New research showing that certain women with early-stage breast cancer may be able to skip chemotherapy has created understandable excitement: Avoiding the side effects of chemotherapy without compromising one’s prognosis is highly appealing for women diagnosed with this difficult disease. Interestingly, such an approach would have been of little surprise to a group of largely forgotten 20th-century physicians who vehemently argued that breast cancers had distinctive biologies and therefore needed different treatments. It is worth revisiting the recommendations of these pioneering clinicians, and the scorn they received, as we incorporate this new research into daily clinical practice.
The treatment of choice for breast cancer in the early 1900s was the radical mastectomy, popularized by Johns Hopkins University surgeon William Halsted. The operation, which involved the removal of the affected breast, nearby lymph nodes, and both chest-wall muscles on the side of the cancer, was drastic, but it was believed to be the only chance that a woman could survive. In some instances, aggressive radiation therapy was added to the surgery to try to kill additional cancer cells. (Chemotherapy did not become widely available until the 1970s.)
This treatment of breast cancer was uniform, but certain physicians began to do research suggesting that not all cases of the disease were the same. For example, a 1925 study by Boston surgeon Robert B. Greenough identified three different types of cancers under the microscope: those of low, medium, and high malignancy. Whereas 68 percent of those with low malignancy survived five years, none of those with high malignancy survived. Medium malignancy gave an intermediate survival rate of 33 percent.
But it was not until the 1950s that a group of physicians, loosely unified under the name “biological predeterminists,” began to argue that treatment of the disease should reflect its microscopic characteristics and its apparent spread. The term biological predeterminism was likely coined by an iconoclastic Los Angeles physician named Ian MacDonald who had trained in pathology, radiotherapy, and surgery. In a 1951 paper, MacDonald argued that full-scale surgery and radiotherapy did not make sense either for cancers that looked nonaggressive (and would likely not metastasize) or very aggressive (and would likely be lethal regardless of the treatment). “Rigid ideas of prognosis in terms of duration and dimension,” MacDonald wrote, “should be abandoned in favor of an attempt to evaluate the biological potential of a neoplasm in an individual host.”
Ironically, MacDonald, who was a visionary in the world of breast cancer, firmly rejected the idea that cigarettes caused lung cancer and continued to smoke. He died in 1968 from a fire started by a cigarette.
Adding to MacDonald’s work was research by New York pathologist Maurice M. Black. Focusing on the nuclear grade of cancer cells, Black argued that microscopic examination of breast cancers revealed their biology and could be used to guide treatment. Even more notably, in retrospect, was Black’s suggestion that findings on microscopic exams could also reveal how well a woman’s own body was fighting her breast cancer, a concept that foreshadowed modern cancer immunotherapy.
Fellow physicians often reacted to MacDonald, Black, and the other predeterminists with disdain. The post–World War II era was the beginning of the modern “war on cancer,” and only the most aggressive therapies seemed able to obliterate the enemy of cancer, much as the Allies had outfought their opponents. One breast specialist noted that the best surgeons had a “sharp knife,” a “stout heart,” and “unquenchable optimism.”
In this climate, those emphasizing biology—and the notion that many women could safely skip radical mastectomy in favor of smaller operations—were criticized as nihilists. “Therapeutic defeatism,” dismissingly wrote one set of authors in 1957, “is the fashion.” The following year, another group of physicians argued that the focus on biology was “confusing and demoralizing” to young physicians beginning their careers. Privately, many surgeons believed that the predeterminists, with their overemphasis on biology and statistics, were killing women.
In retrospect, of course, the predeterminists largely had it right. What modern research has confirmed is that breast (and other) cancers have a distinctive genetic makeup that helps to determine their biological potential. As Maurice Black suspected, knowledge of this biology can help guide treatments, making them more aggressive when necessary and milder when warranted.
Invoking biology to guide cancer prognosis and treatment is no longer heretical. The New England Journal of Medicine study cited above indicates that as many as 70 percent of patients with early-stage breast cancer do not need chemotherapy—and there has been no apparent backlash by the oncologists who administer these drugs, nor by the companies that make them. But don’t think for a moment that the current culture of cancer is so different from the 1950s. Despite many an article and book bemoaning our overuse of the war metaphor, women with breast cancer are still often referred to as courageous soldiers fighting their disease, even though this mindset harms the very women attempting to navigate their diagnoses.
It is the challenge of modern clinicians and patients to work together to process and incorporate the radically new approach to breast-cancer treatment that these—and likely future—studies portend. Biology may be key, but we still must process it as a society.