# US 2019/0169693 A1 · Method for the diagnosis, prognosis and treatment of breast cancer metastasis

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- Number: US 2019/0169693 A1
- Document ID: US20190169693A1
- Status: Published application
- Kind: A1
- Application number: 16/028,530
- Filed: 2018-07-06
- Published: 2019-06-06
- Earliest claimed: 2010-10-06
- Assignees: Fundació Institut de Recerca Biomèdica (IRB Barcelona); Institució Catalana De Recerca I Estudis AvançAts
- Applicants: Fundacio Institut De Recerca Biomedica (Irb Barcelona ); Institucio Catalana De Recerca I Estudis Avancats
- Inventors: Roger GOMIS; Maria Tarragona; Anna Arnal; Milica Pavlovic
- Web page: https://patentgrep.com/patent/US20190169693A1

## CPC

- C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575)
- A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives
- A61P 19/08: for bone diseases, e.g. rachitism, Paget's disease
- A61P 35/00: Antineoplastic agents
- A61P 35/04: specific for metastasis
- C07F 9/6506: having the nitrogen atoms in positions 1 and 3
- C12Q 2600/106: Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
- C12Q 2600/112: Disease subtyping, staging or classification
- C12Q 2600/118: Prognosis of disease development
- C12Q 2600/158: Expression markers
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22)

## Abstract

The present invention relates to a method for the diagnosis or the prognosis of metastasis in breast cancer which comprises determining if the c-MAF gene is amplified in a primary tumor sample. Likewise, the invention also relates to a method for the diagnosis or the prognosis of metastasis in ER− breast cancer, as well as to a method for determining the tendency to develop bone metastasis with respect to metastasis in other organs, which comprise determining the c-MAF gene expression level. Finally, the invention relates to the use of a c-MAF inhibitor as therapeutic target for treating the ER− breast cancer metastasis.

## Claims

### Claim at position 1

1-32. (canceled)

### Claim 33

A method for the treatment of bone metastasis in a subject suffering breast cancer with an elevated c-MAF expression level, copy number or amplification in a tumor tissue sample with respect to a control sample comprising administering an agent capable of avoiding, treating, or preventing bone degradation to said subject suffering breast cancer, wherein said subject has been determined to have an elevated c-MAF expression level, copy number or amplification.

### Claim 34 (depends on 33)

The method according to claim 33, wherein the agent capable of avoiding, treating or preventing bone degradation is selected from the group consisting of: a bisphosphonate, a RANKL inhibitor, PTH or a PRG analog, strontium ranelate, an estrogen receptor modulator, calcitonin and a cathepsin K inhibitor.

### Claim 35 (depends on 34)

The method according to claim 34, wherein the RANKL inhibitor is selected from the group consisting of: a RANKL specific antibody and osteoprotegerin.

### Claim 36 (depends on 35)

The method according to claim 35, wherein the RANKL specific antibody is denosumab.

### Claim 37 (depends on 34)

The method according to claim 34, wherein the bisphosphonate is zoledronic acid.

### Claim 38 (depends on 34)

The method according to claim 34, wherein the bisphosphonate is clodronate.

### Claim 39 (depends on 33)

The method according to claim 33, wherein the breast cancer is ER+ or ER−.

### Claim 40 (depends on 33)

The method according to claim 33, wherein the bone metastasis is osteolytic metastasis.

### Claim 41 (depends on 33)

The method according to claim 33, wherein the quantification of the expression level, amplification or copy number comprises quantifying the messenger RNA (mRNA) of said gene, or a fragment of said mRNA, the complementary DNA (cDNA) of said gene, or a fragment of said cDNA or quantifying the level of protein encoded by said gene.

### Claim 42 (depends on 41)

The method according to claim 41 wherein the expression level, amplification or copy number is quantified by means of a quantitative polymerase chain reaction (PCR) or a DNA or RNA array.

### Claim 43 (depends on 41)

The method according to claim 41, wherein the level of protein is quantified by means of western blot, ELISA, in situ hybridization, or a protein array.

### Claim 44 (depends on 43)

The method according to claim 43, wherein the in situ hybridization is fluorescence in situ hybridization (FISH), chromogenic in situ hybridization (CISH) or silver in situ hybridization (SISH).

### Claim 45 (depends on 44)

The method according to claim 44, wherein the in situ hybridization is fluorescence in situ hybridization (FISH).

### Claim 46 (depends on 33)

The method according to claim 33, wherein the amplification of the c-MAF gene is determined by means of determining the amplification of the locus 16q22-q24.

### Claim 47 (depends on 33)

The method according to claim 33, wherein the amplification of the c-MAF gene is determined by means of using a c-MAF gene-specific probe.

### Claim 48 (depends on 47)

The method according to claim 47, wherein the c-MAF gene-specific probe is a fluorescent probe.

### Claim 49 (depends on 33)

The method according to claim 33, wherein the control sample is a tumor tissue sample of breast cancer from a subject who has not suffered metastasis.

### Claim 50 (depends on 33)

The method according to claim 33, wherein the increase of c-MAF expression is at least about 1.1 times, 1.5 times, 5 times, 10 times, 20 times, 30 times, 40 times, 50 times, 60 times, 70 times, 80 times, 90 times, 100 times or greater than the control sample.

### Claim 51 (depends on 33)

The method according to claim 33, wherein the c-MAF gene is amplified at least about 1.1 times, 1.5 times, 5 times, 10 times, 20 times, 30 times, 40 times, 50 times, 60 times, 70 times, 80 times, 90 times, 100 times or greater compared with the control sample

### Claim 52 (depends on 33)

The method according to claim 33, wherein said subject has been determined to have an elevated c-MAF expression level, copy number or amplification in a tumor tissue sample with respect to a control sample

### Claim 53

A method for the treatment of bone metastasis in a subject suffering breast cancer comprising:
(i) obtaining a breast tumor tissue sample from the human subject;
(ii) detecting c-MAF expression level, copy number or amplification in the breast tumor tissue sample;
(iii) comparing the expression level, copy number or amplification obtained in (ii) with the expression level, copy number or amplification of the c-MAF gene in a control sample, and,
(iv) administering an agent capable of avoiding, treating, or preventing bone degradation to said subject suffering breast cancer, wherein said subject has been determined to have an elevated c-MAF expression level, copy number or amplification.

### Claim 54 (depends on 53)

The method according to claim 53, wherein the agent capable of avoiding, treating or preventing bone degradation is selected from the group consisting of: a bisphosphonate, a RANKL inhibitor, PTH or a PRG analog, strontium ranelate, an estrogen receptor modulator, calcitonin and a cathepsin K inhibitor.

### Claim 55 (depends on 54)

The method according to claim 54, wherein the RANKL inhibitor is selected from the group consisting of: a RANKL specific antibody and osteoprotegerin.

### Claim 56 (depends on 55)

The method according to claim 55, wherein the RANKL specific antibody is denosumab.

### Claim 57 (depends on 54)

The method according to claim 54, wherein the bisphosphonate is zoledronic acid.

### Claim 58 (depends on 54)

The method according to claim 54, wherein the bisphosphonate is clodronate.

### Claim 59 (depends on 53)

The method according to claim 53, wherein the breast cancer is ER+ or ER−.