Long-term follow-up of the randomized Stockholm trial on adjuvant tamoxifen among postmenopausal patients with early stage breast cancer

and prediction of response to adjuvant tamoxifen treatment in postmenopausal women with early stage invasive breast cancer. Patients and methodsThe Stockholm Breast Cancer Study Group conducted a randomized trial during 1976 through 1990 comparing adjuvant tamoxifen versus control. The patients were stratified according to tumor size and lymph node status in high risk and low risk groups. In this study we evaluated 683 patients with "low risk" breast cancer (size≤30 mm, lymph node-negative) for whom ER status had been determined by both the cytosol assays and immunohistochemistry at one pathology laboratory. The median follow up was 17 years. ResultSix hundred eighty three patients had tumors with ER determined by both methods, 536 (78.5%) were ERpositive by cytosol assays using the cut off level at ≥ 0.05 fmol/µg DNA and 539 patients were ER-positive ConclusionBoth IHC and cytosol assay accurately predict long-term response to adjuvant tamoxifen.3

Section: Discussionmentioning

confidence: 99%

Immunohistochemistry compared to cytosol assays for determination of estrogen receptor and prediction of the long-term effect of adjuvant tamoxifen

Khoshnoud

Löfdahl

Fohlin

et al. 2010

“…Most of the patients in the tamoxifen arm, if diseasefree after two years, were then randomised to receive tamoxifen for three more years, or no further adjuvant treatment. Detailed information about study design and long-term follow-up data have been previously reported in detail [9,10]. Median follow-up time was 11 years.…”

Section: Patientsmentioning

confidence: 99%

“…ER expression was determined at the time of diagnosis, before 1988 this was done using isoelectric focusing and after this year, quantitative enzyme immunoassay (EIA) was used [9,10]. Cut-off level for ER positivity was 0.05 fmol/μg DNA.…”

Section: Evaluation Of Er Her2 Pik3ca and Paktmentioning

confidence: 99%

Loss of protein tyrosine phosphatase, non-receptor type 2 is associated with activation of AKT and tamoxifen resistance in breast cancer

Karlsson

Veenstra

Emin

et al. 2015

Gene copy loss of PTPN2 was detected in 16% (34/215) of the tumours and this was significantly correlated with lower levels of PTPN2 mRNA. PTPN2 gene loss and lower mRNA levels were associated with activation of AKT and a poor prognosis. Furthermore, PTPN2 gene loss was a significant predictive marker of poor benefit from tamoxifen treatment.In conclusion, genomic loss of PTPN2 may be a previously unknown mechanism of PI3K/AKT upregulation in breast cancer. PTPN2 status is a potential new clinical marker of endocrine treatment benefit which could guide further individualised therapies in breast cancer.

“…The patient materials used to study S6K1/S6K2 gene amplification and S6K2 protein expression were previously reported in detail [28,29]. Briefly, accrual of high-risk and lowrisk postmenopausal patients started in November 1976 and ended in April 1990.…”

Section: Patientsmentioning

confidence: 99%

Clinical potential of the mTOR targets S6K1 and S6K2 in breast cancer

Pérez-Tenorio

Karlsson

Waltersson

et al. 2010

Aim: The Mammalian Target of Rapamycin (mTOR) and its substrates S6K1 and S6K2 regulate cell growth, proliferation and metabolism through translational control. RPS6KB1 (S6K1) and RPS6KB2 (S6K2) are situated in the commonly amplified 17q21-23 and 11q13regions. S6K1 amplification and protein overexpression have earlier been associated with a worse outcome in breast cancer, but information regarding S6K2 is scarce. The aim of this study was to evaluate the prognostic and treatment predictive relevance of S6K1/S6K2 gene amplification, as well as S6K2 protein expression in breast cancer. Results: S6K1 amplification/gain was detected in 10.7%/21.4% and S6K2 amplification/gain in 4.3%/21.3% of the tumors. S6K2 protein was detected in the nucleus (38%) and cytoplasm (76%) of the tumor cells. S6K1 amplification was significantly associated with HER2 gene amplification and protein expression. S6K2 amplification correlated significantly with high S6K2 mRNA levels, ER+ status and CCND1 amplification. S6K1 and S6K2 gene amplification was associated with a worse prognosis independent of HER2 and CCND1. S6K2 gain and nuclear S6K2 expression was related to an improved benefit from tamoxifen among patients with ER+ respectively ER+/PgR+ tumors. In the ER+/PgR-subgroup, nuclear S6K2 rather indicated decreased tamoxifen responsiveness. S6K1 amplification predicted reduced benefit from radiotherapy.Conclusions: This is the first study showing that S6K2 amplification and overexpression, like S6K1 amplification, have prognostic and treatment predictive significance in breast cancer.