A small subgroup of operable breast cancer patients with poor prognosis identified by quantitative real-time RT-PCR detection of mammaglobin A and trefoil factor 1 mRNA expression in bone marrow.
OBJECTIVE
The utility of three different epithelial mRNA markers to detect clinically significant, disseminated tumour cells in bone marrow (BM) was explored.


METHODS
Mammaglobin A (hMAM), trefoil factor 1 (TFF-1) and prostate derived Ets factor (PDEF) mRNA were quantitated by real-time RT-PCR in BM samples from 192 breast cancer patients undergoing surgery (control group: 26 healthy women).


RESULTS
During a median follow-up of 72 months, four of the five hMAM BM-positive and three of the seven TFF-1 BM-positive patients experienced a systemic relapse. Kaplan-Meier survival analyses demonstrated significantly shorter recurrence-free-, breast-cancer-specific- and overall survival for both hMAM and TFF-1 BM-positive patients. In contrast, PDEF mRNA quantitation did not reveal any significant differences in the survival analyses. Multivariate Cox regression demonstrated hMAM mRNA BM expression to be an independent predictor of both overall- (hazard ratio = 5.896), breast-cancer-specific- (hazard ratio = 10.208) and systemic-recurrence-free survival (hazard ratio = 14.304). TFF-1 status was related to hMAM status (P < 0.001).


CONCLUSIONS
Breast cancer patients with pre-operative elevated BM levels of hMAM and/or TFF-1 mRNA seem to constitute a small group of patients with a very poor prognosis.
Laboratory for Molecular Biology, Stavanger University Hospital, Stavanger, Norway.
Kjersti
K
Tjensvoll
Bjørnar
B
Gilje
Satu
S
Oltedal
Victor F
VF
Shammas
Jan Terje
JT
Kvaløy
Reino
R
Heikkilä
Oddmund
O
Nordgård
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D001853:Bone Marrow / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D060785:Mammaglobin A; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D011379:Prognosis; D050783:Proto-Oncogene Proteins c-ets / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics*; D014598:Uteroglobin / Q000096:biosynthesis / Q000235:genetics*
D014408:Biomarkers, Tumor; D060785:Mammaglobin A; D009363:Neoplasm Proteins; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger; C556448:SCGB2A2 protein, human; C403974:SPDEF protein, human; C051838:TFF1 protein, human; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins; D014598:Uteroglobin