Phosphorylation of estrogen receptor α serine 167 is predictive of response to endocrine therapy and increases postrelapse survival in metastatic breast cancer

INTRODUCTION: Endocrine therapy is the most important treatment option for women with hormone-receptor-positive breast cancer. The potential mechanisms for endocrine resistance involve estrogen receptor (ER)-coregulatory proteins and crosstalk between ER and other growth factor signaling networks. However, the factors and pathways responsible for endocrine resistance are still poorly identified. METHODS: Using immunohistochemical techniques, we focused on the expression and phosphorylation of hormone receptors themselves and examined the phosphorylation of ER-α Ser118 and ER-α Ser167 and the expression of ER-α, ER-β1, ER-βcx/β2, progesterone receptor (PR), PRA, and PRB in the primary breast carcinomas of 75 patients with metastatic breast cancer who received first-line treatment with endocrine therapy after relapse. RESULTS: Phosphorylation of ER-α Ser118, but not Ser167, was positively associated with overexpression of HER2, and HER2-positive tumors showed resistance to endocrine therapy. The present study has shown for the first time that phosphorylation of ER-α Ser167, but not Ser118, and expression of PRA and PRB, as well as ER-α and PR in primary breast tumors are predictive of response to endocrine therapy, whereas expression of ER-β1 and ER-βcx/β2 did not affect response to the therapy. In addition, patients with either high phosphorylation of ER-α Ser167, or high expression of ER-α, PR, PRA, or PRB had a significantly longer survival after relapse. CONCLUSION: These data suggest that phosphorylation of ER-α Ser167 is helpful in selecting patients who may benefit from endocrine therapy and is a prognostic marker in metastatic breast cancer

Quantitative Assessment of Intervertebral Disc Composition by MRI: Sensitivity to Diurnal Variation

Whether diurnal variation exists in quantitative MRI indices such as the T1rho relaxation time (T1ρ) of the intervertebral disc (IVD) is yet to be explored. This prospective study aimed to evaluate the diurnal variation in T1ρ, apparent diffusion coefficient (ADC), and electrical conductivity (σ) of lumbar IVD and its relationship with other MRI or clinical indices. Lumbar spine MRI, including T1ρ imaging, diffusion-weighted imaging (DWI), and electric properties tomography (EPT), was conducted on 17 sedentary workers twice (morning and evening) on the same day. The T1ρ, ADC, and σ of IVD were compared between the time points. Their diurnal variation, if any, was tested for correlation with age, body mass index (BMI), IVD level, Pfirrmann grade, scan interval, and diurnal variation in IVD height index. The results showed a significant decrease in T1ρ and ADC and a significant increase in the σ of IVD in the evening. T1ρ variation had a weak correlation with age and scan interval, and ADC variation with scan interval. Diurnal variation exists for the T1ρ, ADC, and σ of lumbar IVD, which should be accounted for in image interpretation. This variation is thought to be due to diurnal variations in intradiscal water, proteoglycan, and sodium ion concentration

The effect of adjuvant systemic therapy on prognostic impact of polymorphisms

<p><b>Copyright information:</b></p><p>Taken from "Association of codon 72 polymorphism and the outcome of adjuvant therapy in breast cancer patients"</p><p>http://breast-cancer-research.com/content/9/3/R34</p><p>Breast Cancer Research 2007;9(3):R34-R34.</p><p>Published online 30 May 2007</p><p>PMCID:PMC1929098.</p><p></p> codon 72 and adjuvant chemotherapy alone (= 137); codon 72 and adjuvant chemotherapy with or without hormonal therapy (= 281); codon 72 and adjuvant hormonal therapy alone (= 195); codon 72 and no adjuvant systemic therapy (= 77); SNP309 and adjuvant tamoxifen with or without luteinizing hormone-releasing hormone analog (= 185). DFS, disease-free survival

Immunoblot analysis of phosphorylated estrogen receptor (ER)-α Ser118 and ER-α Ser167

<p><b>Copyright information:</b></p><p>Taken from "Phosphorylation of estrogen receptor α serine 167 is predictive of response to endocrine therapy and increases postrelapse survival in metastatic breast cancer"</p><p>Breast Cancer Research 2005;7(5):R753-R764.</p><p>Published online 27 Jul 2005</p><p>PMCID:PMC1242143.</p><p>Copyright © 2005 Yamashita et al.; licensee BioMed Central Ltd.</p> Transfected COS-7 cells were grown in serum- and estrogen-deprived conditions and treated with vehicle (medium) (lane 1), 17β-estradiol (E) (lane 2), epidermal growth factor (EGF) (lane 3), or Eand EGF (lane 4) for 30 min. Equal amounts of total protein from whole cell lysates were blotted for either anti-ER-α-phosphoserine (α-pS118 and α-pS167) and anti-ER-α (α-ER-α) antibodies. T47D cells were grown in serum- and estrogen-deprived conditions and treated with vehicle (medium) (lane 1), 17β-estradiol (E) for 10 min (lane 2) and 30 min (lane 3), EGF for 10 min (lane 4) and 30 min (lane 5), or Eand EGF for 10 min (lane 6) and 30 min (lane 7). Equal amounts of total protein from whole cell lysates were blotted for either anti-ER-α-phosphoserine (α-pS118 and α-pS167) and anti-ER-α (α-ER-α) antibodies

Representative immunohistochemical staining of estrogen receptor (ER)-α Ser118, and ER-α Ser167 in normal breast epithelium and invasive ductal carcinoma

<p><b>Copyright information:</b></p><p>Taken from "Phosphorylation of estrogen receptor α serine 167 is predictive of response to endocrine therapy and increases postrelapse survival in metastatic breast cancer"</p><p>Breast Cancer Research 2005;7(5):R753-R764.</p><p>Published online 27 Jul 2005</p><p>PMCID:PMC1242143.</p><p>Copyright © 2005 Yamashita et al.; licensee BioMed Central Ltd.</p> Phosphorylation of ER-α Ser118 in normal breast epithelium and invasive ductal carcinoma: negative (b) and positive (c) nuclear staining was observed in carcinoma cells. Phosphorylation of ER-α Ser167 in normal breast epithelium and invasive ductal carcinoma: negative (e) and positive (f) nuclear staining was observed in carcinoma cells (magnification, 400×)