IP Library Granted Patent US 10,329,624
Granted Patent B2
US 10,329,624 · App. 15/130,777 · Granted Jun 25, 2019

Grading of breast cancer

Inventors: Xiao-Jun Ma (San Diego, CA); Dennis C. Sgroi (Winchester, MA); Mark G. Erlander (Carlsbad, CA)
Assignees: Biotheranostics, Inc.; The General Hospital Corporation
C12Q1/6886A61K31/138G01N33/57415G01N33/57496C12Q2600/112C12Q2600/158C12Q2600/16
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Quick Facts
Patent No.
US 10,329,624
App. No.
15/130,777
Granted
Jun 25, 2019
Kind
B2
Abstract

Methods and compositions for the identification of breast cancer grade signatures are provided. The signature profiles are identified based upon multiple sampling of reference breast tissue samples from independent cases of breast cancer and provide a reliable set of molecular criteria for identification of cells as being in one or more particular stages and/or grades of breast cancer.

Claims (22)

1. A method of treating breast cancer in a human subject, said method comprising

assaying a sample from the human subject for gene expression levels of CENPA (centromere protein A (17 kD), chromosomal location 2p24-p21), RACGAP1 (Rac GTPase activating protein 1, chromosomal location 12p13.2-p13.1), RRM2 (ribonucleotide reductase M2 polypeptide, chromosomal location 2p25-p24), and NEK2 (NIMA (never in mitosis gene a)-related kinase, chromosomal location 1q32.2-q41);

determining a measure of similarity between the gene expression levels of the human subject and reference gene expression levels for a reference population of cancer subjects; and

either (a) treating the human subject with an antitumor agent, chemotherapy, or surgical removal of cancer tissue if the measure of similarity is above a threshold; or (b) conducting a cytological examination of cells from the human subject if the measure of similarity is above the threshold.

2. The method of claim 1 wherein said assaying comprises amplifying RNA from said sample.

3. The method of claim 2 wherein amplifying said RNA comprises quantitative PCR amplification.

4. The method of claim 2 wherein amplifying said RNA comprises reverse transcription PCR (RT-PCR).

5. The method of claim 1 wherein said assaying comprises determining gene expression levels by array hybridization.

6. The method of claim 1 wherein said sample is a ductal lavage, needle biopsy, surgical biopsy, or fine needle aspirate sample.

7. The method of claim 1 , wherein said sample is microdissected to isolate one or more cells suspected of being breast cancer cells and said assaying is of RNA in said isolated cells.

8. A method of treating breast cancer in a human subject, said method comprising

assaying a sample from the human subject for gene expression levels of CENPA (centromere protein A (17 kD), chromosomal location 2p24-p21), RACGAP1 (Rac GTPase activating protein 1, chromosomal location 12p13.2-p13.1), RRM2 (ribonucleotide reductase M2 polypeptide, chromosomal location 2p25-p24), and NEK2 (NIMA (never in mitosis gene a)-related kinase, chromosomal location 1q32.2-q41);

comparing the gene expression levels of the human subject to corresponding reference gene expression levels for a reference population of cancer subjects; and

either (a) treating the human subject with chemotherapy if the gene expression levels of the human subject are higher than the corresponding reference gene expression levels, (b) conducting a cytological examination of cells from the human subject if the gene expression levels of the human subject are higher than the corresponding reference gene expression levels, or (c) administering a breast cancer treatment other than chemotherapy if the gene expression levels of the human subject are lower than the corresponding reference gene expression levels.

9. The method of claim 8 wherein said assaying comprises amplifying RNA from said sample.

10. The method of claim 9 wherein amplifying said RNA comprises quantitative PCR amplification.

11. The method of claim 9 wherein amplifying said RNA comprises reverse transcription PCR (RT-PCR).

12. The method of claim 8 wherein said assaying comprises determining gene expression levels by array hybridization.

13. The method of claim 8 wherein said sample is a ductal lavage, needle biopsy, surgical biopsy, or fine needle aspirate sample.

14. The method of claim 8 wherein said sample is microdissected to isolate one or more cells suspected of being breast cancer cells and said assaying is of RNA in said isolated cells.

15. The method of claim 1 , wherein the human subject is treated with chemotherapy if the measure of similarity is above the threshold.

16. The method of claim 8 , wherein the human subject is treated with chemotherapy if the gene expression levels of the human subject are higher than the corresponding reference gene expression levels.

Assignments (4)
RELEASE OF SECURITY INTEREST RECORDED AT REEL/FRAME 055818/0519 Recorded Apr 24, 2026
From: BANK OF AMERICA, N.A., AS COLLATERAL AGENT
To: BIOTHERANOSTICS, INC.
Reel/Frame 075457/0572 →
SECURITY INTEREST Recorded Apr 5, 2021
From: BIOTHERANOSTICS, INC.
To: BANK OF AMERICA, N.A., AS COLLATERAL AGENT
Reel/Frame 055818/0519 →
RELEASE OF SECURITY INTEREST Recorded Feb 22, 2021
From: INNOVATUS LIFE SCIENCES LENDING FUND I, LP
To: BIOTHERANOSTICS, INC.
Reel/Frame 055357/0691 →
SECURITY INTEREST Recorded Apr 22, 2019
From: BIOTHERANOSTICS, INC.
To: INNOVATUS LIFE SCIENCES LENDING FUND I, LP
Reel/Frame 048960/0213 →
Continuity (5)
Continuation 13083500 · Apr 8, 2011
Continuation 11946835 · Nov 28, 2007
Continuation 10211015 · Aug 1, 2002
Continuation In Part 10028018 · Dec 21, 2001
Related Publication 20170073767A1 · Mar 16, 2017