Two years of adjuvant tamoxifen in premenopausal patients with breast cancer: a randomised, controlled trial with long-term follow-up

Rydén, Lisa; Jönsson, Per; Chebil, Gunilla; Dufmats, Monika; Fernö, Mårten; Jirström, Karin; Källström, Ann Christin; Landberg, Göran; Stål, Olle; Thorstenson, Sten; Nordenskjöld, Bo

doi:10.1016/j.ejca.2004.06.030

Cited by 95 publications

(115 citation statements)

References 20 publications

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“…30 ER and PR were scored as positive if the fraction of positive tumour cells was >10%, which is in line with current clinical recommended determines. HIF-1a protein was evaluated by 2 investigators scoring the tissue array samples according to the fraction of positively stained nuclei; since active HIF-1a is located only in the nucleus, cytoplasmic staining was discarded.…”

Section: Immunohistochemical Evaluationmentioning

confidence: 79%

“…Between 1984 and 1991, 564 premenopausal women with primary breast cancer from the South and Southeast region of Sweden were enrolled in a clinical trial 30 and randomised to adjuvant tamoxifen treatment (20 or 40 mg daily), n 5 276, for 2 years versus control, n 5 288. The aim of our study was to compare the effect of tamoxifen on RFS (primary outcome).…”

Section: Methodsmentioning

confidence: 99%

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Hypoxia inducible factor‐1α is a prognostic marker in premenopausal patients with intermediate to highly differentiated breast cancer but not a predictive marker for tamoxifen response

Kronblad

Jirström

Rydén

et al. 2006

Intl Journal of Cancer

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Hypoxia is common in many solid tumours, including breast cancer. Hypoxia triggers the expression of hypoxia inducible factor1a (HIF-1a), and HIF-1a has been associated with an impaired prognosis in breast cancer and down-regulation of the oestrogen receptor (ER), potentially affecting the treatment efficiency of antioestrogens. The role of HIF-1a regarding prognostic and treatment predictive information in breast cancer has not been established and we therefore analyzed HIF-1a using immunohistochemistry in a cohort of 377 premenopausal stage II breast cancers arranged in a tissue microarray. The patients were included in a randomized trial with either 2 years of tamoxifen or no adjuvant treatment. The tamoxifen treatment effect could be studied in subgroups of breast cancer and pure prognostic information could be scrutinized for untreated control patients. HIF-1a was scored as positive in 24% of the tumours and correlated positively to tumour size, Nottingham histological grade (NHG), Ki-67, Her2 and cyclin E expression and negatively to lymph node status, cyclin D1, ER and PR (progesterone receptor) expression. Surprisingly, there was no difference in tamoxifen response for patients with high or low HIF-1a expressing tumours. In lymph node-positive patients as well as NHG 1/2 tumours, high HIF-1a protein expression was significantly associated with an impaired recurrence-free survival (p 5 0.014, 0.018). When analyzing the subgroup of NHG 1/2 tumours, a high HIF-1a expression was the only independent significant prognostic marker in multivariate analysis, including standard prognostic markers, suggesting that HIF-1a might be a useful prognostic marker in this subgroup of breast cancer, with a rather good but diverse prognosis. ' 2005 Wiley-Liss, Inc.

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Section: Immunohistochemical Evaluationmentioning

confidence: 79%

Section: Methodsmentioning

confidence: 99%

Hypoxia inducible factor‐1α is a prognostic marker in premenopausal patients with intermediate to highly differentiated breast cancer but not a predictive marker for tamoxifen response

Kronblad

Jirström

Rydén

et al. 2006

Intl Journal of Cancer

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“…The postmenopausal patients were participants in a randomized clinical trial, comparing 2 and 5 years of adjuvant tamoxifen treatment [14]. The premenopausal patients were enrolled in a trial aimed at comparing the effect of tamoxifen treatment versus no treatment [15]. From this trial, only patients from the untreated cohort were chosen.…”

Section: Patientsmentioning

confidence: 99%

“…Nottingham histologic grade (NHG) were assessed as in clinical routine practice and as previously described [15][16][17]. Of 373 tumor samples analyzed, RNA expression data were obtained from 357 tumors, 264 were postmenopausal and 93 were premenopausal patients.…”

Section: Patientsmentioning

confidence: 99%

Exploring the two-gene ratio in breast cancer—independent roles for HOXB13 and IL17BR in prediction of clinical outcome

Jerevall

Brommesson

Strand

et al. 2007

Breast Cancer Res Treat

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“…The real cancer data set used is a compilation of data from five breast cancer studies, four Swedish and one Danish [15][16][17][18][19]. Time from diagnosis of primary breast cancer to first distant recurrence or last follow-up without distant recurrence was available for all patients.…”

Section: Study Populationmentioning

confidence: 99%

Training artificial neural networks directly on the concordance index for censored data using genetic algorithms

Kalderstam

Edén

Bendahl

et al. 2013

Artificial Intelligence in Medicine

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Training artificial neural networks directly on the concordance index for censored data using genetic algorithms. Kalderstam, J., Edén, P., Bendahl, P-O., Forsare, C., Fernö, M., & Ohlsson, M. (2013). Training artificial neural networks directly on the concordance index for censored data using genetic algorithms. Artificial Intelligence in Medicine, 58(2), 125-132. DOI: 10.1016/j.artmed.2013 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal A significant difference could however be seen when applied on the non-linear synthetic data set. In that case the ANN ensemble managed to achieve a cindex score of 0.90 whereas the cox model failed to distinguish itself from the random case (c-index = 0.49). Conclusions:We have found empirical evidence that ensembles of ANN models can be optimized directly on the c-index. Comparison with a Cox model indicates that near identical performance is achieved on a real cancer data set while on a non-linear data set the ANN model is clearly superior.

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Two years of adjuvant tamoxifen in premenopausal patients with breast cancer: a randomised, controlled trial with long-term follow-up

Cited by 95 publications

References 20 publications

Hypoxia inducible factor‐1α is a prognostic marker in premenopausal patients with intermediate to highly differentiated breast cancer but not a predictive marker for tamoxifen response

Hypoxia inducible factor‐1α is a prognostic marker in premenopausal patients with intermediate to highly differentiated breast cancer but not a predictive marker for tamoxifen response

Exploring the two-gene ratio in breast cancer—independent roles for HOXB13 and IL17BR in prediction of clinical outcome

Training artificial neural networks directly on the concordance index for censored data using genetic algorithms

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