Abstract
BackgroundOperable breast cancer patients may experience late recurrences because of reactivation of dormant tumor cells within the bone marrow (BM). Identification of patients who would benefit from extended therapy is therefore needed.MethodsBM samples obtained pre- and post-surgery were previously analysed for presence of disseminated tumor cells (DTC) by a multimarker mRNA quantitative reverse-transcription PCR assay. Updated survival analyses were performed on all patient data (n = 191) and in a subgroup of patients alive and recurrence-free after 5 years (n = 156). DTC data were compared to the mitotic activity index (MAI) of the primary tumors. Median follow-up time was 15.3 years.ResultsAmong the 191 patients, 49 (25.65%) experienced systemic relapse, 24 (49%) within 5–18 years after surgery. MAI and pre- and post-operative DTC status had significant prognostic value based on Kaplan–Meier analyses and multiple Cox regression in the overall patient cohort. With exclusion of patients who relapsed or died within 5 years from surgery, only pre-operative DTC detection was an independent prognostic marker of late recurrences. High MAI (≥10) did not predict late recurrences or disease-specific mortality.ConclusionPre-operative DTC detection, but not MAI status, predicts late recurrences in operable breast cancer.
Highlights
Operable breast cancer patients may experience late recurrences because of reactivation of dormant tumor cells within the bone marrow (BM)
We evaluated the capacity of disseminated tumor cells (DTC) detection prior to and after surgery to predict long-term outcome in 191 operable, prospectively recruited breast cancer patients in comparison to other well-established prognostic markers such as mitotic activity index (MAI) and lymph node status in a retrospective analysis [14,15,16]
Neither post-operative DTC status nor MAI status was a Discussion We and others have previously shown that detection of DTCs in BM samples from operable breast cancer patients is associated with adverse clinical outcomes [14
Summary
Operable breast cancer patients may experience late recurrences because of reactivation of dormant tumor cells within the bone marrow (BM). Minimal residual disease is caused by spread of invasive tumor cells from the primary tumor through the circulation to distant sites [2, 3]. Tumor cells often migrate to the bone marrow (BM) where these disseminated tumor cells (DTCs) can survive for years by entering a dormant state. This is a prolonged quiescent state, in which tumor cells are present, but disease progression is not clinically manifested.
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