An Ancient Disease

From the time of the Pharaohs of ancient Egypt until the late nineteenth century, the standard treatment of breast cancer – if it was treated at all – was painful, brutal, and almost certainly ineffective. We know from the famous Edwin Smith Papyrus, a manuscript that dates from around 1,500 BCE, that ancient Egyptian physicians often left this disease untreated.

“This is a disease you should not treat,” was their advice to fellow physicians. Sometimes doctors did treat breast cancer with something called a “fire drill,” which was a cauterizing device that could destroy a small tumor and simultaneously drain accumulated fluids. This presumably burned away cancerous residues. The heat itself may have drawn white blood cells to the site, thereby constituting a primitive kind of hyperthermia or immunotherapy.

During the long centuries before the emergence of antimicrobial and anesthetic drugs, operations on the breast remained relatively rare. Treatment was generally by salves, ointments, and caustics (also known as escharotics), which might have helped with superficial tumors, but was unlikely to affect the regional or systemic disease.

Sometimes, in history, amputations of the breast were carried out (as can be seen in some gruesome medieval woodcuts). As Morris Shimkin, MD, the NCI historian of cancer treatment once wrote:

  • “The primitive and brutal amputations described in the older medical writings can be compared with the legend of the martyrdom of Saint Agatha,” a tortured figure familiar in medieval art (Shimkin 1979).

It is sobering to reflect on the generations of women who suffered, not just from this terrible disease, but from its brutal and largely ineffective treatment.

The Precursor of the Modern Approach

The precursor of the modern approach to breast cancer was the work of a pioneering French surgeon, Jean Louis Petit (1674-1750). Amazingly, his ideas of 300 years ago anticipated many of the features of the modern mastectomy: a wide excision (surgical removal of all or part of an organ, tissue, or structure) around the tumor, resection of the tumor itself, and the lymph nodes in the armpit, and evaluation of the connective tissues of the chest (the pectoral fascia).

In the 19th century, Charles H. Moore, MD, of Middlesex Hospital, U.K., pioneered the “en bloc” (meaning ‘as a unit’ or ‘altogether) resection of the primary tumor and its regional lymph nodes. He wrote:

Moore was clearly worried about spilling errant cancer cells into the bloodstream, where they could presumably progress to metastases. Despite such heroic efforts, however, breast cancer frequently did recur and the patient died. In the late 19th century, pathologists examining the tissues of afflicted patients made an unexpected finding: what seemed to be the progressive invasion of primary cancer to the major muscle groups and to the chains of lymph nodes in the chest. These discoveries provided the rationale for the most famous operation in the history of oncology, the radical mastectomy.

Enter William Halsted

The radical mastectomy is associated with the name of William Stewart Halsted, MD, (1854-1922), who first performed the operation in 1882 at Roosevelt Hospital, New York. He published on this development in 1891 and then, after moving to Johns Hopkins Hospital, Baltimore, in 1894 published a more complete exposition and tabulation of his results. Halsted later extended his operation to include the pectoralis minor muscle, i.e., the skeletal muscles of the chest wall that draw down the shoulder blades or raise the ribs.

At the time that Halsted described this procedure, the local recurrence rates of breast cancer surgery ranged from 50% to 80%. In one famous series, by the renowned European surgeon Theodor Billroth, MD, the recurrence rate was 82%! To everyone’s astonishment, Halsted’s case series of 50 patients included only three recurrences, or 6% of the total (Halsted 1891, 1894, and 1898). Even today this is hard to believe. In their day—coming from an eminent Johns Hopkins professor—these were electrifying reports.

Disease Free Survival

In Halsted’s final paper on the subject, 42.3% of patients were still alive at three years, which was also remarkable. By contrast, Billroth’s three-year disease-free survival rate was a mere 4.7%. Here, seemingly, was a triumph of American science and technology, on a par with Edison’s invention of the light bulb. Halsted’s secret was to remove all the tissue where cancer might recur. Thus, the whole breast, many lymph nodes, and muscles were cut away. Later, the operation was extended to include the application of radium tubes (an early version of the radiation treatment called brachytherapy).

After World War II, surgeons extended the radical mastectomy even further. The result was the so-called “super-radical,” the widest possible surgical operation for breast cancer. This combined Halsted’s radical mastectomy with the removal of chains of lymph nodes that were deep in the body and above the collarbone. While the goal was humane, there was a terrible price to pay for this procedure. This super radical procedure was pioneered at Memorial Sloan-Kettering Cancer Center (MSKCC) in New York City. Yet according to MSKCC breast surgeon, David Kinne, MD:

  • “This procedure was associated with an unacceptable morbidity and mortality rate but was typical of an era when surgeons, encouraged by improved anesthesia techniques and intra-operative and postoperative care, as well as by the support of blood banks and the availability of antibiotic coverage, designed wide-ranging, en bloc dissections” (Kinne 1991).

Residual Issues

Not only did the radical operation leave women with serious residual problems, such as lymphedema (swelling) of the arm, but they also were actually not as effective as surgeons hoped. A key question was often left unanswered: “Did extending the intensity of the treatment really increase overall survival rates? Or did it create more problems than it solved?” Very early, the question was raised as to whether or not aggressively extending surgery in this fashion really improved survival.

Because such radical procedures were highly controversial even in their day, randomized controlled trials (RCTs) were eventually carried out to test their effectiveness. To the chagrin of its advocates, rigorous trials failed to confirm any survival advantage for the extended radical mastectomy. Because of this, and a general trend towards more conservative surgery, the procedure was largely abandoned for early-stage disease. But for three-quarters of a century, Halsted’s ideas reigned supreme in North America. When the U.S. government’s “War on Cancer” began (in the early 1970s), few things seemed as certain as the necessity and effectiveness of this operation.

Concurrent Developments

Meanwhile, there were concurrent developments that were undermining the procedure. Some doctors began to wonder if a simple removal of the tumor itself would not be sufficient treatment in many cases, and that the removal of muscles and glands that characterized the Halsted radical was illogical and unnecessarily mutilating.

The less radical operations that were proposed included a simple mastectomy (removing just the breast, without underlying muscles or glands), quadrantectomy (removing the affected quarter of the breast), or lumpectomy (removing just the tumor (or lump) as well as a margin of normal tissue. Although these first came to most people’s attention in the 1980s, there had been a prominent advocate of limited surgery half a century before. This was Dr. Geoffrey Keynes of England, brother of the famous economist, John Maynard Keynes. In 1937, Sir Geoffrey wrote:

  • “Widespread operations…have no real justification and the idea of conservative treatment of cancer of the breast may become less repugnant to us [surgeons, ed.]” (Keynes 1937, emphasis added).

To aggressive surgeons, these were fighting words! Keynes had treated 325 women with local removal of the breast. He reported a 5-year survival rate of 71% for patients with stage I disease. This was comparable to what was being achieved at the time with radical mastectomy (Perez-Brady radiation textbook, p. 1358).

Vera Peters

A parallel challenge to Halsted came from advocates of radiation therapy. Keynes had also frequently implanted radium seeds at the site of the excision as well as in the armpit (axilla). But there were a few doctors who believed that radiation by itself, or possibly along with limited surgery, was a perfectly safe option for most women with early-stage breast disease. The best-known advocate of this position in North America was a pioneering radiotherapist, Vera Peters, MD, of the Princess Margaret Hospital, Toronto.

We look back today on Keynes and Peters as brave innovators. But at the time only a few doctors dared follow them in their breast-sparing approaches. Most prominent of these (but quite a few years later) was George Crile, Jr., MD, of the Cleveland Clinic, Ohio. He was the son of George Crile, Sr., a founder of that famous Cleveland Clinic. George Crile, Jr. became the first U.S. surgeon to advocate limited surgery for cancer in the breast. In fact, for around fifteen years, he was the only American surgeon to offer this option (Crile 1973). His popular book, What Women Should Know About the Breast Cancer Controversy, caused a furor when it was published in 1973, and many orthodox surgeons assailed it as a threat to women.

Change Was in the Air

But change was in the air. In the 1960s, a young surgeon named Bernard Fisher, MD of Pittsburgh, organized the first randomized controlled trial (RCT) to compare radical vs. conservative treatments (Fisher 1977). The results of this and other large clinical trials were to finally prove that for most patients lumpectomy plus radiation yielded the same survival rates as the extended Halsted radical.

It is hard for us now to recall how courageous it was to perform this trial. As a former cancer surgeon explained:

  • “For the first time in history, surgeons did a study in which cancer cells were knowingly left behind, untreated within the lymph nodes of some patients. In some patients (about 20% of them) these cancer cells did grow and the cancer-containing lymph nodes had to be removed, several months after the original surgery. Surprisingly, patients treated in this way lived just as long as patients who had their lymph nodes removed at the time of mastectomy” (Evans 2000)

But that was not all:

  • “The study concluded that surgeons could prudently leave a small number of cancer cells within a patient’s lymph nodes without threatening her survival. The study further concluded that these cancer cells could grow into a sizable tumor mass…large enough to be felt by the doctor. Allowing tumor cells to grow untreated within a patient seemed contrary to all known principles of sound cancer treatment. It may have been risky, but it proved an important point. This study was greeted with dismay and hostility by many surgeons” (Evans 1980 and Evans 2000).

Lumpectomy Plus Radiation

Eventually, however, the combination of lumpectomy plus radiation was accepted by the NCI and the medical profession as a reasonable choice for most cases of early-stage breast cancer. The radiation was usually given in doses of 45 to 50 Gy, with a further 10 Gy radiation “boost” to the tumor bed. Most textbooks on cancer treatment in fact now recommend this treatment.

Once this combination was accepted, a few people wondered about the relative contribution of the two modalities to the results. In particular, some people wondered what exactly was radiation’s contribution. Was it possible that radiation, for all its apparent benefit, did not appreciably increase the overall survival of the women who received it?

We hope to explore that question in future writings.