IP Library Granted Patent US 7,056,663
Granted Patent B2
US 7,056,663 · App. 09/816,460 · Granted Jun 6, 2006

Prognostic methods for breast cancer

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Quick Facts
Patent No.
US 7,056,663
App. No.
09/816,460
Granted
Jun 6, 2006
Kind
B2
Abstract

Methods of determining the likelihood of the re-occurrence of tumors and of determining the aggressiveness of post-surgical treatment are provided which rely on analysis of a loss of heterogeneity at the particular chromosomal locus 3p24.3. Loss of expression or hypermethylation of the thyroid hormone receptor β1 gene is also predictive of an increased re-occurrence of tumors.

Claims (38)

1. A method for determining the likelihood of tumor reoccurrence in a patient previously diagnosed with a breast tumor, said method comprising:

(1) providing a target cell sample from said patient, wherein said target cell sample comprises morphologically normal breast cells associated with the tumor, and wherein said target sample comprises a standardized volume to cell ratio, wherein the cells in said target sample are counted prior to microdissection and solubilization;

(2) analyzing the target cell sample for loss of heterozygosity (LOH) at chromosomal locus 3p24.3;

(3) classifying samples having LOH at chromosomal locus 3p24.3 as positive, wherein a positive sample indicates greater likelihood of tumor reoccurrence; and

(4) identifying said positive sample to a clinician for prognosing and determining the course of treatment for said patient.

2. The method of claim 1 , wherein the breast tumor cells have previously been determined to have LOH at 3p24.3.

3. The method of claim 1 , wherein said patient has undergone a surgical procedure to treat said previously diagnosed breast tumor.

4. A method of determining post-surgical treatment for a breast cancer patient, said method comprising:

(1) providing a target cell sample from said patient, wherein said target cell sample comprises morphologically normal breast cells associated with the breast cancer cells, and wherein said target sample comprises a standardized volume to cell ratio, wherein the cells in said target sample are counted prior to microdissection and solubilization;

(2) analyzing the target cell sample for loss of heterozygosity (LOH) at chromosomal locus 3p24.3;

(3) classifying samples having LOH at chromosomal locus 3p24.3 as positive, wherein a positive sample is an indicator that more aggressive post-surgical treatment is required; and

(4) identifying said positive sample to a clinician for determining post-surgical treatment for said breast cancer patient.

5. The method of claim 4 , wherein the breast tumor cells have previously been determined to have LOH at 3p24.3.

6. A method of identifying a patient as being at risk for breast cancer, said method comprising:

(1) obtaining a breast tissue cell sample from said patient, wherein said breast tissue cell sample comprises a standardized volume to cell ratio, wherein the cells in said target sample are counted prior to microdissection and solubilization;

(2) analyzing the breast tissue cell sample for loss of heterozygosity (LOH) at chromosomal locus 3p24.3;

(3) classifying patients whose breast tissue cell sample exhibit LOH at chromosomal locus 3p24.3 as at risk of breast cancer; and

(4) identifying said breast tissue cell sample exhibiting LOH to a clinician for prognosing and determining the course of treatment for said patient.

7. The method of claim 6 , wherein said breast tissue cell sample is selected from the group consisting of nipple aspirate fluid, ductal lavage fluid, and breast tissue biopsy tissue.

8. A method for determining the likelihood of tumor re-occurrence in a patient previously diagnosed with a breast tumor, said method comprising:

(1) providing a target cell sample from said patient, wherein said target cell sample comprises morphologically normal cells from tissue peripheral to the carcinoma cells;

(2) analyzing the target cell sample for the level of expression of thyroid hormone receptor β1 compared to a control cell sample; and

(3) classifying a target cell sample having a lower level of expression of thyroid hormone receptor β1 compared to the control cell sample as positive, wherein a positive sample indicates greater likelihood of tumor re-occurrence.

9. The method of claim 8 , wherein the level of expression of thyroid hormone receptor β1 is determined by analyzing the amount of mRNA for thyroid hormone receptor β1.

10. The method of claim 8 , wherein the level of expression of thyroid hormone receptor β1 is determined by analyzing the amount of thyroid hormone receptor β1 protein.

11. A method of determining post-surgical treatment for a breast cancer patient, said method comprising:

(1) providing a target cell sample from said patient, wherein said target cell sample comprises morphologically normal cells from tissue peripheral to the carcinoma cells;

(2) analyzing the target cell sample for the level of expression of thyroid hormone receptor β1 compared to a control cell sample; and

(3) classifying a target cell sample having a lower level of expression of thyroid hormone receptor β1 compared to a control cell sample as positive, wherein a positive sample is an indicator that more aggressive post-surgical treatment is required.

12. The method of claim 11 , wherein the level of expression of thyroid hormone receptor β1 is determined by analyzing the amount of mRNA for thyroid hormone receptor β1.

13. The method of claim 11 , wherein the level of expression of thyroid hormone receptor β1 is determined by analyzing the amount of thyroid hormone receptor β1 protein.

14. A method of identifying a patient as at risk for breast cancer, said method comprising:

(1) obtaining a breast tissue cell sample from said patient;

(2) analyzing the breast tissue sample for the level of expression of thyroid hormone receptor β1 compared to a control cell sample; and

(3) classifying a patient whose breast tissue cell samples have a lower level of expression of thyroid hormone receptor β1 compared to a control cell sample as at risk for breast cancer.

15. The method of claim 14 , wherein said breast tissue cell sample is selected from the group consisting of nipple aspirate fluid, ductal lavage fluid, said breast tissue biopsy tissue.

16. The method of claim 14 , wherein the level of expression of thyroid hormone receptor β1 is determined by analyzing the amount of thyroid hormone receptor β1 protein.

17. The method of claim 14 , wherein the level of expression of thyroid hormone receptor β1 is determined by analyzing the amount of thyroid hormone receptor β1 protein.

Assignments (3)
CORRECTIVE ASSIGNMENT TO CORRECT THE ASSIGNEE'S ADDRESS FROM 475 BRANNAN STREET, SUITE 200, SAN FRANCISCO, CA 94107 PREVIOUSLY RECORDED ON REEL 023180 FRAME 0332. ASSIGNOR(S) HEREBY CONFIRMS THE CORRECT ASSIGNEE'S ADDRESS TO BE 475 BRANNAN STREET, SUITE 220, SAN FRANCISCO, CA 94107. Recorded Dec 29, 2009
From: CALIFORNIA PACIFIC MEDICAL CENTER
To: SUTTER WEST BAY HOSPITALS, DBA CALIFORNIA PACIFIC MEDICAL CENTER
Reel/Frame 023715/0749 →
CHANGE OF NAME Recorded Sep 2, 2009
From: CALIFORNIA PACIFIC MEDICAL CENTER
To: SUTTER WEST BAY HOSPITALS, DBA CALIFORNIA PACIFIC MEDICAL CENTER
Reel/Frame 023180/0332 →
CONFIRMATORY LICENSE Recorded Jul 7, 2008
From: CALIFORNIA PACIFIC MEDICAL CTR RES INST
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 021194/0608 →