Prognostic methods for breast cancer
View Patent ↗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.
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.