Gene expression profiling of luminal B breast cancers reveals NHERF1 as a new marker of endocrine resistance.
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Gene expression profiling of luminal B breast cancers reveals NHERF1 as a new marker of endocrine resistance. / Karn, Thomas; Ruckhäberle, Eugen; Hanker, Lars; Müller, Volkmar; Schmidt, Marcus; Solbach, Christine; Gätje, Regine; Gehrmann, Mathias; Holtrich, Uwe; Kaufmann, Manfred; Rody, Achim.
in: BREAST CANCER RES TR, Jahrgang 130, Nr. 2, 2, 2011, S. 409-420.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Gene expression profiling of luminal B breast cancers reveals NHERF1 as a new marker of endocrine resistance.
AU - Karn, Thomas
AU - Ruckhäberle, Eugen
AU - Hanker, Lars
AU - Müller, Volkmar
AU - Schmidt, Marcus
AU - Solbach, Christine
AU - Gätje, Regine
AU - Gehrmann, Mathias
AU - Holtrich, Uwe
AU - Kaufmann, Manfred
AU - Rody, Achim
PY - 2011
Y1 - 2011
N2 - The luminal B subtype represents a group of high proliferating estrogen receptor positive breast cancers which are associated with a poor prognosis. Genes exclusively expressed in this subtype should help to better understand these tumors. In a finding cohort of 171 breast cancers luminal B specific genes were identified displaying strong expression in highly proliferating Ki-67 positive/ER positive tumors but no expression either in Ki-67 negative/ER positive or in Ki-67 positive/ER negative samples. The clinical relevance of the scaffold protein NHERF1 identified by this strategy was assessed in a total of 3,030 breast cancers. NHERF1 expression was associated with the luminal B subtype both in the finding and validation cohort. A positive correlation of NHERF1 expression with tumor size (P < 0.001), grade (P < 0.001), and HER2 status (P = 0.033) was observed. NHERF1 expression was associated with a worse survival in ER positive breast cancer (P < 0.001) and retained its prognostic value in multivariate analysis. For ER positive samples with low NHERF1 expression a benefit of endocrine therapy was detected (P = 0.007). In contrast no differences in disease free survival were found for high NHERF1 expressing breast cancers which were either treated with endocrine therapy or no systemic therapy. Our data indicate that NHERF1 expressing breast cancers seem to have a greater risk to develop resistance to endocrine therapy. However, based on previous findings of NHERF1 functioning in PI3K signalling from basic research, these tumors might be appropriate candidates for a targeted therapy of the PI3K/Akt pathway.
AB - The luminal B subtype represents a group of high proliferating estrogen receptor positive breast cancers which are associated with a poor prognosis. Genes exclusively expressed in this subtype should help to better understand these tumors. In a finding cohort of 171 breast cancers luminal B specific genes were identified displaying strong expression in highly proliferating Ki-67 positive/ER positive tumors but no expression either in Ki-67 negative/ER positive or in Ki-67 positive/ER negative samples. The clinical relevance of the scaffold protein NHERF1 identified by this strategy was assessed in a total of 3,030 breast cancers. NHERF1 expression was associated with the luminal B subtype both in the finding and validation cohort. A positive correlation of NHERF1 expression with tumor size (P < 0.001), grade (P < 0.001), and HER2 status (P = 0.033) was observed. NHERF1 expression was associated with a worse survival in ER positive breast cancer (P < 0.001) and retained its prognostic value in multivariate analysis. For ER positive samples with low NHERF1 expression a benefit of endocrine therapy was detected (P = 0.007). In contrast no differences in disease free survival were found for high NHERF1 expressing breast cancers which were either treated with endocrine therapy or no systemic therapy. Our data indicate that NHERF1 expressing breast cancers seem to have a greater risk to develop resistance to endocrine therapy. However, based on previous findings of NHERF1 functioning in PI3K signalling from basic research, these tumors might be appropriate candidates for a targeted therapy of the PI3K/Akt pathway.
KW - Humans
KW - Female
KW - Middle Aged
KW - Multivariate Analysis
KW - Prognosis
KW - Disease-Free Survival
KW - Proportional Hazards Models
KW - Multigene Family
KW - Gene Expression
KW - Oligonucleotide Array Sequence Analysis
KW - Genetic Association Studies
KW - Receptors, Estrogen/genetics/metabolism
KW - Gene Expression Profiling
KW - Tumor Markers, Biological/genetics/metabolism
KW - Drug Resistance, Neoplasm
KW - Antineoplastic Agents, Hormonal/pharmacology
KW - Breast Neoplasms/diagnosis/genetics/pathology
KW - Carcinoma, Ductal, Breast/diagnosis/genetics/pathology
KW - Phosphoproteins/genetics/metabolism
KW - Sodium-Hydrogen Antiporter/genetics/metabolism
KW - Humans
KW - Female
KW - Middle Aged
KW - Multivariate Analysis
KW - Prognosis
KW - Disease-Free Survival
KW - Proportional Hazards Models
KW - Multigene Family
KW - Gene Expression
KW - Oligonucleotide Array Sequence Analysis
KW - Genetic Association Studies
KW - Receptors, Estrogen/genetics/metabolism
KW - Gene Expression Profiling
KW - Tumor Markers, Biological/genetics/metabolism
KW - Drug Resistance, Neoplasm
KW - Antineoplastic Agents, Hormonal/pharmacology
KW - Breast Neoplasms/diagnosis/genetics/pathology
KW - Carcinoma, Ductal, Breast/diagnosis/genetics/pathology
KW - Phosphoproteins/genetics/metabolism
KW - Sodium-Hydrogen Antiporter/genetics/metabolism
M3 - SCORING: Journal article
VL - 130
SP - 409
EP - 420
JO - BREAST CANCER RES TR
JF - BREAST CANCER RES TR
SN - 0167-6806
IS - 2
M1 - 2
ER -
