Table 3. The Spectrum Hypothesis (1994)
A third hypothesis [the spectrum thesis] considers breast cancer to be a heterogeneous disease that can be thought of as a spectrum of proclivities [tendencies] extending from a disease that remains local throughout its course to one that is systemic when first detectable.

This hypothesis suggests that metastases are a function of tumor growth and progression.

Lymph node involvement is of prognostic importance not only because it indicates a more malignant tumor biology, but also because persistent disease in the lymph nodes can be the source of distant disease.

This model requires that there are meaningful clinical situations in which lymph nodes are involved, but there has not yet been any distant disease.

Persistent disease, locally or regionally, may give rise to distant metastases and, therefore, in contrast to the systemic theory, locoregional therapy is important.

This third, or spectrum, theory suggests that even if, as the systemic theory suggests, tumor cells spread distantly early in the natural history of the disease, metastases do not regularly occur.

A most important parameter determining the likelihood of their presentation [metastases] is tumor size.

Therefore, there are significant times in the clinically relevant natural history of the disease when metastases have not occurred, but, if the tumor is left inadequately treated, metastases will occur.

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Hellman’s idea that breast cancer is a heterogeneous disease and that metastases are a function of tumor growth and progression was hardly new when he considered it worthy of being a tenet of his “new” hypothesis. Almost 15 years before the formulation of his thesis, I (B.F.) stated that “... the term breast cancer is an eponym used to describe a biologically heterogeneous group of cancers of the breast residing in a biologically heterogeneous group of women. The varied ‘natural history’ following treatment by operation and no other therapy is an indicator of that host-tumor heterogeneity.” I also affirmed that “Tumors possess differing histopathological characteristics which relate to patient outcome,” and that “... not only is there heterogeneity between tumors but also that individual tumors are comprised of a heterogeneous population of cells which express their differences in innumerable ways.” Hellman also ignored the statement that I (B.F.) made in 1980 that “... the profile of the disparate cells comprising a tumor is almost certainly continuously changing and [that] evaluation at one point in time [after tumor removal] may be akin to examining a single frame removed from a motion picture film.”

Hellman’s statement that his theory suggests that, even if tumor cells spread early, metastases do not regularly occur, is a replica of my statement in 1980 that, even though “... a tumor is a systemic disease. ... that premise never implied that all patients will develop overt metastases in their lifetime. Conversely, it does not imply that only those with metastases represent the population with disseminated disease.”

Hellman’s contention that a most important factor for determining the likelihood of metastasis is tumor size is “Halstedian” in concept and has been addressed in my (B.F.) 1970 monograph as follows:

“More than 2,000 patients entered into the National Surgical Adjuvant Breast Project were utilized to evaluate the validity of the concept that the size of breast neoplasms influences prognosis. It was concluded that size alone is not as consequential to the fate of the patient as are other factors relative to the tumor and/or host that determine the development of metastases. ... Since size (ie, growth) is now recognized to be dependent on such factors as the number of proliferating cells, the length of the cycle—which is not always uniform—the extent of cell death or cell loss and the number of nonproliferating cells,... it is difficult to relate size to the age of a tumor.”

I (B.F.) also noted that “a large tumor that had not metastasized prior to its removal may be considered early and a small one that had already disseminated may be considered late.”

Thus, unlike the tenets of the alternative hypothesis, which were based on laboratory and clinical investigation, the spectrum hypothesis consists of a heterogeneous collection of empirical thoughts and generalities (Table 3). That contention is supported by several statements that Hellman made in a subsequent publication. In that article he stated that, “A third paradigm [the spectrum thesis], one that synthesizes the contiguous-systemic dialectic [presumably the Halsted and Fisher hypotheses], has been suggested by one of us to explain the natural history of breast cancer. This thesis argues that cancer comprises a biologic spectrum extending from a disease that remains localized to one that is systemic when first detectable but with many intermediate states. Metastases are a function of both tumor size and tumor progression.”