Persistent tumor cells in bone marrow of non-metastatic breast cancer patients after primary surgery are associated with inferior outcomeReportar como inadecuado

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BMC Cancer

, 12:190

Translational oncology


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.

KeywordsBreast cancer Minimal residual disease Multimarker real-time PCR Bone marrow DTC prognosis Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-12-190 contains supplementary material, which is available to authorized users.

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Autor: Kjersti Tjensvoll - Satu Oltedal - Reino Heikkilä - Jan Terje Kvaløy - Bjørnar Gilje - James M Reuben - Rune Smaaland


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