Abstract
BackgroundTo investigate the prognostic significance of disseminated tumor cells (DTCs) in bone marrow (BM) from non-metastatic breast cancer patients before and after surgery.MethodsPatients with non-metastatic breast cancer were consecutively recruited to this project during the years 1998–2000. Real-time RT-PCR quantification of a DTC multimarker panel consisting of cytokeratin 19, mammaglobin A and TWIST1 mRNA was performed in BM samples obtained from 154 patients three weeks (BM2) and/or six months after surgery (BM3). The results were compared to previously published data from pre-operative BM analyses for the same patients.ResultsDTCs were identified in post-operative BM samples (BM2 and/or BM3) from 23 (15%) of the 154 patients investigated. During a median follow-up of 98 months, 10 (44%) of these patients experienced systemic relapse as compared to 16 (12%) of 131 DTC-negative patients. Kaplan-Meier estimates of systemic recurrence-free- and breast-cancer specific survival demonstrated significantly shorter survival for patients with persistent DTCs in BM after surgery (p≤0.001). By multivariate Cox regression analyses, persistent DTCs after surgery was an independent predictor of both systemic recurrence-free- (HR = 5.4, p < 0.001) and breast-cancer specific survival (HR = 5.3, p < 0.001). Furthermore, the prognostic value of DTCs in BM was similar for pre- and post surgery samples. However, patients with DTCs both before and after surgery (BM1 and BM2/3) had a particularly poor prognosis (systemic recurrence-free survival: HR = 7.2, p < 0.0001 and breast-cancer specific survival: HR = 8.0, p < 0.0001).ConclusionsDetection of persistent DTCs in BM samples obtained after surgery identified non-metastatic breast cancer patients at high risk for systemic relapse, and with reduced breast-cancer specific survival. Furthermore, patients with positive DTC status both before and after surgery had a particularly poor prognosis.
Highlights
To investigate the prognostic significance of disseminated tumor cells (DTCs) in bone marrow (BM) from non-metastatic breast cancer patients before and after surgery
Having 98 months (>8 years) median follow-up data for the patients, we have evaluated the prognostic significance of persistent DTCs in BM after surgery, and compared the prognostic and predictive information associated with the different sampling time points
Detection of persistent DTCs in BM samples obtained after primary surgery We have previously demonstrated by a MM quantitative RT-PCR panel that detection of DTCs in pre-operative BM samples (BM1) predicts clinical outcome in nonmetastatic breast cancer patients [16]
Summary
To investigate the prognostic significance of disseminated tumor cells (DTCs) in bone marrow (BM) from non-metastatic breast cancer patients before and after surgery. There is considerable evidence that detection of disseminated tumor cells (DTCs) in pre-operative bone marrow (BM) samples from non-metastatic breast cancer patients identifies a patient population at high risk for disease recurrence [1,2,3,4,5]. DTCs have been found in the BM after surgery, both before and after adjuvant cause resistance to conventional chemotherapeutic drugs [15] Both a prognostic and a predictive value of BM DTC detection after surgery seem likely. They observed a survival difference according to DTC status both before and after chemotherapy, the difference between the DTC positive and negative groups was statistically significant only for the BM samples obtained before chemotherapy [10]
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