Part 1. Differences between Europe and the USA.
Real or Only Apparent?
During the 1920s and 1930s, radiation therapy of chronic mastitis --- with good results --- was reported from Europe. However, there were almost no articles on this therapy of chronic mastitis in the American literature. This is so out of keeping with the reporting of other disorders treated with x-ray, that we have been looking for an explanation.
Was the practice really absent in the United States --- or was there only a reluctance to write about it here?
This is not "just an academic question." When used, this therapy delivered about 375 Roentgens to the irradiated breast (Part 6). Moreover, chronic mastitis appeared to occur far more frequently than acute mastitis (see below). So we must explore various aspects of chronic mastitis in this chapter.
What Is Chronic Mastitis?
Chronic mastitis is one name given to a group of disorders. They have received many names at different times and in different countries of the world. It took a long time to sort out the reality of any differences within this broad grouping of diseases, but it was finally agreed in most quarters that the entity, chronic mastitis, is a single disease with multiple features of manifestation. Cases differ from each other with respect to the prominence and frequency of various signs. At a given time, some cases will prominently display one set of signs; other cases will prominently display others. And with the passage of time, a particular case may shift in the relative prominence of the various possible manifestations.
The real issue, widely discussed and argued, was whether this disorder was really a benign tumor of the breast, or whether it was a chronic inflammatory disease. And if it was chronic inflammation, was it a prelude to malignancy? The various names under which this single disease was listed reflected, for a particular time and place, the leaning of the medical profession toward inflammatory disease or toward benign neoplastic disease.
In 1947, Drs. George Pfahler and George Keefer reported on use of radiation therapy for chronic mastitis in their own Philadelphia (Pennsylvania) practice. In their paper, they described the multiple names for the disease (p.1352, p.1354):
"It has been described as chronic mastitis, mazoplasia, chronic cystic mastitis, fibrocystic mastitis, adenofibrosis, and Schimmelbusch's disease, but Ewing [a great American pathologist] concluded that it begins as an inflammatory process, and then passes through these various changes into carcinoma."
Chronic Mastitis: Far More Frequent Than Acute Mastitis
Swedish physicians appear to have used two designations for this disease, fibroadenomatosis and chronic mastitis. In an earlier work (Gofman 1981), we summarized the report from Sweden by Baral et al (1977) on cases of chronic mastitis/fibroadenoma treated with radiation between 1927 and 1957 at the Radiumhemmet of Sweden.
We found in the Baral Study that fibroadenomatosis and chronic mastitis together added up to 904 total cases, whereas acute mastitis accounted for only 120 cases. That is a ratio of over 7 to 1. It makes the scarcity of American reports on radiation therapy of chronic mastitis all the more striking. We all know that disease rates can vary from one country to another, but is that the explanation?
Roentgen Therapy for Inflammatory Conditions --- with This Exception?
The scarcity of American reports on roentgen therapy for chronic mastitis (and its various names) is particularly puzzling during years when American roentgenology was reporting success treating the inflammatory response in many other situations (see Chapters 13, 18, 33, 34, and 36). Is there any reason that radiation therapy specifically for chronic mastitis might have been avoided? Or might a widespread use of it have been a `verboten' subject in U.S. medical literature? We will consider some possibilities as the chapter progresses.Part 2. Saving a "Lumpy" Breast versus Missing a Cancer
Chronic mastitis presents itself in several manifestations. Sometimes the prominent feature is recurrent pain and tenderness in the breast, particularly associated with menstrual periods. In some cases, multiple nodules (some tender) are found in both breasts. And sometimes there is even some secretion from the breast, which is worrisome to the observer. Even though Ewing suggested that these features are part of a picture of a disease which ends up as carcinoma of the breast, it is quite clear from the literature that the features of this disease do not justify a diagnosis of breast-cancer.
But this disease can present physician-observers with a potentially serious problem. The signs and symptoms are not diagnostic of cancer. And any decent physician would surely think of conservation of breasts with a set of signs and symptoms which are not those of malignancy. But physicians know very well that they can not exclude a small carcinoma hidden in a breast which is laden with the lesions of chronic mastitis. Drs. Pfahler and Keefer (1947) stated it well (p.1352):
"We realize that clinical judgment or clinical diagnosis without biopsy or mastectomy cannot be absolutely reliable. Neither can a small amount of tissue removed in these cases for microscopic study or puncture biopsy be reliable for Cheatle has shown that carcinoma is more apt to be found in the small nonpalpable cysts than in the larger ones, and that removal of a large cyst for diagnosis may leave the small carcinomatous cyst in the breast."
And they add: "On the other hand, one is not justified in recommending a mastectomy in every lumpy breast."
The Urge to Stay out of Trouble versus Breast-Conservation
We think this situation was accompanied by a real dilemma for physicians. It would take courage to say to a woman, "We shall watch it, or treat it with radiation for the inflammatory process."
The "what if" is obvious. The physician must think, "There just might be a small cancer developing among those lesions. And if no biopsy or mastectomy is performed, what will I be able to say if one of these women comes back later with a frank carcinoma --- for which, in retrospect, I should have recommended biopsy or mastectomy? Won't I be severely criticized and vulnerable to a lawsuit? After all, there was prior literature suggesting that chronic mastitis ultimately can end up as a breast-cancer."
But sensitive physicians also must have considered the worth to their female patients of keeping their breasts. It is not a very sensitive physician who would say, "Why not get rid of that breast, so it cannot cause trouble!"
Physicians who believed that biopsy and/or mastectomy could be avoided with safety for almost all patients with chronic mastitis, by treating the condition with radiation therapy, probably felt "way out on a limb." They may have worried a lot about what the critics and lawyers would say if and when one of these cases did indeed develop overt cancer of the breast.Part 3. Were Women with Chronic Mastitis Afraid to Visit Physicians?
Obviously, the Swedish Radiumhemmet was accumulating a large series of cases of non-malignant diseases of the breast, treated between 1927 and 1957 with radiation without surgery, as reported by Baral 1977. Quite possibly the Swedish culture permitted a leading institution to try to save breasts where it was deemed possible, without huge penalties or disgrace to the physicians.
In Britain by 1928, there had been impassioned articles pleading for the preservation of breasts in cases of chronic mastitis. For example, in the July 14, 1928, issue of the Lancet, J.H. Douglas Webster wrote a strong case for radiation therapy of chronic mastitis, which he entitled "Radiology and Surgery in Cancer of the Breast and in `Chronic Mastitis'." In his paper, Webster also suggested that some women with chronic mastitis might stay away from medical facilities --- to the women's detriment --- out of fear that breast surgery would be recommended. He wrote (p.65):
"It is an unfortunate tradition among patients that anything wrong with the breast probably means an operation, and I am convinced from many inquiries that the fear of operation is largely responsible for the high percentage of patients who come for treatment not in an operable stage, much less a `mastitis' stage, but in a frequently inoperable and, so far as we know at present, a practically hopeless condition."
Successes Reported from Radiation Therapy of Chronic Mastitis
In Britain, Reynolds (1932) reported in "Proceedings of the Royal Society of Medicine" a favorable experience in treating 150 cases of chronic mastitis with x-rays.
In Norway, Engelstad and Weyde reported (1944) on a series of successful treatments of "Adenofibrosis Mammae" (in the Norwegian Radium Hospital's material, 1932-1942). Roentgen therapy was used in 123 patients with a favorable outcome in the majority.
In the USA, Drs. Howard C. Taylor and Robert L. Brown (Taylor 1938) commented that "Detailed reports on the effect of roentgen irradiation on chronic mastitis are almost absent in the medical literature." They also stated that "Selected cases of chronic mastitis have been treated by direct roentgen irradiation for several years at the Memorial Hospital [New York City]. It has remained a method to be used only in patients with severe or persistent symptoms." They did not say how many, or what fraction of cases, were treated by radiation there.
"Improvement" was reported by Taylor and Brown as follows: "... that large doses of roentgen rays do have a definite effect on non-malignant diseases of the breast can best be shown by the unilateral improvement in symptoms and reduction in size when one breast is treated and the other kept untreated as a control." Such a comparison was made at Memorial Hospital in one case, reported at p.519.
Finally, in 1947 Pfahler and Keefer published their first paper on this subject. They reported on 151 cases, accumulated between April 1920 and May 1946, of women treated with radiation therapy for chronic mastitis. It is interesting that Dr. Pfahler was one of the earliest radiologists in America --- and quite obviously, Dr. Pfahler thought well enough of this therapy to stay with it for a very long time.Part 4. A Strong Recommendation from 1947: Consult with a Surgeon
Notable in the Pfahler/Keefer paper of 1947 is the repeated emphasis on the fact that Dr. Pfahler consulted with surgeons on most of his cases, before going ahead to treat the patients with x-rays. At page 1352:
"During the past twenty-five years --- April, 1920 to May, 1946 --- one of us (Pfahler) treated 151 cases in which the clinical diagnosis was chronic mastitis. In nearly all of the cases the opinion of an experienced surgeon was also obtained. In some cases the patients were sent by the surgeons because they did not feel justified in operating; on the other hand, they did not want to ignore the condition on account of the commonly associated chronic mastitis and carcinoma." And at page 1354:
"There is much danger of mistaking carcinoma for chronic mastitis; therefore, we urge that so far as possible each case be observed or diagnosed by conference between the surgeon and the radiologist, and if in doubt, a biopsy or mastectomy be advised."
In our opinion, Pfahler and Keefer were sending a very clear message to other physicians: "Watch out, there will be criticism of choosing radiation therapy for chronic mastitis, and you should cover your bases with an experienced surgeon, lest there be lawsuits over cancers missed."
What Happened to the Pfahler/Keefer Patients?
Drs. Pfahler and Keefer reported that they did not find a large incidence of breast-cancer in their 151 treated cases. One case only. At p.1352, they stated:
"From the fact that only one of our series of 151 patients with diseased breasts developed cancer of the breast, we must conclude that the clinical diagnoses were extraordinarily accurate or the treatment prevented the development of carcinoma in some of these cases." We need not question this, since the follow-up times were certainly not long enough to ascertain the true breast-cancer rate in the group. Out of 151 treated cases, the follow-up times only on those reported as "Well and symptom-free" were given. These represented 111 of the 151 total cases:Duration of Follow-Up Number of Cases Percent 1 year or less 34 30.8 % 1 to 5 years 33 29.0 % 5 to 10 years 17 15.8 % 10 to 25 years 25 22.6 % Over 25 years 2 1.8 %Part 5. The Possibility of a Big Underestimate in Breast-Dose
We see two possibilities worth discussion.
First: The frequency of radiation therapy in America for chronic mastitis, in the 1920-1960 era, may have been at the low level reflected in the 1947 paper by Drs. Pfahler and Keefer --- a frequency which would then represent a very small contribution to x-ray exposure in our Master Table, Column F. This would be good news. On the other hand, we are left to wonder if fear of malpractice suits may have meant that many thousands of women with chronic mastitis lost their breasts unnecessarily.
Second: The possibility exists that radiologists, trying to help women conserve their breasts, silently did a lot more radiation therapy for chronic mastitis than they ever wrote about in the medical journals. After all, at the time, total doses of 400 Roentgens were considered to be harmless (see Index: Safety assurances). So it may have been hard for physicians to deny the women a presumably harmless treatment which seemed to relieve the pain and tenderness and which conserved the breasts. But such physicians may not have wanted to issue an invitation to criticism and lawsuits by writing about it.
If radiologists were using a lot more x-ray, silently, for chronic mastitis, we would certainly want to assess it appropriately in our Master Table, but there is no available way for us to assess it. Following our intention to reach a credible lower limit on breast-dose, we will base our estimate on the first possibility discussed above.
In addition, we will assume that no one in Philadelphia except Dr. Pfahler ever used radiation therapy to treat chronic mastitis. This Pfahler-only assumption almost certainly leads to an underestimate in the entries for Column F of our Master Table.Part 6. Quantitative Analysis for the Master Table, Column F
o - Item 1: To obtain the dose-estimate from treatment of chronic mastitis, we will use the Pfahler-Keefer series of 151 women treated in the private practice of Dr. George Pfahler, Philadelphia, Pennsylvania (Pfahler 1947), between April 1920 and May 1946 (26 years).
o - Item 2: Do these 151 cases represent the total number of treated women in Philadelphia during those years? Probably not. By using the assumption that they represent the total, we operate in the direction of underestimating nationwide person-rads from treatment of chronic mastitis.
Women of Each Age-Year Irradiated per Calendar-Year
o - Item 3: We shall arbitrarily assign equal numbers of women treated to each age-year, from age 20 through 54 years, in the absence of information to the contrary. The 151 irradiated women, distributed into 35 separate age-year categories, become 4.31 women per age-year. And since these studies were conducted over a period of 26 years, the annual number of women treated, on average, was (4.31 / 26), or 0.166 per age-year annually.
Females of Age-Years 20-54, per Year, USA and Philadelphia
o - Item 4: We will estimate Philadelphia's population of women in each age-year, for an average year in the 1920-1960 period, in our usual manner. We begin with the ratio of the Philadelphia population to the U.S. population in 1960:
The ratio was: Philadelphia / USA = 2,002,512 / 179,333,000.
This ratio we take as valid over the 1920 - 1960 interval.
Then we find the national number of women per age-year in the Master Table, Column A, and we multiply each value by the ratio. To simplify, we will use one value for an entire age-band, and tabulate below.National Number Philadelphia Age-Band per Age-Year Number per Age-Year 20-24 884,794 9,880 25-29 881,805 9,847 30-34 878,278 9,807 35-39 873,473 9,754 40-54 852,293 9,517
Breast-Dose per Treated Woman
o - Item 5: We need the average dose to breast-pairs from the therapy. The average entrance dose was 375 Roentgens, total, delivered in six separate doses.
This total needs conversion to rads. The usual conversion factors for various beam-directions are shown in Chapter 23, Part 3. For front-to-back beams, we will use 0.693 breast-rads per Roentgen. Thus, (375 R) x (0.693 rads / R) = 260 rads. So, each of the six exposures was about 43.3 rads. A downward adjustment per exposure is required for supra-linear dose-response, as discussed in Chapter 8, Item 8. The adjustment factor for 40 rads is 0.594. In addition, we do not know that the entire breast-area was exposed. We will assume that only half was exposed, and adjust downward by a factor of 0.5 too. So the average adjusted breast-dose per treated woman would be: (260 rads) x (0.594) x (0.5) = 77 rads (rounded off).
Conversion of Individual Dose to Population-Dose
o - Item 6: We need the average population-dose from this therapy, rather than the raw individual dose per treatment. We use our customary two-step process: Person-rads, and then person-rads divided by total persons. We can do it all in the tabulation which follows.Treated Total Annual Age- Women Dose in Person- Women Population- Band, per Medical Rads in Each Dose per Years Age-Year Rads Age-Year Age-Year 20-24 0.166 77 12.78 9,880 0.0013 25-29 0.166 77 12.78 9,847 0.0013 30-34 0.166 77 12.78 9,807 0.0013 35-39 0.166 77 12.78 9,754 0.0013 40-54 0.166 77 12.78 9,517 0.0013
o - Item 7: Duration. We will make no adjustment for duration, because there is nothing in the Pfahler-Keefer paper of 1947 which suggests termination of such treatments after 1946. And the fact that 60% of the patients have follow-up times shorter than 5 years (Part 4, above) suggests that much of the treatment was recent.
In any case, we are talking about very small entries to Column F of the Master Table from therapy of chronic mastitis, as long as we accept the assumptions adopted in Part 5 of this chapter --- assumptions which may result in a serious underestimate of dose from such therapy.
# # # # #
Excerpts (Part 2) from an Important Paper of 1931:
Dr. Desjardins asked: "Why is irradiation not used more than it is?"
"The evidence of the therapeutic value of irradiation in inflammatory processes is so abundant and the testimony is so generally favorable that one wonders why irradiation is not used more than it is. Perhaps the very multiplicity of inflammatory lesions in which radiotherapy has been claimed to be effective has led to a not unnatural skepticism. Or, again, failure to utilize the treatment may be due to the excessive fear of ill effects, a fear springing probably from the reading of reports of injury, occurring during treatment for malignant tumors with large doses of irradiation, or of the systemic reaction which so often follows irradiation for lesions requiring prolonged exposure. However, the treatment of inflammatory processes, especially the acute conditions, is an entirely different affair, as will appear presently."
And also he asked (p.404): "What is the mode of action of irradiation?"
"Various explanations have been advanced to account for the influence of the rays on inflammatory conditions, and the very multiplicity of such explanations probably has led many physicians to discredit the clinical evidence or to ascribe it either to overenthusiasm or to psychic factors. Indeed, without a satisfactory and convincing explanation it would be difficult to believe that the same agent could be therapeutically effective against so many different forms of inflammation in different organs or parts of the body. And yet the reason appears to be quite simple and rests on sound and abundant experimental evidence. The natural tendency would be to think that the effect of the rays on inflammatory lesions may be due to a bactericidal action on the infecting organisms, but the almost constant negative results of the large number of experiments undertaken to test the direct influence of irradiation on many kinds of bacteria render such an hypothesis untenable. Since irradiation acts in much the same way and in almost exactly the same time on so many forms of acute inflammation, it is obvious that the inflammatory lesions must have some common factor. What may this factor be?"
The remainder of this paper is devoted to a careful analysis of the world-wide studies of the action of roentgen rays and radium on cells, and of the powerful evidence that the lymphocyte is by far the most radio-sensitive cell. But then, Desjardins asks how does this relate to an action in suppression of the inflammatory process? Much excellent and insightful reasoning leads Desjardins to the conclusion that the roentgen irradiation acts by destroying lymphocytes infiltrating the inflammatory lesion or circulating in the blood vessels which supply the affected area. Why would this have a therapeutic effect? Desjardins suggested that the infiltrating cells contain or elaborate within themselves the protective substances or other means which enable them to destroy or neutralize the bacterial or other toxic products which give rise to to the defensive inflammation. And he states:
"If these assumptions are well founded, it seems not unreasonable to deduce that irradiation, by destroying the infiltrating lymphocytes, causes the protective substances contained by such cells to be liberated and to be made more readily available for defensive purposes than they were in the intact cells. There can be little question that the rays act by destroying the infiltrating leukocytes and that the value of radiotherapy depends chiefly on such action."
Whether every idea of Desjardins proved to be correct is not the question at all. It is a beautiful phenomenon to see a critical scientific mind marshalling the worldwide experimental literature plus his extensive clinical experience on this issue, in seeking to understand mechanism of action. It is self-evident, in this author's opinion, that Desjardins was not dealing with an illusion. Moreover, the problem was important. Over time, from staphylococcus to pneumococcus, inflammatory diseases have killed millions.