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dc.contributor.authorKhoshnoud, M R
dc.contributor.authorLöfdahl, B
dc.contributor.authorFohlin, H
dc.contributor.authorFornander, T
dc.contributor.authorStål, O
dc.contributor.authorSkoog, L
dc.contributor.authorBergh, Jonas
dc.contributor.authorNordenskjöld, B
dc.date.accessioned2012-01-04T11:56:21Z
dc.date.available2012-01-04T11:56:21Z
dc.date.issued2011-04
dc.identifier.citationImmunohistochemistry compared to cytosol assays for determination of estrogen receptor and prediction of the long-term effect of adjuvant tamoxifen. 2011, 126 (2):421-30 Breast Cancer Res. Treat.en
dc.identifier.issn1573-7217
dc.identifier.pmid20957430
dc.identifier.doi10.1007/s10549-010-1202-7
dc.identifier.urihttp://hdl.handle.net/10541/199971
dc.description.abstractThe purpose of this study is to compare immunohistochemistry (IHC) and cytosol-based assays for determination of estrogen receptor (ER) and prediction of response to adjuvant tamoxifen treatment in postmenopausal women with early-stage invasive breast cancer. The 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 IHC at one pathology laboratory. The median follow-up was 17 years. Six hundred eighty-three patients had tumors with ER determined by both methods, 536 (78.5%) were ER-positive by cytosol assays using the cutoff level at ≥0.05 fmol/μg DNA and 539 patients were ER-positive (79%) by IHC using the cutoff level at ≥10% cell stained. Thirty-nine tumors (5.7%) were ER-positive by cytosol but not by IHC, whereas the opposite pattern was found for 42 cases (6.1%). Only seven tumors had stained cells between 0 and 9% by IHC. The concordance between IHC and cytosol assays was high (88%). The kappa statistic was 0.65, 95% CI 0.58-0.72. Among patients classified as ER-negative no therapeutic benefit from tamoxifen was observed. Among patients with ER-expressing tumors, tamoxifen resulted in significantly better recurrence-free survival irrespective of the method (IHC: HR, 0.53, P < 0.001; cytosol: HR, 0.53, P < 0.001). The effect on overall survival was not statistically significant probably due to the limited sample size. Both IHC and cytosol assay accurately predict long-term response to adjuvant tamoxifen.
dc.language.isoenen
dc.subject.meshAdult
dc.subject.meshAged
dc.subject.meshAntineoplastic Agents, Hormonal
dc.subject.meshBreast Neoplasms
dc.subject.meshChemotherapy, Adjuvant
dc.subject.meshDisease-Free Survival
dc.subject.meshFemale
dc.subject.meshHumans
dc.subject.meshImmunohistochemistry
dc.subject.meshMiddle Aged
dc.subject.meshMolecular Diagnostic Techniques
dc.subject.meshROC Curve
dc.subject.meshReceptors, Estrogen
dc.subject.meshTamoxifen
dc.subject.meshTime Factors
dc.subject.meshTreatment Outcome
dc.titleImmunohistochemistry compared to cytosol assays for determination of estrogen receptor and prediction of the long-term effect of adjuvant tamoxifen.en
dc.typeArticleen
dc.contributor.departmentDepartment of Oncology, Karolinska University Hospital, Karolinska Institute, Södersjukhuset, 11883, Stockholm, Sweden.en
dc.identifier.journalBreast Cancer Research and Treatmenten
refterms.dateFOA2020-04-27T12:54:47Z
html.description.abstractThe purpose of this study is to compare immunohistochemistry (IHC) and cytosol-based assays for determination of estrogen receptor (ER) and prediction of response to adjuvant tamoxifen treatment in postmenopausal women with early-stage invasive breast cancer. The 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 IHC at one pathology laboratory. The median follow-up was 17 years. Six hundred eighty-three patients had tumors with ER determined by both methods, 536 (78.5%) were ER-positive by cytosol assays using the cutoff level at ≥0.05 fmol/μg DNA and 539 patients were ER-positive (79%) by IHC using the cutoff level at ≥10% cell stained. Thirty-nine tumors (5.7%) were ER-positive by cytosol but not by IHC, whereas the opposite pattern was found for 42 cases (6.1%). Only seven tumors had stained cells between 0 and 9% by IHC. The concordance between IHC and cytosol assays was high (88%). The kappa statistic was 0.65, 95% CI 0.58-0.72. Among patients classified as ER-negative no therapeutic benefit from tamoxifen was observed. Among patients with ER-expressing tumors, tamoxifen resulted in significantly better recurrence-free survival irrespective of the method (IHC: HR, 0.53, P < 0.001; cytosol: HR, 0.53, P < 0.001). The effect on overall survival was not statistically significant probably due to the limited sample size. Both IHC and cytosol assay accurately predict long-term response to adjuvant tamoxifen.


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