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Emdin, Stefan
Publications (10 of 13) Show all publications
Wärnberg, F., Garmo, H., Emdin, S., Hedberg, V., Adwall, L., Sandelin, K., . . . Holmberg, L. (2014). Effect of radiotherapy after breast-conserving surgery for ductal carcinoma in situ: 20 years follow-up in the randomized SweDCIS trial. Journal of Clinical Oncology, 32(32), 3613-3618
Open this publication in new window or tab >>Effect of radiotherapy after breast-conserving surgery for ductal carcinoma in situ: 20 years follow-up in the randomized SweDCIS trial
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2014 (English)In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 32, no 32, p. 3613-3618Article in journal (Refereed) Published
Abstract [en]

PURPOSE: Four randomized studies show that adjuvant radiotherapy (RT) lowers the risk of subsequent ipsilateral breast events (IBEs) after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) by approximately 50% after 10 to 15 years. We present 20 years of follow-up data for the SweDCIS trial. PATIENTS AND METHODS: Between 1987 and 1999 1,046 women were randomly assigned to RT or not after BCS for primary DCIS. Results up to 2005 have been published, and we now add another 7 years of follow-up. All breast cancer events and causes of death were registered. RESULTS: There were 129 in situ and 129 invasive IBEs. Absolute risk reduction in the RT arm was 12.0% at 20 years (95% CI, 6.5 to 17.7), with a relative risk reduction of 37.5%. Absolute reduction was 10.0% (95% CI, 6.0 to 14.0) for in situ and 2.0% (95% CI, -3.0 to 7.0) for invasive IBEs. There was a nonstatistically significantly increased number of contralateral events in the RT arm (67 v 48 events; hazard ratio, 1.38; 95% CI, 0.95 to 2.00). Breast cancer-specific death and overall survival were not influenced. Younger women experienced a relatively higher risk of invasive IBE and lower effect of RT. The hazard over time looked different for in situ and invasive IBEs. CONCLUSION: Use of adjuvant RT is supported by 20-year follow-up. Modest protection against invasive recurrences and a possible increase in contralateral cancers still call for a need to find groups of patients for whom RT could be avoided or mastectomy with breast reconstruction is indicated.

Place, publisher, year, edition, pages
The American Society of Clinical Oncology, 2014
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-97218 (URN)10.1200/JCO.2014.56.2595 (DOI)000344860000010 ()25311220 (PubMedID)
Available from: 2014-12-18 Created: 2014-12-12 Last updated: 2018-06-07Bibliographically approved
Klintman, M., Nilsson, F., Bendahl, P.-O. -., Ferno, M., Liljegren, G., Emdin, S. & Malmstrom, P. (2013). A prospective, multicenter validation study of a prognostic index composed of S-phase fraction, progesterone receptor status, and tumour size predicts survival in node-negative breast cancer patients: NNBC, the node-negative breast cancer trial. Annals of Oncology, 24(9), 2284-2291
Open this publication in new window or tab >>A prospective, multicenter validation study of a prognostic index composed of S-phase fraction, progesterone receptor status, and tumour size predicts survival in node-negative breast cancer patients: NNBC, the node-negative breast cancer trial
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2013 (English)In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 24, no 9, p. 2284-2291Article in journal (Refereed) Published
Abstract [en]

In a retrospective study on node-negative breast cancer, a prognostic index consisting of a proliferation factor, S-phase fraction (SPF), progesterone receptor status (PR), and tumour size identified one-third of patients as high risk, with a sixfold increased risk of breast cancer death. This prospective multicenter cohort study was set up to validate the index. In 576 T1-2N0 patients < 60 years, prospective analyses of PR and SPF were carried out. High risk was defined as >= 2 of the following: size > 20 mm, PR-negativity, and high SPF (in the absence of SPF, Bloom-Richardson grade 3). Median follow-up was 17.8 years. Thirty-one percent were high risk. In univariate analysis, the index was prognostic for breast cancer-specific survival after 5 years [hazard ratio (HR) = 4.7, 95% confidence interval (95% CI) 2.5-8.9], 10 years (HR = 2.2, 95% CI 1.5-3.3), and 15 years (HR = 1.7, 95% CI 1.2-2.5), and remained significant after adjustment for adjuvant medical treatment and age. In the 37% of patients with no risk factors, only one patient died of breast cancer the first 5 years. This prospective study validates a prognostic index consisting of a proliferation factor, PR-status, and tumour size. The index may be helpful for prognostic considerations and for selection of patients in need of adjuvant therapy.

Keywords
breast cancer, prognosis, proliferation, prospective, S-phase, validation
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-81003 (URN)10.1093/annonc/mdt186 (DOI)000323963100012 ()
Available from: 2013-10-01 Created: 2013-09-30 Last updated: 2018-06-08Bibliographically approved
Holmberg, L., Wong, Y. N., Tabar, L., Ringberg, A., Karlsson, P., Arnesson, L.-G., . . . Emdin, S. (2013). Mammography casting-type calcification and risk of local recurrence in DCIS: analyses from a randomised study. British Journal of Cancer, 108(4), 812-819
Open this publication in new window or tab >>Mammography casting-type calcification and risk of local recurrence in DCIS: analyses from a randomised study
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2013 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 108, no 4, p. 812-819Article in journal (Refereed) Published
Abstract [en]

Background: We studied the association between mammographic calcifications and local recurrence in the ipsilateral breast. Methods: Case-cohort study within a randomised trial of radiotherapy in breast conservation for ductal cancer in situ of the breast (SweDCIS). We studied mammograms from cases with an ipsilateral breast event (IBE) and from a subcohort randomly sampled at baseline. Lesions were classified as a density without calcifications, architectural distortion, powdery, crushed stone-like or casting-type calcifications. Results: Calcifications representing necrosis were found predominantly in younger women. Women with crushed stone or casting-type microcalcifications had higher histopathological grade and more extensive disease. The relative risk (RR) of a new IBE comparing those with casting-type calcifications to those without calcifications was 2.10 (95% confidence interval (Cl) 0.92-4.80). This risk was confined to in situ recurrences; the RR of an IBE associated with casting-type calcifications on the mammogram adjusted for age and disease extent was 16.4 (95% Cl 2.20-140). Conclusion: Mammographic appearance of ductal carcinoma in situ of the breast is prognostic for the risk of an in situ IBE and may also be an indicator of responsiveness to RT in younger women.

Keywords
DCIS, ipsilateral recurrence, mammographic calcifications, radiotherapy, breast-conserving surgery, randomised trial
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-68911 (URN)10.1038/bjc.2013.26 (DOI)000316775900011 ()
Available from: 2013-05-06 Created: 2013-04-29 Last updated: 2018-06-08Bibliographically approved
Holmberg, L., Garmo, H., Granstrand, B., Ringberg, A., Arnesson, L.-G., Sandelin, K., . . . Emdin, S. (2008). Absolute risk reductions for local recurrence after postoperative radiotherapy after sector resection for ductal carcinoma in situ of the breast.. J Clin Oncol, 26(8), 1247-52
Open this publication in new window or tab >>Absolute risk reductions for local recurrence after postoperative radiotherapy after sector resection for ductal carcinoma in situ of the breast.
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2008 (English)In: J Clin Oncol, ISSN 1527-7755, Vol. 26, no 8, p. 1247-52Article in journal (Refereed) Published
Keywords
Aged, Breast Neoplasms/*radiotherapy/*surgery, Carcinoma; Ductal; Breast/radiotherapy/surgery, Carcinoma; Intraductal; Noninfiltrating/*radiotherapy/*surgery, Female, Humans, Middle Aged, Neoplasm Recurrence; Local/etiology/*prevention & control, Postoperative Period, Risk Reduction Behavior, Survival Rate, Sweden, Treatment Outcome
Identifiers
urn:nbn:se:umu:diva-11037 (URN)18250350 (PubMedID)
Available from: 2008-11-13 Created: 2008-11-13 Last updated: 2018-06-09Bibliographically approved
Ringberg, A., Nordgren, H., Thorstensson, S., Idvall, I., Garmo, H., Granstrand, B., . . . Holmberg, L. (2007). Histopathological risk factors for ipsilateral breast events after breast conserving treatment for ductal carcinoma in situ of the breast--results from the Swedish randomised trial.. Eur J Cancer, 43(2), 291-8
Open this publication in new window or tab >>Histopathological risk factors for ipsilateral breast events after breast conserving treatment for ductal carcinoma in situ of the breast--results from the Swedish randomised trial.
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2007 (English)In: Eur J Cancer, ISSN 0959-8049, Vol. 43, no 2, p. 291-8Article in journal (Refereed) Published
Keywords
Breast Neoplasms/*pathology/radiotherapy/surgery, Carcinoma; Ductal; Breast/*pathology/radiotherapy/surgery, Case-Control Studies, Cohort Studies, Female, Humans, Mastectomy; Segmental, Radiotherapy; Adjuvant, Risk Factors
Identifiers
urn:nbn:se:umu:diva-5972 (URN)17118648 (PubMedID)
Available from: 2008-10-08 Created: 2008-10-08 Last updated: 2018-06-09Bibliographically approved
Emdin, S., Granstrand, B., Ringberg, A., Sandelin, K., Arnesson, L.-G., Nordgren, H., . . . Wallgren, A. (2006). SweDCIS: Radiotherapy after sector resection for ductal carcinoma in situ of the breast. Results of a randomised trial in a population offered mammography screening.. Acta Oncol, 45(5), 536-43
Open this publication in new window or tab >>SweDCIS: Radiotherapy after sector resection for ductal carcinoma in situ of the breast. Results of a randomised trial in a population offered mammography screening.
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2006 (English)In: Acta Oncol, ISSN 0284-186X, Vol. 45, no 5, p. 536-43Article in journal (Refereed) Published
Keywords
Breast Neoplasms/diagnosis/radiotherapy/surgery, Carcinoma in Situ/diagnosis/radiotherapy/surgery, Disease-Free Survival, Female, Follow-Up Studies, Humans, Mammography/*methods, Mass Screening/*methods, Middle Aged, Predictive Value of Tests, Radiotherapy; Adjuvant, Recurrence, Sensitivity and Specificity, Survival Analysis, Sweden, Treatment Outcome
Identifiers
urn:nbn:se:umu:diva-5971 (URN)16864166 (PubMedID)
Available from: 2007-12-04 Created: 2007-12-04 Last updated: 2018-06-09Bibliographically approved
Svensson, S., Jirström, K., Rydén, L., Roos, G., Emdin, S., Ostrowski, M. C. & Landberg, G. (2005). ERK phosphorylation is linked to VEGFR2 expression and Ets-2 phosphorylation in breast cancer and is associated with tamoxifen treatment resistance and small tumours with good prognosis. Oncogene, 24(27), 4370-4379
Open this publication in new window or tab >>ERK phosphorylation is linked to VEGFR2 expression and Ets-2 phosphorylation in breast cancer and is associated with tamoxifen treatment resistance and small tumours with good prognosis
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2005 (English)In: Oncogene, ISSN 0950-9232, E-ISSN 1476-5594, Vol. 24, no 27, p. 4370-4379Article in journal (Refereed) Published
Abstract [en]

Extracellular signal-regulated kinase (ERK)1/2 signalling mediates communication between growth factor receptors and the cell nucleus and has been linked to several key events in the transformation process such as proliferation and invasion. We therefore sought to delineate the degree of phosphorylated ERK1/2 in breast cancer and potential links to upstream receptors such as VEGFR2, ErbB2, downstream targets, such as Ets-2, as well as clinico-pathological parameters, clinical outcome and response to tamoxifen. ERK1/2 phosphorylation was assessed by immunohistochemistry using a phospho-specific ERK1/2 antibody in three breast cancer cohorts including a total of 886 tumours arranged in tissue arrays. Cohort I consisted of 114 patients, cohort II of 248 postmenopausal patients randomized to either 2 years of tamoxifen or no adjuvant treatment and cohort III of 524 patients. Surprisingly, ERK1/2 phosphorylation correlated inversely with tumour size. Phosphorylated ERK1/2 was further associated with the presence of VEGFR2 (cohorts II and III) and the degree of phosphorylated Ets-2, indicating in vivo, a signalling cascade from VEGFR2 via ERK1/2 to Ets-2 phosphorylation. Interestingly, ERK1/2 phosphorylation correlated with better survival in untreated patients independently of lymph-node status and tumour size indicating that ERK1/2 signalling might be associated with a less aggressive phenotype. Finally, patients with oestrogen receptor positive and ERK1/2 phosphorylated tumours also had an impaired tamoxifen response.

Place, publisher, year, edition, pages
Basingstoke: Macmillan Press, 2005
Keywords
Adult, Aged, Aged; 80 and over, Antibodies/immunology, Antibody Specificity, Breast Neoplasms/drug therapy/enzymology/*metabolism/pathology, Cohort Studies, Drug Resistance; Neoplasm, Extracellular Signal-Regulated MAP Kinases/*metabolism, Gene Expression Regulation; Neoplastic, Humans, Immunohistochemistry, Middle Aged, Oligonucleotide Array Sequence Analysis, Phosphorylation/drug effects, Prognosis, Protein Array Analysis, Proto-Oncogene Protein c-ets-2, Proto-Oncogene Proteins/*metabolism, Survival Rate, Tamoxifen/*pharmacology/therapeutic use, Trans-Activators/*metabolism, Treatment Outcome, Vascular Endothelial Growth Factor Receptor-2/*metabolism
Identifiers
urn:nbn:se:umu:diva-15233 (URN)10.1038/sj.onc.1208626 (DOI)15806151 (PubMedID)
Available from: 2007-12-04 Created: 2007-12-04 Last updated: 2018-06-09Bibliographically approved
Dejmek, J., Leandersson, K., Manjer, J., Bjartell, A., Emdin, S., Vogel, W. F., . . . Andersson, T. (2005). Expression and signaling activity of Wnt-5a/discoidin domain receptor-1 and Syk plays distinct but decisive roles in breast cancer patient survival.. Clin Cancer Res, 11(2 Pt 1), 520-8
Open this publication in new window or tab >>Expression and signaling activity of Wnt-5a/discoidin domain receptor-1 and Syk plays distinct but decisive roles in breast cancer patient survival.
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2005 (English)In: Clin Cancer Res, ISSN 1078-0432, Vol. 11, no 2 Pt 1, p. 520-8Article in journal (Refereed) Published
Keywords
Breast Neoplasms/*metabolism/mortality/pathology, Cell Adhesion/physiology, Enzyme Precursors/*metabolism, Epithelial Cells/metabolism, Humans, Integrin beta Chains/pharmacology, Intracellular Signaling Peptides and Proteins, Membrane Proteins/*metabolism, Neoplasm Invasiveness/pathology, Neoplasms; Ductal; Lobular; and Medullary/metabolism/mortality/pathology, Protein Biosynthesis, Protein-Tyrosine Kinases/*metabolism, Proto-Oncogene Proteins/*metabolism, Receptor Protein-Tyrosine Kinases/*metabolism, Signal Transduction, Survival Rate, Transcription; Genetic, Tumor Cells; Cultured, Wnt Proteins
Identifiers
urn:nbn:se:umu:diva-5967 (URN)15701836 (PubMedID)
Available from: 2007-12-04 Created: 2007-12-04 Last updated: 2018-06-09Bibliographically approved
Ljuslinder, I., Malmer, B., Golovleva, I., Thomasson, M., Grankvist, K., Höckenström, T., . . . Henriksson, R. (2005). Increased copy number at 3p14 in breast cancer. Breast Cancer Research, 7(5), R719-R727
Open this publication in new window or tab >>Increased copy number at 3p14 in breast cancer
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2005 (English)In: Breast Cancer Research, ISSN 1465-5411, E-ISSN 1465-542X, Vol. 7, no 5, p. R719-R727Article in journal (Refereed) Published
Keywords
myocardial ischemia, pacing, vectorcardiography, electrocardiography, heart rate, myocardial lactate
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:umu:diva-14494 (URN)10.1186/bcr1279 (DOI)16168117 (PubMedID)
Available from: 2007-12-04 Created: 2007-12-04 Last updated: 2018-06-09Bibliographically approved
Rydén, L., Stendahl, M., Jonsson, H., Emdin, S., Bengtsson, N. O. & Landberg, G. (2005). Tumor-specific VEGF-A and VEGFR2 in postmenopausal breast cancer patients with long-term follow-up: Implication of a link between VEGF pathway and tamoxifen response. Breast Cancer Research and Treatment, 89(2), 135-143
Open this publication in new window or tab >>Tumor-specific VEGF-A and VEGFR2 in postmenopausal breast cancer patients with long-term follow-up: Implication of a link between VEGF pathway and tamoxifen response
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2005 (English)In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 89, no 2, p. 135-143Article in journal (Refereed) Published
Abstract [en]

Vascular endothelial growth factor (VEGF-A) is considered a prognostic indicator for clinical outcome in breast cancer. Conflicting results nevertheless exist and there is a need for larger studies including untreated patients in order to clarify the importance of tumor-specific VEGF-A regarding prognosis as well as potential links to predictive treatment information. VEGF-A and its receptor, vascular endothelial growth receptor 2 (VEGFR2), were therefore analyzed by immunohistochemistry in postmenopausal breast cancers enrolled in a clinical trial where patients were randomized to adjuvant tamoxifen treatment (n=124) for 2 years or no treatment (n=127) with a median follow-up of 18 years. The tumors were arranged in a tumor tissue microarray system enabling parallell analysis of the angiogenic factors and hormone receptor status. Tumor-specific expression of VEGFR2 correlated strongly with expression of VEGF-A and progesterone receptor (PR) negativity, whereas VEGF-A was not associated with hormone receptor status. Among patients with estrogen receptor (ER) positive (fraction > 10%) tumors, there was a statistically significant tamoxifen response in VEGF-A negative tumors at both 10-year and 18-year disease-free survival (DFS), contrasting to VEGF-A positive tumors who had no beneficial effect of tamoxifen. A treatment-interaction variable indicated a marked difference in tamoxifen response depending on VEGFA-status in terms of DFS at 10 and 18 years of follow-up, p=0.046 and p=0.039, respectively. VEGFR2 status did not yield significant predicitve information for tamoxifen response in patients with ER fraction > 10%, whereas in patients with ER fraction > 90% both VEGF-A and VEGFR2 status were associated with tamoxifen treatment effect.

Place, publisher, year, edition, pages
The Hague: Nijhoff, 2005
Keywords
Aged, Antineoplastic Agents; Hormonal/*pharmacology/*therapeutic use, Breast Neoplasms/*drug therapy/*pathology, Chemotherapy; Adjuvant, Female, Follow-Up Studies, Humans, Immunohistochemistry, Middle Aged, Postmenopause, Prognosis, Tamoxifen/*pharmacology/*therapeutic use, Treatment Outcome, Tumor Markers; Biological/*analysis, Vascular Endothelial Growth Factor A/*blood, Vascular Endothelial Growth Factor Receptor-2/*blood
Identifiers
urn:nbn:se:umu:diva-5966 (URN)10.1007/s10549-004-1655-7 (DOI)15692755 (PubMedID)
Available from: 2007-12-04 Created: 2007-12-04 Last updated: 2018-06-09Bibliographically approved

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