Methods of prognosing early stage breast lesions

Patent metadata

Field	Value
Publication number	US-11791043-B2
Application number	US-201816644239-A
Country	US
Kind code	B2
Filing date	Sep 6, 2018
Priority date	Sep 6, 2017
Publication date	Oct 17, 2023
Grant date	Oct 17, 2023

Abstract

A method is provided for prognosing a risk in a patient diagnosed with a premalignant lesion of the breast of the lesion progressing to breast cancer, the method comprising: providing a tissue sample of the premalignant lesion; detecting one or more variants of Osteopontin (OPN) selected from OPN-a, OPN-b and OPN-c in the sample; and prognosing an elevated risk of the lesion progressing to breast cancer if OPN-b and/or OPN-c is detected and/or OPN-a is elevated above normal levels in the tissue sample. Methods of assessing risk of death from breast cancer, methods of treatment, and kits for prognosis are also provided herein.

First claim

The invention claimed is:

1. A method for prognosing an elevated risk in a patient diagnosed with a premalignant lesion of the breast, of the lesion progressing to breast cancer and treating the patient, the method comprising:
providing a sample of the premalignant lesion;
detecting one or more variants of Osteopontin (OPN) selected from OPN-a, OPN-b, and OPN-c in the sample, wherein detecting comprises immunohistochemically staining the sample and measuring one or more of stain intensity and percent positivity for each stain;
assigning a pathology score to the sample, the pathology score comprising 0, 1, 2, or 3 for stain intensity, or 0, 1, 2, or 3 for stain percent positivity;
dichotomizing the pathology score into low (L=0 or 1) or high (H=2 or 3);
assigning the premalignant lesion to a risk category based on lesion type, wherein sine neoplasmate and ductal hyperplasia lesions comprise a low risk category, flat epithelial atypia (FEA), papillomatosis intraductalis (PI), atypical ductal hyperplasia (ADH), and lobular carcinoma in situ (LCIS) comprise an intermediate risk category, and ductal carcinoma in situ (DCIS) comprises a high risk category;
prognosing an elevated risk of the lesion progressing to breast cancer when:
(a) OPN-c is detected, the sample having a pathology score of H and the lesion having a risk category of low, intermediate, or high; and/or
(b) OPN-a or OPN-b is detected, the sample having a pathology score of H and the lesion having a risk category of high; and

administering chemoprevention therapy or surgery to the patient prognosed with the elevated risk of the lesion progressing to breast cancer.

2. The method according to claim 1 , wherein the sample is selected from a nucleic sample, a cytoplasmic sample, or both.

3. The method according to claim 2 , wherein immunohistochemically staining comprises contacting the sample with at least one antibody selective for one or more variants of OPN.

4. The method according to claim 3 , wherein at least one antibody selectively stains OPN-c (anti-OPN-c), and at least one antibody selectively stains OPN-a and/or OPN-b (anti-OPN-a/b).

5. The method according to claim 4 , wherein the antibody selective for OPN-c selectively binds an epitope comprising the sequence SEEKQNAVS (SEQ ID NO: 7) or a variant thereof, and/or the antibody selective for OPN-a/b binds an epitope comprising the sequence LYNKYPDAVATWLNPDPSQKQNLLAPN (SEQ ID NO: 8) or a variant thereof.

6. The method according to claim 5 , wherein the antibody comprises IgY AhOPNc or LF161.

7. The method according to claim 1 wherein the step of prognosing comprises subjecting a staining intensity or percent positivity of an immunohistochemistry stain for OPN-a/b and OPN-c, and risk category to a logistic regression to thereby determine risk for breast cancer or for death from breast cancer.

8. The method according to claim 1 , wherein chemoprevention therapy is selected from one or both of administering at least one estrogen receptor modulator and radiation.

9. The method according to claim 8 , wherein the estrogen receptor modulator is selected from raloxifene and tamoxifen.

10. A method of assessing an elevated risk of death from breast cancer in a patient diagnosed with a premalignant lesion of the breast and treating the patient, the method comprising:
providing a sample of the premalignant lesion;
immunohistochemically detecting OPN-a, OPN-b and/or OPN-c in the sample by detecting selective anti-OPN-c and anti-OPN-a/b stains and measuring one or more of intensity and percent positivity for each stain;
assigning a pathology score for each stain, comprising scoring the stains 0, 1, 2, or 3 for intensity and 0, 1, 2, or 3 for percent positivity and classifying the pathology score for each stain as high (H=2 or 3), low (L=0 or 1), or intermediate (I=one L and one H);
assigning the premalignant lesion to a risk category based on lesion type, wherein sine neoplasmate and ductal hyperplasia lesions comprise a low risk category, flat epithelial atypia (FEA), papillomatosis intraductalis (PI), atypical ductal hyperplasia (ADH), and lobular carcinoma in situ (LCIS) comprise an intermediate risk category, and ductal carcinoma in situ (DCIS) comprises a high risk category;
assessing the risk of death as elevated when:
(a) OPN-c is detected, the sample having a pathology score of H or I and the lesion having a risk category of high, intermediate, or low; or
(b) OPN-a/b is detected, the sample having a pathology score of H and the lesion having a risk category of high or intermediate, or
(c) OPN-a/b is detected, the sample having a pathology score of H or I and the lesion having a risk category of high; and

administering chemoprevention therapy or surgery to the patient assessed with the elevated risk of death from breast cancer.

11. The method according to claim 10 , further comprising assessing the risk of death as elevated when OPN-a/b is detected with a pathology score of H.

12. The method according to claim 10 , further comprising assessing the risk of death as elevated when OPN-c is detected with a pathology score of H.

13. The method according to claim 10 , wherein chemoprevention therapy is selected from one or both of administering at least one estrogen receptor modulator and radiation.

14. The method according to claim 13 , wherein chemoprevention therapy is selected from one or both of administering at least one estrogen receptor modulator and radiation.

Assignees

• Univ Cincinnati

Inventors

• Weber Georg F

Classifications

• G01N33/575

  for cancer · CPC title

• G01N33/57515

  of the breast · CPC title

• G16H50/20 Primary

  for computer-aided diagnosis, e.g. based on medical expert systems · CPC title

• G01N2333/52

  Assays involving cytokines · CPC title

• G01N2800/50

  Determining the risk of developing a disease · CPC title