F1-1Predictive gene expression profile of breast cancer patients treated with tamoxifen

Tamoxifen (TAM) is effective in estrogen receptor positive (ER+) patients, reducing the risk of recurrence and death in all age groups. However, 25% of ER+/progesterone receptor positive (PR+) and 66% of ER+/PR- tumors do not respond to TAM, emphasizing the need for additional predictive markers. Th...

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Published in:APMIS : acta pathologica, microbiologica et immunologica Scandinavica microbiologica et immunologica Scandinavica, 2008, Vol.116 (3), p.223-252
Main Authors: Lyng, M.B, Kristensen, M.H, Aaberg-Jessen, C, Toft, B.G, Vyberg, Mogens, Lænkholm, Anne-Vibeke, Riber-Hansen, R, Sjö, L.D, Gjerdrum, Lise Mette, Ingemann-Hansen, O, Schledermann, Doris Ejersbo, Toxværd, Anders, Detlefsen, Sönke, Marquard, Lena, Skovby, Birthe Dyveke Marcussen, Mohammadi, Mahin, Engel, Ulla, Munkholm, Julie, Warnecke, Mads, Smith, Mads Bo, Klarskov, Louise, Willemoe, Gro Linno, Barstad, Bente, Larsen, Lise Grupe, Lund, Helle, Hariri, Jalil, Nedergaard, Bettina S, Waldstrøm, M, Winther, C, Ehlers, Charlotte Cort, Jensen, Trine O, Pilt, Anette Pedersen, Hasselby, Jane Preuss, Andersen, Luise, Thomsen, Jørgen L, Belge, Gazanfer, Clasen-Linde, Erik, Brügmann, Anja, Roslind, A, Ekvall Filtenborg-Barnkob, Bettina, Lund, Eva Løbner, Rasmussen, Birgitte B, Pernille Vahl, Jacobsen, Katrine, Pedersen, Marianne, Tramm, T, Rasmussen, B.B, Foged, Niels T
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Language:English
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Summary:Tamoxifen (TAM) is effective in estrogen receptor positive (ER+) patients, reducing the risk of recurrence and death in all age groups. However, 25% of ER+/progesterone receptor positive (PR+) and 66% of ER+/PR- tumors do not respond to TAM, emphasizing the need for additional predictive markers. The aim of this study was to develop a predictive gene expression profile for TAM response in high-risk, lymph node positive (N+) patients employing technique directly transferable to a routine molecular diagnostic laboratory. Thirty patients with recurrent disease (average time to relaps 2.96 years) were matched to 30 patients without recurrence. All patients were high-risk ER+ patients, paired according to lymph node status (N), malignancy grade, tumor size, WHO diagnosis and duration of TAM treatment. All patients were post-menopausal and all but one pair had a N+ status at time of diagnosis. All patients were treated with TAM as monotherapy for an average of 1.8 years. The average follow-up time was 13.7 years (range: 7.2-17.8). Total RNA was purified from primary frozen tumors and the gene expression of 59 endocrine treatment-related target genes were investigated. The target genes were normalized to 4 averaged reference genes, previously identified to be optimal for studying ER+ breast cancer samples. The gene expression was investigated by a novel qRT-PCR technique termed Low Density Arrays. Using a paired Wilcoxon rank sum test, we found more genes with low p-values than one can expect under chance conditions. Using a permutation test to adjust for multiple testing, two genes showed a significant difference at the 5% level. Among the 18 genes with p
ISSN:0903-4641
1600-0463