Use of 70-gene signature to predict prognosis of patients with node-negative breast cancer: a prospective community-based feasibility study (RASTER)

Bueno-de-Mesquita, Jolien M.; Harten, Wim H. van; Retèl, Valesca; Veer, Laura J. van’t; Dam, F.S.A.M. van; Karsenberg, Kim; Douma, Kirsten F. L.; Tinteren, Harm van; Peterse, Johannes L.; Wesseling, Jelle; Wu, Tin S.; Atsma, Douwe E.; Rutgers, Emiel J.; Brink, Guido; Floore, Arno; Glas, Annuska M.; Roumen, R. M. H.; Bellot, Frank E.; Krimpen, C. van; Rodenhuis, S.; Vijver, Marc J. van de; Linn, Sabine C.

doi:10.1016/s1470-2045(07)70346-7

Cited by 248 publications

(232 citation statements)

References 25 publications

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“…This finding has several important clinical implications. Currently, the 70 gene profile is used to select patients for adjuvant chemotherapy whereby chemotherapy is frequently withheld for tumors with a good prognosissignature [27]. Our results add justification to this policy; not only is the absolute risk of relapse lower in these patients, but their tumors are also less sensitive to chemotherapy.…”

Section: Discussionmentioning

confidence: 64%

The 70-gene signature as a response predictor for neoadjuvant chemotherapy in breast cancer

Straver

Glas

Hannemann

et al. 2009

Breast Cancer Res Treat

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226

118

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Section: Discussionmentioning

confidence: 64%

The 70-gene signature as a response predictor for neoadjuvant chemotherapy in breast cancer

Straver

Glas

Hannemann

et al. 2009

Breast Cancer Res Treat

Self Cite

226

118

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“…The 70-gene prognosis signature has been used in the Dutch RASTER-study (Netherlands Cancer Institute in collaboration with the Dutch Health Care Insurance Board) [41] and is currently used in the international MINDACT-trial (TRANSBIG consortium in collaboration with the European Organisation for Research and Treatment of Cancer) [42].…”

Section: Discussionmentioning

confidence: 99%

Validation of 70-gene prognosis signature in node-negative breast cancer

Bueno-de-Mesquita

Linn

Keijzer

et al. 2008

Breast Cancer Res Treat

151

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International audienceThe 70-gene prognosis signature (van't Veer et al., Nature 415(6871):530–536, 2002) may improve the selection of lymph node-negative breast cancer patients for adjuvant systemic therapy. Optimal validation of prognostic classifiers is of great importance and we therefore wished to evaluate the prognostic value of the 70-gene prognosis signature in a series of relatively recently diagnosed lymph node negative breast cancer patients. We evaluated the 70-gene prognosis signature in an independent representative series of patients with invasive breast cancer ( = 123; <55 years; pT1-2N0; diagnosed between 1996 and 1999; median follow-up 5.8 years) by classifying these patients as having a good or poor prognosis signature. In addition, we updated the follow-up of the node-negative patients of the previously published validation-series (Van de Vijver et al., N Engl J Med 347(25):1999–2009, 2002; = 151; median follow-up 10.2 years). The prognostic value of the 70-gene prognosis signature was compared with that of four commonly used clinicopathological risk indexes. The endpoints were distant metastasis (as first event) free percentage (DMFP) and overall survival (OS). The 5-year OS was 82 ± 5% in poor (48%) and 97 ± 2% in good prognosis signature (52%) patients (HR 3.4; 95% CI 1.2–9.6; = 0.021). The 5-years DMFP was 78 ± 6% in poor and 98 ± 2% in good prognosis signature patients (HR 5.7; 95% CI 1.6–20; = 0.007). In the updated series ( = 151; 60% poor vs. 40% good), the 10-year OS was 51 ± 5% and 94 ± 3% (HR 10.7; 95% CI 3.9–30; < 0.01), respectively. The DMFP was 50 ± 6% in poor and 86 ± 5% in good prognosis signature patients (HR 5.5; 95% CI 2.5–12; < 0.01). In multivariate analysis, the prognosis signature was a strong independent prognostic factor in both series, outperforming the clinicopathological risk indexes. The 70-gene prognosis signature is also an independent prognostic factor in node-negative breast cancer patients for women diagnosed in recent years

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“…Whether prognostic signatures will reduce the number of patients undergoing toxic chemotherapy remains unclear. For example, although the MammaPrint 70-gene signature is expected to identify 10-15% of patients who might be spared chemotherapy, results of a recent finalized feasibility study suggest this outcome is overly optimistic [25]. Transcriptomic profiling has also proved constrained as a predictor of therapeutic response.…”

Section: Introductionmentioning

confidence: 99%

The cell cycle and cancer

Williams

Stoeber

2011

The Journal of Pathology

579

406

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Deregulation of the cell cycle underlies the aberrant cell proliferation that characterizes cancer and loss of cell cycle checkpoint control promotes genetic instability. During the past two decades, cancer genetics has shown that hyperactivating mutations in growth signalling networks, coupled to loss of function of tumour suppressor proteins, drives oncogenic proliferation. Gene expression profiling of these complex and redundant mitogenic pathways to identify prognostic and predictive signatures and their therapeutic targeting has, however, proved challenging. The cell cycle machinery, which acts as an integration point for information transduced through upstream signalling networks, represents an alternative target for diagnostic and therapeutic interventions. Analysis of the DNA replication initiation machinery and mitotic engine proteins in human tissues is now leading to the identification of novel biomarkers for cancer detection and prognostication, and is providing target validation for cell cycle-directed therapies.

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Use of 70-gene signature to predict prognosis of patients with node-negative breast cancer: a prospective community-based feasibility study (RASTER)

Cited by 248 publications

References 25 publications

The 70-gene signature as a response predictor for neoadjuvant chemotherapy in breast cancer

The 70-gene signature as a response predictor for neoadjuvant chemotherapy in breast cancer

Validation of 70-gene prognosis signature in node-negative breast cancer

The cell cycle and cancer

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