despite its widespread adoption elsewhere, especially in Japan, the use of thorotrast never became popular in the United States, in part because in 1932 and 1937, warnings were issued by the American Medical Association to restrict its use.9
There was a shift to the use of iodinated hydrophilic molecules as contrast agents for conventional x-ray, computed tomography, and fluoroscopy procedures.9 However, it was discovered that these agents, too, have their own risks and dangerous side effects. They can cause severe adverse effects, including allergies, cardiovascular diseases, and nephrotoxicity in some patients.