Granted Patent
B2
US 12,312,642 · App. 17/385,568 · Granted May 27, 2025
Method for the diagnosis, prognosis and treatment of breast cancer metastasis
Inventors:
Roger Gomis (Barcelona, ES); Maria Tarragona (Barcelona, ES); Anna Arnal (Barcelona, ES); Milica Pavlovic (Lajkovac, RS)
Assignees:
FUNDACIO INSTITUT DE RECERCA BIOMEDICA (IRB BARCELONA); INSTITUCIO CATALANA DE RECERCA I ESTUDIS AVANCATS
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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 (26)
1. A method for the treatment of bone metastasis in a subject suffering ER+ breast cancer comprising administering an agent capable of avoiding, treating, or preventing bone degradation to said subject suffering ER+ breast cancer, wherein said subject has been determined to have an elevated c-MAF expression level in a primary breast cancer tumor tissue sample with respect to a control sample, wherein the control sample is a tumor tissue sample of breast cancer from a subject who has not suffered metastasis, 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, wherein the subject is a human, wherein the subject has been determined to have an elevated c-MAF expression level through quantification of the c-MAF expression level, and wherein the quantification of the expression level comprises quantifying the messenger RNA (mRNA) of c-MAF, or a fragment of said mRNA, or quantifying the complementary DNA (cDNA) of c-MAF, or a fragment of said cDNA, wherein the c-MAF expression level is considered to be elevated when the expression level in the primary breast cancer tumor tissue sample is at least 5 times or greater than the control sample.
2. The method according to claim 1 , wherein the RANKL inhibitor is selected from the group consisting of: a RANKL specific antibody and osteoprotegerin.
3. The method according to claim 2 , wherein the RANKL specific antibody is denosumab.
4. The method according to claim 1 , wherein the bisphosphonate is zoledronic acid.
5. The method according to claim 1 , wherein the bisphosphonate is clodronate.
6. The method according to claim 1 , wherein the bone metastasis is osteolytic metastasis.
7. The method according to claim 1 , wherein the c-MAF expression level is quantified by means of a quantitative polymerase chain reaction (PCR), a DNA array, or an RNA array.
8. The method according to claim 1 , wherein the elevated c-MAF expression level is at least about 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.
9. A method for the treatment of bone metastasis in a subject suffering ER+ breast cancer comprising:
(i) obtaining a primary breast cancer tumor tissue sample from the human subject;
(ii) quantifying c-MAF expression level in the primary breast cancer tumor tissue sample;
(iii) comparing the expression level obtained in (ii) with the expression level of the c-MAF gene in a control sample, wherein the control sample is a tumor tissue sample of breast cancer from a subject who has not suffered metastasis,
(iv) determining that said subject has an elevated c-MAF expression level compared to a control sample, wherein the c-MAF expression level is considered to be elevated when the expression level in the primary breast cancer tumor tissue sample is at least 5 times or greater than the control sample; and
(v) administering an agent capable of avoiding, treating, or preventing bone degradation to said subject suffering ER+ breast cancer after step (iv), and
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, wherein the quantification of the expression level comprises quantifying the messenger RNA (mRNA) of c-MAF, or a fragment of said mRNA, or quantifying the complementary DNA (cDNA) of c-MAF, or a fragment of said cDNA.
10. The method according to claim 9 , wherein the RANKL inhibitor is selected from the group consisting of: a RANKL specific antibody and osteoprotegerin.
11. The method according to claim 10 , wherein the RANKL specific antibody is denosumab.
12. The method according to claim 9 , wherein the bisphosphonate is zoledronic acid.
13. The method according to claim 9 , wherein the bisphosphonate is clodronate.
14. The method according to claim 9 , wherein the expression level is quantified by means of a quantitative polymerase chain reaction (PCR), a DNA array, or an RNA array.
15. The method according to claim 1 , wherein the estrogen receptor modulator inhibits the binding of estrogen to the estrogen receptor.
16. The method according to claim 1 , wherein the estrogen receptor modulator is selected from the group consisting of progestogen, estradiol, droloxifene, raloxifiene, lasofoxifene, TSE-424, tamoxifen, idoxifene, LY353381, LY117081, toremifene, fulvestrant, 4-[7-(2,2-dimethyl-1-oxopropoxy-4-methyl-2-[4-[2-(1-piperidinyl) ethoxy]phenyl]-2H-1-benzopyran-3-yl]-phenyl-2,2-dimethyl propanoate, and SH646.
17. The method according to claim 9 , wherein the estrogen receptor modulator inhibits the binding of estrogen to the estrogen receptor.
18. The method according to claim 9 , wherein the estrogen receptor modulator is selected from the group consisting of progestogen, estradiol, droloxifene, raloxifiene, lasofoxifene, TSE-424, tamoxifen, idoxifene, LY353381, LY117081, toremifene, fulvestrant, 4-[7-(2,2-dimethyl-1-oxopropoxy-4-methyl-2-[4-[2-(1-piperidinyl) ethoxy]phenyl]-2H-1-benzopyran-3-yl]-phenyl-2,2-dimethyl propanoate, and SH646.
19. The method according to claim 1 , wherein the method does not involve determining the expression level of any additional marker.
20. The method according to claim 9 , wherein the method does not involve determining the expression level of any additional marker.
Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Feb 13, 2025
From: GOMIS, ROGER
To: FUNDACIÓ PRIVADA INSTITUT DE RECERCA BIOMÈDICA; FUNDACIÓ PRIVADA INSTITUCIÓ CATALANA DE RECERCA I ESTUDIS AVANÇATS
Reel/Frame 070234/0607 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Feb 13, 2025
From: PAVLOVIC, MILICA; ARNAL, ANNA; TARRAGONA, MARIA
To: FUNDACIÓ PRIVADA INSTITUT DE RECERCA BIOMÈDICA
Reel/Frame 070234/0611 →
CHANGE OF NAME
Recorded Feb 13, 2025
From: FUNDACIÓ PRIVADA INSTITUCIÓ CATALANA DE RECERCA I ESTUDIS AVANÇATS; FUNDACIÓ PRIVADA INSTITUT DE RECERCA BIOMÈDICA
To: INSTITUCIÓ CATALANA DE RECERCA I ESTUDIS AVANÇATS; FUNDACIÓ INSTITUT DE RECERCA BIOMÈDICA (IRB BARCELONA)
Reel/Frame 070234/0794 →
Priority Claims (2)
ES ES201031478
· Oct 6, 2010
· national
ES ES201131073
· Jun 27, 2011
· national
Continuity (3)
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