Persistent tumor cells in bone marrow of non-metastatic breast cancer patients after primary surgery are associated with inferior outcome.
BACKGROUND
To investigate the prognostic significance of disseminated tumor cells (DTCs) in bone marrow (BM) from non-metastatic breast cancer patients before and after surgery.


METHODS
Patients 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.


RESULTS
DTCs 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).


CONCLUSIONS
Detection 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.
Department of Haematology and Oncology, Stavanger University Hospital, N-4068, Stavanger, Norway.
Kjersti
K
Tjensvoll
Satu
S
Oltedal
Reino
R
Heikkilä
Jan Terje
JT
Kvaløy
Bjørnar
B
Gilje
James M
JM
Reuben
Rune
R
Smaaland
Oddmund
O
Nordgård
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D001853:Bone Marrow / Q000473:pathology*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000601:surgery; D005260:Female; D006801:Humans; D053539:Keratin-19 / Q000235:genetics; D060785:Mammaglobin A / Q000235:genetics; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics; D011379:Prognosis; D013997:Time Factors; D051879:Twist-Related Protein 1 / Q000235:genetics
D014408:Biomarkers, Tumor; D053539:Keratin-19; D060785:Mammaglobin A; D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1