Finally, it is to be noted that 15 years have passed since the spectrum thesis was first introduced. During that time, it has not been subjected to verification. Consequently, no scientific evidence has been presented to challenge the alternative hypothesis, any of its tenets, or the paradigm that currently governs the treatment of breast cancer.

Another aspect of the criticism of our alternative hypothesis is that associated with the concept of oligometastases. According to Rabinovitch and Kavanagh, that construct is “an intermediate phase of cancer progression falling somewhere between the hypotheses of Halsted and of Fisher,” and by “targeting limited and measurable sites of metastatic disease,” more favorable disease-free and overall survival will result. Rabinovitch and Kavanagh claim that “This concept has already been evaluated in prospective clinical trials with provocatively encouraging results to date.”

The initial description of oligometastases by Hellman and Weichselbaum, in their 1995 Journal of Clinical Oncology editorial, was more complex. They conveyed the “thought processes” that resulted in their oligometastases thesis in a series of statements, such as the following:

 
• “... there are tumor states intermediate between purely localized lesions and those widely metastatic. Such clinical circumstances are not accounted for by either the contiguous [Halsted] or the systemic [alternative] hypotheses. [In both of those theses, when metastases occurred,] they were ‘extensive and widespread’.”
• “From considerations of these theories of cancer dissemination, in the light of the emerging information on the multistep nature of cancer progression, we propose the existence of a clinical significant state of oligometastases. For certain tumors, the anatomy and physiology [host factors] may limit or concentrate these metastases to a single or a limited number of organs.”
• “The likelihood of the oligometastatic state should correlate with the biology of tumor progression, rough clinical surrogates of which, for many tumors, might be primary tumor size and grade” [tumor factors].
• “Metastasizing cells may seed specific organs as a function of the seeding tumor cell number and characteristics as well as the receptivity of the host organ [tumor and host factors].”
• “The importance of ‘seed and soil’ [tumor and host factors] have [sic] been considered elsewhere. ... “
• “An attractive consequence of the presence of a clinically significant oligometastatic state is that some patients so affected should be amenable to a curative therapeutic strategy.”

None of the above statements present new concepts, data, or biologic information related to the influence of host and tumor factors on metastases that might justify considering replacement of any of the tenets comprising the alternative hypothesis. Some, in fact, even support the tenet of our hypothesis, which indicates that “complex host-tumor interrelationships affect every aspect of the disease” (Table 2).

The idea that some patients may have a single or a few metastases that “should be amenable to curative therapeutic strategy” by stereotactic body irradiation (SBRT) or other targeted therapies seemed, in 1995, and perhaps remains to this day, worthy of further consideration. However, until the value of such therapies is proven by current laboratory and clinical research strategies, their biologic and clinical significance remains tenuous. Although Rabinovitch and Kavanagh state in their editorial that information has been obtained from prospective clinical trials with “provocatively encouraging results to date,” the article that they refer to [Milano et al] provides data that is less convincing. Findings reported in that article were not obtained from clinical trials but, rather, from anecdotal reports from only 40 patients with five or fewer metastatic lesions who were treated by SBRT with curative intent and from only 11 patients who were similarly treated with palliative intent. Although a plethora of findings were obtained from those few women, Milano et al41 also noted that “Additional studies are needed to further explore SBRT for oligometastatic disease from breast cancer.” They also noted that “... longer follow-up is needed to confirm the hypothesis that oligometastatic disease is potentially curable with multimodality therapy [chemotherapy and hormonal therapy] incorporating local treatment” [SBRT]. Finally, in contrast to Rabinovitch and Kavanagh’s contention, Milano et al state that “... our results do not compellingly support the hypothesis that decreasing disease bulk in patients with breast cancer has the potential to reduce distant metastatic progression.”

Before the publication of that report, Hellman had appropriately stated that, “The limited effectiveness of these treatments of oligometastases has been primarily the result of an inability to recognize all metastases and the fact that these seemingly limited lesions were too often a manifestation of undetected widespread cancer. The importance of oligometastases depends on how commonly they are present.”) He reinforced that admonition by stating further that “Effective treatment of oligometastases will require identification of all of the lesions and, most importantly, of the state of intermediate tumor progression likely to be consistent with the oligometastatic state.”

Unfortunately, those issues have not been resolved and, in fact, have become more complex. As a result of improving technology, an increasing number of reports demonstrate that “... tumor cell dissemination starts already [sic] early during tumor development and progression,” and that “Tumor cells are frequently detected in the blood and bone marrow of cancer patients without clinical or even histopathologic signs of metastasis.” The statements noted above fail to completely address the issues of identifying and removing not only all metastases, but dormant tumor cells and stem cells as well. Overlooked by those who promote the oligometastases concept is the report by one of us (B.F.) in 1959 that provided experimental evidence about the dormant tumor cell. In that report, I concluded that, “... cancer cells, alive to begin with, may be enduringly capable of growth if conditions are favorable.” Finally, 15 years have passed, and, as with the spectrum thesis, the oligometastases hypothesis has not given rise to a new paradigm for governing the treatment of breast cancer.