Methods for assessing the treatment response of TNBC patients to neo-adjuvant chemotherapy by analysing CpG methylation
AssigneeTherawis Diagnostics GmbH
InventorsManfred Schmitt, Olaf G. Wilhelm, Rudolf Napieralski
Life of this patent
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Abstract
The present invention relates to methods for predicting the efficacy of anthracycline-based neo-adjuvant chemotherapy in triple-negative breast cancer. This is achieved by determining epigenetic changes within the PITX2 gene. Detection of the methylation state of Cp G sites in a genomic sequence of PITX2 allows an estimate of the response or failure of an individual breast cancer patient to neo-adjuvant therapy.
Claims12
A method of treating a human subject afflicted with triple-negative breast cancer (TNBC) comprising the steps:
- a) providing a breast cancer tissue sample from the subject;
- b) determining the methylation state of CpG dinucleotides within a genomic sequence of the homeodomain transcription factor 2 (PITX2) gene, wherein said CpG dinucleotides are the CpG dinucleotides that are in the nucleotide range of 10952-10967 of SEQ ID NO:
- 1, within said breast cancer tissue sample;
- c) selecting a treatment regimen for the subject selected from the group consisting of:
- (i) in the absence of PITX2 hypomethylation of said CpG dinucleotides treating the subject with an anthracycline-based neoadjuvant TNBC chemotherapy treatment;
- and
- (ii) in the presence of PITX2 hypomethylation of said CpG dinucleotides treating the subject with a non-anthracycline-based TNBC therapy treatment;
- and
- d) treating the human subject with the selected treatment regimen of step c).
A method for treating a human subject afflicted with triple-negative breast cancer (TNBC) comprising:
- a) isolating genomic DNA comprising the PITX2 gene from a breast cancer tissue sample of the subject;
- b) converting in the PITX2 gene of said genomic DNA, or a fragment thereof, cytosine unmethylated in the 5-position to uracil;
- c) amplifying in said converted genomic DNA a fragment of the PITX2 gene comprising the region corresponding to SEQ ID NO:
- 17
- d) determining, in the amplified fragment, the methylation state of CpG dinucleotides the PITX2 gene, wherein said CpG dinucleotides are the CpG dinucleotides that are in the nucleotide range of 10952-10967 of SEQ ID NO:
- 1;
- e) selecting a treatment regimen for the subject selected from the group consisting of:
- (i) in the absence of PITX2 hypomethylation of said CpG dinucleotides treating the subject with an anthracycline-based neoadjuvant TNBC chemotherapy treatment;
- and
- (ii) in the presence of PITX2 hypomethylation of said CpG dinucleotides treating the subject with a non-anthracycline-based TNBC therapy treatment;
- and
- d) treating the human subject with the selected treatment regimen of step c).
Dependencies are inferred from the claim text.