Method for predicting the benefit from inclusion of taxane in a chemotherapy regimen in patients with breast cancer

Abstract

A method for predicting a benefit from inclusion of taxane in a chemotherapy regimen in a patient suffering from or at risk of developing recurrent neoplastic disease, in particular breast cancer. Said method comprises the steps of: a) determining in a tumor sample from said patient the expression levels of the marker genes S100P and PCSK6, and b) mathematically combining the expression level values of the genes PCSK6 and S100P to yield a combined score and comparing said combined score to a reference-value, including a cutoff, wherein a high combined score is indicative of a benefit from including a taxane in a chemotherapy regimen of said patient and a low combined score is indicative of not having a benefit from including a taxane in a chemotherapy regimen of said patient or c) mathematically combining the expression level value of PCSK6 and S100P with the expression values of other genes to yield a combined score and comparing said combined score to a reference-value, including a cutoff, wherein a high combined score is indicative of a benefit from including a taxane in a chemotherapy regimen of said patient and a low combined score is indicative of not having a benefit from including a taxane in a chemotherapy regimen of said patient.

1 . A method for predicting a benefit from inclusion of taxane in a chemotherapy regimen, including adjuvant and/or neoadjuvant chemotherapy, in a patient suffering from or at risk of developing recurrent neoplastic disease, in particular breast cancer, said method comprising the steps of:
 a) determining in a tumor sample from said patient the expression levels of the marker genes S100P and PCSK6,   and   b) mathematically combining the expression level values of the genes PCSK6 and S100P to yield a combined score and comparing said combined score to a reference-value, including a cutoff, wherein a high combined score is indicative of a benefit from including a taxane in a chemotherapy regimen of said patient and a low combined score is indicative of not having a benefit from including a taxane in a chemotherapy regimen of said patient   or   c) mathematically combining the expression level values of PCSK6 and S100P with the expression values of other genes to yield a combined score and comparing said combined score to a reference-value, including a cutoff, wherein a high combined score is indicative of a benefit from including a taxane in a chemotherapy regimen of said patient and a low combined score is indicative of not having a benefit from including a taxane in a chemotherapy regimen of said patient.   
     
     
         2 . The method of  claim 1 , wherein said expression level is determined as a non-protein such as a gene expression level. 
     
     
         3 . The method of  claim 1 , wherein said expression level is determined by at least one of the following methods:
 a PCR based method,   a microarray based method,   a hybridization based method,   a sequencing and/or   next generation sequencing approach.   
     
     
         4 . The method of  claim 1 , wherein said determination of expression levels is in a formalin-fixed paraffin-embedded tumor sample or in a fresh-frozen tumor sample. 
     
     
         5 . The method of  claim 1 , wherein the expression levels are determined as a pattern of expression relative to at least one reference gene or to a computed average expression value. 
     
     
         6 . The method of  claim 1 , wherein said step of mathematically combining the expression level values comprises a step of applying an algorithm to values representative of an expression level of S100P and PCSK6. 
     
     
         7 . The method of  claim 6 , wherein said algorithm is a linear combination of said values representative of an expression level of S100P and PCSK6. 
     
     
         8 . The method of  claim 6 , wherein a value for a representative of an expression level of a given gene is multiplied with a coefficient. 
     
     
         9 . The method of any one of the foregoing claims  claim 1 , wherein one, two or more thresholds are determined for said combined score and discriminated groups by applying the threshold on the combined score. 
     
     
         10 . The method of  claim 1 , wherein one, two or more thresholds are determined for said combined score and discriminated into (1) “predicted benefit” and “predicted non-benefit”, (2) “predicted benefit” and “predicted adverse effect”, (3) “predicted benefit”, “predicted indifferent effect” and “predicted adverse effect”, or more risk groups with different probabilities of benefit by applying the threshold on the combined score. 
     
     
         11 . The method of  claim 1 ,
 wherein a high combined score is indicative of a benefit from taxane-based treatment.   
     
     
         12 . The method of  claim 1 ,
 wherein information regarding clinical parameters of the patient is processed in the step of mathematically combining expression level values for the genes to yield a combined score.   
     
     
         13 . A kit for performing the method of  claim 1 , said kit comprising a set of oligonucleotides capable of specifically binding sequences or to sequences of fragments of the genes.