Breast Cancer Outcomes and Micrometastatic Disease

Abstract

In Response: We appreciate the letter to the Editor by Drs. Harissis and Fatouros and agree in large part with their sentiment that new prognostic biomarkers both individually and in combination are likely the future of prognostication. Indeed, our own institution has pursued a variety of approaches including examining circulating tumor cells, circulating tumor DNA integrity, and proteomics. Currently, however, with the increased use of sentinel node biopsy, the diagnosis of micrometastasis is increasing. With so many conflicting reports as to the significance of these micrometastases, we have attempted to add some information that we hope will be helpful to clinicians in counseling patients as to their likely breast cancer outcomes. Because of the limitations of using the Surveillance Epidemiology and End Results (SEER) registry to determine the nonsurgical treatment of patients and the techniques of nodal evaluation, we have been careful to not assume that our findings indicate that micrometastatic disease requires more aggressive therapy. Rather, we merely reported outcomes. We encourage those designing trials to consider including these patients but stratifying them into pre-planned analyses, or to consider direct comparisons to determine the best treatment of this subgroup. While the challenge in showing superiority or equivalence for small absolute differences is difficult, this is a challenge that is common in breast cancer studies. A number of trials for early breast cancer have expected absolute improvements in survival at the single-digit level for their tested interventions, and treatment decisions are made every day based on such small changes in absolute survival. We would hope that these efforts to further elucidate the impact of micrometastases would complement rather than replace biomarker research, as one could easily envision how such complementary concepts could be unified into analyses done on a single large accrued patient population.