Method for the diagnosis, prognosis and treatment of breast cancer metastasis
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.
1. An in vitro method for diagnosing the presence and/or risk of developing bone metastasis and/or bone metastasis recurrence in a human subject and for treating bone metastasis or bone metastasis recurrence, or the increased risk of developing bone metastasis and/or recurrence, wherein the human subject has ER+ breast cancer, comprising:
(i) obtaining a breast tumor tissue sample from the human subject;
(ii) detecting c-MAF gene amplification in the breast tumor tissue sample by performing a nucleic acid based detection assay on the tumor tissue sample;
(iii) diagnosing the human subject as having bone metastasis and/or recurrence or at increased risk of developing bone metastasis and/or recurrence based on the detection of c-MAF gene amplification in the tumor tissue sample as compared to a control sample; and
(iv) administering a therapeutically effective amount of a bisphosphonate or a RANKL inhibitor to the human subject diagnosed as having bone metastasis and/or recurrence or at increased risk of developing bone metastasis and/or recurrence to thereby treat bone metastasis or bone metastasis recurrence, or the increased risk of developing bone metastasis and/or recurrence.
2. The method according to claim 1 , wherein the control sample is a tumor tissue sample of breast cancer from a subject who has not suffered metastasis.
3. The method according to claim 1 , wherein detecting c-MAF gene amplification comprises performing in situ hybridization or polymerase chain reaction (PCR).
4. The method according to claim 1 , wherein the bone metastasis is osteolytic metastasis.
5. The method according to claim 1 , wherein the agent capable of avoiding or preventing bone degradation is a RANKL inhibitor.
6. The method according to claim 5 , wherein the RANKL inhibitor is selected from the group consisting of a RANKL, specific antibody and osteoprotegerin.
7. The method according to claim 6 , wherein the RANKL specific antibody is denosumab.
8. The method according to claim 1 , wherein the bisphosphonate is zoledronic acid.
9. The method according to claim 1 , 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.
10. The method according to claim 3 , wherein the in situ hybridization is fluorescence in situ hybridization (FISH), chromogenic in situ hybridization (CISH) or silver in situ hybridization (SISH).
11. The method according to claim 10 , wherein the in situ hybridization is fluorescence in situ hybridization (FISH).
12. The method according to claim 1 , wherein detecting c-MAF gene amplification comprises using a c-MAF gene-specific probe and wherein the c-MAF gene-specific probe is a fluorescent probe.
13. The method according to claim 12 , wherein the fluorescent probe is used in fluorescence in situ hybridization (FISH).