This is the author’s final draft post-refereeing article published in

Breast Cancer Res Treat. 2009 Jul;116(2):329-38.

http://www.springerlink.com/content/957534h851427111/fulltext.pdf

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 Kjersti Tjensvoll1, Bjørnar Gilje2, Satu Oltedal1, Victor F. Shammas2, Jan Terje Kvaløy3, 4, Reino Heikkilä1, 2 and Oddmund Nordgård1, 3

1

Laboratory for Molecular Biology, Stavanger University Hospital, N-4016 Stavanger, Norway.

2

Department of Haematology and Oncology, Stavanger University Hospital, N-4068 Stavanger,

Norway. 3

Department of Mathematics and Natural Sciences, University of Stavanger, N-4036 Stavanger,

Norway 4

Division of Research and Human Resources, Stavanger University Hospital, N-4068 Stavanger,

Norway.

Correspondig author: Oddmund Nordgård Laboratory for Molecular Biology Stavanger University Hospital Torgveien 25B 1

N-4016 Stavanger Norway TEL: +47 47809092 E-mail: [email protected]

2

Abstract Purpose 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-specificand 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