Ahmed, H.

Ezzeldien, M.

Hammad, S.

Kotb, A. M.

Osman, G. S.

Eldorado - Ressourcen aus und für Lehre, Studium und Forschung

EXCLI Journal 2016;15:867-869 – ISSN 1611-2156 
Received: December 12, 2016, accepted: December 19, 2016, published: December 23, 2016 
 
 
867 
Guest editorial: 
HIGHLIGHT REPORT:  
PREDICTING LATE METASTASIS IN BREAST CANCER 
 
Seddik Hammad1,2*, Gada S. Osman3, Mohamed Ezzeldien4, Hassan Ahmed5,  
Ahmed M. Kotb6,7 
 
1 Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine,  
South Valley University, Qena, Egypt 
2 Molecular Hepatology - Alcohol Associated Diseases, Department of Medicine II,  
Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany 
3 Department of Pathology, Faculty of Medicine, South Valley University, Qena, Egypt 
4 Department of Physics, Faculty of Science, South Valley University, Qena, Egypt 
5 Department of Physiology, Faculty of Veterinary Medicine, South Valley University, 
Qena, Egypt 
6 Institute of Anatomy and Cell Biology, University Medicine Greifswald, Greifswald,  
Germany 
7 Department of Anatomy and Histology, Faculty of Veterinary Medicine, Assiut University, 
Assiut, Egypt 
 
* corresponding author: Seddik.hammad@vet.svu.edu.eg 
 
 
http://dx.doi.org/10.17179/excli2016-843 
 
This is an Open Access article distributed under the terms of the Creative Commons Attribution License  
(http://creativecommons.org/licenses/by/4.0/). 
 
 
 
Recently, Birte Hellwig and colleagues 
from the Department of Statistics, TU Dort-
mund University have published a study to 
predict late metastasis in breast cancer (Hell-
wig et al., 2016). In breast cancer survival 
strongly depends on distant metastasis 
(Schmidt et al., 2008). Although, the risk of 
metastasis decreases with time after surgery, 
metastatic events do still occur more than five 
years after diagnosis (Karrison et al., 1999; 
Demicheli et al., 1996; Saphner et al., 1996). 
Prediction of these late metastatic events is of 
high relevance. On the one side, the patient’s 
distress would be alleviated if a low probabil-
ity of late metastatic recurrence could be pre-
dicted (Hellwig et al., 2016). On the other 
hand, high-risk patients could be integrated 
into extended endocrine therapy studies.  
In the present study Hellwig et al. (2016) 
used a sequential validation strategy to iden-
tify and validate genes that predict late metas-
tasis: they identified a first set of late genes in 
a breast cancer cohort (n=409), which was 
confirmed in an independent validation co-
hort (n=169) and additionally confirmed in a 
second validation cohort (n=923). The careful 
sequential validation that also includes a 
check for sample annotation errors (Grinberg 
et al., 2015) is certainly strength of the present 
study. The authors validated nine late-type 
genes, whereby the tumor angiogenesis mod-
ifier EPN3 was associated with increased and 
several ribosome-related genes with de-
creased risk of late breast cancer metastasis.  
In recent years numerous studies have 
been performed to predict prognosis of cancer 
EXCLI Journal 2016;15:867-869 – ISSN 1611-2156 
Received: December 12, 2016, accepted: December 19, 2016, published: December 23, 2016 
 
 
868 
(Hammad, 2013; Hammad et al., 2013; Mar-
chan, 2014a, b; Lohr et al., 2015). Often, 
prognostic factors are associated with prolif-
eration (Schmidt et al., 2008, 2012), immune 
cell infiltration (Lohr et al., 2013; Godoy et 
al., 2014), inflammation (Mattson et al., 2015; 
Sicking et al., 2014), tumor cell migration 
(Stock et al., 2015; Stewart et al., 2012), dis-
turbed circadian control (Cadenas et al., 2014; 
Ghallab, 2015) or antioxidant status (Mili-
cevic et al., 2014). However, most previous 
studies did not differentiate, whether prognos-
tic factors predict early or late metastasis. The 
present study of Hellwig and colleagues un-
derlines that the vast majority of all prognos-
tic genes in breast cancer predicts metastasis 
only up to approximately three years after sur-
gery. Only a small minority of prognostic 
genes maintains its significance at later peri-
ods. The relevance of the present study is that 
these ‘late genes’ have so far not been used 
for routine diagnosis of breast cancer recur-
rence risk and may lead to an improvement of 
the accuracy of already existing systems. 
 
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Highlight report: Predicting late metastasis in breast cancer

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Highlight report: Predicting late metastasis in breast cancer

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