Molecular detection of disseminated breast cancer cells in the bone marrow of early breast cancer patients using quantitative RT PCR for CEA.
Carcinoembryonic antigen (CEA) is widely used as a serum tumor marker in various types of cancer. Several systems for the CEA-RT-PCR approach have been reported to date. In this study, we have evaluated the quantitative CEA-RT-PCR as a diagnostic tool for detection of isolated tumor cells in bone marrow of early breast cancer patients prior to the administration of any adjuvant systemic therapy. We obtained bone marrow aspirates of 70 patients with stage I (37%), II (60%), and III (3%) breast cancer who underwent either immediate complete resection of the tumor or neoadjuvant therapy with subsequent curative surgery. mRNA was isolated using QIAamp RNA blood mini kit (Qiagen). Subsequently quantitative RT-PCR for the expression of CEA has been performed. CEA transcripts were detected in samples from 29 (41%) out of 70 patients. With a median follow-up of 22 months we observed 8 disease free survival (DFS) events including 4 systemic recurrences, 1 ductal in-situ carcinoma (DCIS), 1 local recurrence, and 2 deaths without tumour. Four DFS events (2 systemic recurrences, 2 deaths without tumor) occurred in patients with CEA transcripts in the bone marrow and 4 (2 systemic recurrences, 1 DCIS, 1 locoregional recurrence) in patients without CEA in the bone marrow. There was a trend to shorter DFS in the group with CEA in the bone marrow (p=0.05548). Overall survival was not assessed because only 2 deaths (both in patients without tumor) have been reported to date. Quantitative RT-PCR assay for CEA may be a useful tool for detection of occult breast cancer cells in the bone marrow. Clinical and prognostic relevance of minimal residual disease using this technique remains unproven. Our results should be interpreted with caution with regard to 2 deaths in CEA positive group with no relationship to disease recurrence.
Janku
F
F
Department of Oncology, First Faculty of Medicine, General Teaching Hospital, Charles University, Prague, Czech Republic. fjanku@bonsecours.ie
Srovnal
J
J
Korinkova
G
G
Novotny
J
J
Petruzelka
L
L
Power
D
D
Matous
B
B
Hajduch
M
M
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D019046:Bone Marrow Neoplasms / Q000175:diagnosis* / Q000556:secondary*; D001943:Breast Neoplasms / Q000473:pathology* / Q000628:therapy; D002272:Carcinoembryonic Antigen / Q000032:analysis*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods*
D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen