The Heisenberg Uncertainty Principle Applied To Breast Cancer

Heisenberg postulated that the position and momentum of a particle could not be simultaneously known. His principle led to clearer understanding of the uncertainty inherent in scientific measurement. A similar paradox exists in assessing lymph node metastases with respect to knowing where they are but not knowing where they may have been going. Even if we could assess the biological potential of a single cell, cell cluster, or micrometastasis in a sentinel node, the node has already been removed from the patient: anything removed has no capacity to harm; only disease left behind has lethal potential. By assessing the disease removed from a patient, we infer from observational experience the risk of recurrence. Implicit in any risk prediction is the assumption and probability that some quantity of tumor with proliferative capacity remains in the patient. The failure pattern, or metastatic profile, for breast cancer has not changed over the course of our transition from radical mastectomy to conservative surgical management with adjuvant radiation and multidrug combination chemotherapy. Breast cancer progenitor cells in the bone marrow, liver, brain, or other safe harbor must escape eradication during treatment and survive to proliferate and secondarily disseminate. Any prognostic value for micrometastases or minute tumor cell clusters in sentinel nodes can only be assessed by correlating the multitude of measurable factors available for both the primary tumor and nodal tumor deposits with subsequent failure patterns then determining which factors are most predictive. Imprecision in risk estimates is guaranteed because the natural history of even an aggressive tumor may be altered if detected and treated early. However, failure to eradicate even one systemic progenitor cell carries a risk of recurrence. An aggressive systemic recurrence is, for most patients, incurable and something to be avoided if possible. This fear can drive us away from the rational consideration of risk versus benefit. The question in sentinel node biopsy is whether the enhanced detection of micrometastases is "the prognostic factor" that predicts systemic recurrence. This is too high an expectation. Early data on bone marrow micrometastases suggest that a more direct measurement of occult systemic disease has greater prognostic value than occult disease in sentinel nodes (8). Overly optimistic estimates of the prognostic value for micrometastases in sentinel nodes will subject too many patients to over-treatment.

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