TY - JOUR
T1 - Modulation of ER phosphorylation on serine 118 by endocrine therapy
T2 - A new surrogate marker for efficacy
AU - Zoubir, M.
AU - Mathieu, M. C.
AU - Mazouni, C.
AU - Liedtke, C.
AU - Corley, L.
AU - Geha, S.
AU - Bouaziz, J.
AU - Spielmann, M.
AU - Drusche, F.
AU - Symmans, W. F.
AU - Delaloge, S.
AU - Andre, Fabrice
PY - 2008/1/1
Y1 - 2008/1/1
N2 - Background: Phosphorylation of serine 118 (ser118) has been reported to be involved in the activation of estrogen receptor (ER). In the present study, we evaluated whether endocrine therapy modulated ER phosphorylation on ser118. Patients and methods: We carried out a tissue microarray that included 80 primary breast tumors obtained before the administration of endocrine therapy. A second tissue microarray included 52 tumors obtained after endocrine therapy from the same patients. Immunostainings were carried out for ER, Pser118ER, Her2, insulin growth factor receptor (IGFR), p21-activated kinase 1 (PAK1), pMAPK, bcl2 and progesterone receptor. Results: Pser118ER staining was higher in Her2- (P = 0.06), IGFR- (P = 0.0002) and pMAPK-expressing tumors (P = 0.001). The level of ER phosphorylation was not different according to the occurrence of clinical tumor response (P = 0.16). Pser118ER expression was significantly reduced by endocrine therapy. The mean Pser118ER score was 163 [standard deviation (SD) 81] before endocrine therapy and 80 (SD 90) after endocrine therapy (P = 0.0001, paired t-test). The magnitude of Pser118ER decrease was higher in tumors that responded to endocrine therapy (mean decrease 128, SD 86) as compared with refractory tumors (mean decrease 38, SD 130) (P = 0.017, t -test). Conclusion: These findings suggest that endocrine therapy modulates ER on ser118. Pser118ER immunostaining could be used as surrogate marker to monitor treatment efficacy.
AB - Background: Phosphorylation of serine 118 (ser118) has been reported to be involved in the activation of estrogen receptor (ER). In the present study, we evaluated whether endocrine therapy modulated ER phosphorylation on ser118. Patients and methods: We carried out a tissue microarray that included 80 primary breast tumors obtained before the administration of endocrine therapy. A second tissue microarray included 52 tumors obtained after endocrine therapy from the same patients. Immunostainings were carried out for ER, Pser118ER, Her2, insulin growth factor receptor (IGFR), p21-activated kinase 1 (PAK1), pMAPK, bcl2 and progesterone receptor. Results: Pser118ER staining was higher in Her2- (P = 0.06), IGFR- (P = 0.0002) and pMAPK-expressing tumors (P = 0.001). The level of ER phosphorylation was not different according to the occurrence of clinical tumor response (P = 0.16). Pser118ER expression was significantly reduced by endocrine therapy. The mean Pser118ER score was 163 [standard deviation (SD) 81] before endocrine therapy and 80 (SD 90) after endocrine therapy (P = 0.0001, paired t-test). The magnitude of Pser118ER decrease was higher in tumors that responded to endocrine therapy (mean decrease 128, SD 86) as compared with refractory tumors (mean decrease 38, SD 130) (P = 0.017, t -test). Conclusion: These findings suggest that endocrine therapy modulates ER on ser118. Pser118ER immunostaining could be used as surrogate marker to monitor treatment efficacy.
KW - Aromatase inhibitor
KW - Breast cancer
KW - Predictive biomarker
KW - Sstrogen receptor
KW - Tamoxifen
UR - http://www.scopus.com/inward/record.url?scp=48749094406&partnerID=8YFLogxK
U2 - 10.1093/annonc/mdn151
DO - 10.1093/annonc/mdn151
M3 - Article
C2 - 18436523
AN - SCOPUS:48749094406
SN - 0923-7534
VL - 19
SP - 1402
EP - 1406
JO - Annals of Oncology
JF - Annals of Oncology
IS - 8
ER -