In these two statements, Hellman, and, consequently, Rabinovitch and Kavanagh, indicate that because breast cancer is considered by me (B.F.) to be a systemic disease, I believe that “local control… is unimportant to survival” and “that local eradication of disease makes no difference.” The impropriety of both of those statements, which seem to be a fundamental basis for their criticism, has already been extensively addressed in this commentary (Locoregional Recurrence).

  * “Nodal involvement [according to the alternative hypothesis] is not an orderly contiguous extension, but rather a marker of distant disease.

This statement seemingly relates to the manner in which tumor cells spread from a primary tumor. It was Halsted’s view that tumor cells did not disseminate via the bloodstream but, instead, traversed lymphatics to lymph nodes by contiguous [touching each other] extension. Those nodes then became the source of distant tumor spread, also by contiguous extension via the lymphatics. Halsted viewed the lymph node as a “way station” on the road to distant disease. The alternative hypothesis, on the other hand, has contended, based on experimental findings, that metastases are the result of disseminated tumor cells via both the blood and lymphatic systems, which are so interrelated that a specific route of dissemination is highly unlikely. Thus the view that the lymph node (and not the tumor in the breast) is the initial source of metastasis seems implausible. Contrary to Hellman’s interpretation of our thesis, it has never been denied that an unremoved tumor-bearing lymph node could be a source of further tumor spread. Moreover, we have clearly stated that, “The lymph node that contains tumor cells is important in that it reflects an interrelationship between host and tumor that permits the development of metastases rather than that it is an [the initial] instigator of distant disease.” With regard to the statement that we think that positive lymph nodes are markers of distant disease, we have previously shown that a positive lymph node is an indicator (marker) of the probability of distant disease. We first demonstrated a relationship between the number of positive nodes (one to three v four or more) and the prognosis of a patient.

  * “While lumpectomy plus radiation is based on the Halsted model of disease pathogenesis, it is very different than en bloc surgical extirpation.”

Lumpectomy plus radiation is, indeed, different from a radical mastectomy! However, the statement that the former is based on the Halsted model of disease pathogenesis is incomprehensible.

  * “Detection by screening mammogram has allowed effective locoregional treatment before distant spread of sufficient number of cells capable of metastatic growth. In my judgment, this is strong argument against the systemic thesis.”

Several years before that statement was made, one of us (B.F.) asserted the following with regard to mammography:

“Current biological concepts indicate, however, that as a result of genetic alterations some occult tumors detected by mammography have populations of cells that have already attained competence for successfully establishing metastases; [others] have not yet achieved that capability but will do so as their cells continue to replicate, or will never demonstrate that capacity, even after they are detected by clinical examination. (A substantial proportion of patients with clinically detected cancers do not develop metastatic disease during their lifetime.)... the value or limitations of mammography relate not so much to the number of clinically occult tumors detected as to the biological nature of the cells in the tumors that are discovered. Perhaps… it will be possible to detect and remove more tumors whose cells have not yet undergone the biological changes required for them to attain the metastatic capability that would occur if the tumors were not recognized and not removed.”

Although the first sentence of his statement about screening mammography is correct, the reason that “this is a strong argument against the systemic thesis” is not clear.

  * “If differences [in outcome] are found, they must be due to differences in the persistence of disease in the primary tumor or nodal site resulting in differences in distant metastases.”

That differences in outcome must be due to differences in the persistence of disease is arguable. There are biologic explanations such as the heterogeneity of a tumor and of its host that are of equal or greater significance.

  * “Both the Halsted and the systemic hypotheses are too restricting.”

Hellman19 goes on to state that, “Like all dogma in science,... [those hypotheses] tend to limit our inquiries and deny the conditional and approximate nature of scientific knowledge.” This point of view is a philosophical one, rather than a scientific justification for condemning the alternative hypothesis.

In context with his criticism of our hypothesis, Hellman, in 1994, introduced a third hypothesis: one that “is most consistent with the data,” namely, the “spectrum” hypothesis. The statements presented in Table 3 are provided to compare the tenets of the “spectrum” thesis with those comprising the Halstedian and alternative hypotheses (Table 2).