Identification of non-responders to her2 inhibitors

Abstract

The present invention relates to means and methods for the identification of non-responders to a HER2 inhibitor, whereby one or more mutations in exon 9 of Phosphoinositol-3 kinase (PIK3CA) indicate non-responsiveness.

1 - 47 . (canceled) 
     
     
         48 . A method for detecting the presence of a mutation in exon 9 of Phosphoinositol-3 kinase (PIK3CA) in a sample from a patient with HER2-positive cancer comprising:
 i) obtaining a nucleic acid sample from the patient;   ii) contacting the nucleic acid sample from the patient with primers that specifically amplify a target sequence in exon 9 of PIK3CA and a probe that specifically hybridizes to a mutation in the target sequence in exon 9 of PIK3CA;   iii) carrying out an amplification reaction to generate a target sequence amplification product; and   iv) detecting the presence of a mutation in exon 9 of PIK3CA by detecting hybridization of the probe to the amplification product, wherein the presence of a mutation in exon 9 is detected and the presence of a mutation in exon 20 is not detected.   
     
     
         49 . The method of  claim 48 , wherein the HER2-positive cancer is breast cancer. 
     
     
         50 . The method of  claim 49 , wherein the breast cancer is early-stage breast cancer. 
     
     
         51 . The method of  claim 48 , wherein the mutation is one or more of the mutations E542 E545K, E545A and E545G in exon 9 of PIK3CA. 
     
     
         52 . The method of  claim 48 , further comprising treating the patient with a HER2 inhibitor if a mutation in exon 9 of PIK3CA is not detected. 
     
     
         53 . The method of  claim 52 , wherein the HER2-inhibitor is an anti-HER2 antibody. 
     
     
         54 . The method of  claim 53 , wherein the anti-HER2 antibody is pertuzumab. 
     
     
         55 . A method of treating a patient with a HER2-positive cancer comprising:
 i) obtaining a nucleic acid sample from the patient;   ii) contacting the nucleic acid sample from the patient with primers that specifically amplify a target sequence in exon 9 of PIK3CA and a probe that specifically hybridizes to a mutation in the target sequence in exon 9 of PIK3CA;   iii) carrying out an amplification reaction to generate a target sequence amplification product;   iv) detecting the presence of a mutation in exon 9 of PIK3CA by detecting hybridization of the probe to the amplification product; and   v) treating the patient with a HER2 inhibitor if a mutation in exon 9 of PIK3CA is not detected.   
     
     
         56 . The method of  claim 55 , wherein the HER2-positive cancer is breast cancer. 
     
     
         57 . The method of  claim 56 , wherein the breast cancer is early-stage breast cancer. 
     
     
         58 . The method of  claim 55 , wherein the mutation is one or more of the mutations E542 E545K, E545A and E545G in exon 9 of PIK3CA. 
     
     
         59 . The method of  claim 55 , wherein the HER2-inhibitor is an anti-HER2 antibody. 
     
     
         60 . The method of  claim 55 , wherein the anti-HER2 antibody is pertuzumab.