DNA REPAIR SIGNATURE AND PREDICTION OF RESPONSE FOLLOWING CANCER THERAPY

1 . A method of typing a sample of an individual with breast cancer, said sample comprising breast cancer cells or comprising gene expression products from breast cancer cells, the method comprising:

(i) isolating RNA from the sample obtained from the individual;

(ii) determining an expression level of at least 7 marker genes to thereby provide an expression profile of the marker genes, wherein the marker genes are selected from the genes listed in Table 1;

(iii) comparing the individual's expression profile to a reference expression profile of the at least 7 marker genes;

thereby typing the sample for a response following treatment with a poly ADP ribose polymerase (PARP) inhibitor.

2 . The method according to claim 1 , wherein the ample is either a fresh frozen or a formalin-fixed paraffin-embedded sample.

3 . The method according to claim 1 , wherein an individual who is typed as positively responding to a PARP inhibitor is treated with a PARP inhibitor.

4 . The method according to claim 1 , wherein treatment with a PARP inhibitor is combined with a platinum-based compound.

5 . The method according to claim 1 , wherein the determination of the expression profile is performed using RNA-sequencing or microarray gene expression analysis.

6 . The method according to claim 1 , wherein the expression profile comprises at least 8 different marker genes, 10 different marker genes, preferably at least 20 different marker genes, more preferably at least 30 different marker genes, more preferably at least 40 different marker genes, more preferably at least 50 different marker genes selected from the genes listed in Table 1, most preferably all marker genes listed in Table 1.

7 . The method according to claim 1 , wherein the reference expression profile is composed of the average expression levels of the marker genes specified in step (ii) of individuals having a positive response to a PARP inhibitor, of individuals not having a positive response to a PARP inhibitor; or of a mixture of individuals having a positive response to a PARP inhibitor and individuals not having a positive response to a PARP inhibitor.

8 . The method according to claim 1 , wherein the individual's expression profile is compared to two reference expression profiles, wherein one reference expression profile is composed of the average expression levels of the marker genes specified in step (ii) of individuals having a positive response to a PARP inhibitor and the other reference expression profile is composed of the average expression level of the marker genes specified in step (ii) of individuals not having a positive response to a PARP inhibitor.

9 . The method according to claim 1 , wherein the response is a pathologic complete response (pCR).

10 . A method of treating an individual with breast cancer, comprising:

typing of a sample from said individual using the method according to claim 1 ;

treating the individual that is typed as having a positive response to a PARP inhibitor with a PARP inhibitor, optionally in combination with a platinum-based compound and/or a taxane; and

treating the individual that is typed as not having a positive response to a PARP inhibitor with chemotherapy, immunotherapy, or a combination thereof.

11 . The method according to claim 10 , wherein the PARP inhibitor comprises veliparib.

12 . The method according to claim 10 , wherein the PARP inhibitor comprises olaparib.

13 . The method according to claim 10 , wherein the PARP inhibitor comprises talazoparib.

14 . The method of claim 10 , wherein the PARP inhibitor is combined with a platinum-based compound.

15 . The method according to claim 14 , wherein the platinum-based compound comprises carboplatin.