Breast cancer biomarker signatures for invasiveness and prognosis

1. A method of diagnosing whether a subject has breast invasive ductal carcinoma (IDC) as compared to ductal carcinoma in situ (DCIS), comprising:

a) reverse transcribing RNA from a test sample obtained from the subject to provide a set of target oligodeoxynucleotides wherein the subject has breast IDC;

b) hybridizing the target oligodeoxynucleotides to a microarray comprising miR-210, let-7d and miR-221 specific probe oligonucleotides to provide a hybridization profile for the test sample; and

c) comparing the test sample hybridization profile to a hybridization profile generated from a control sample, wherein an increase in the expression of miR-210, let-7d and miR-221 is indicative of the subject having IDC as compared to ductal carcinoma in situ (DCIS).

2. The method of claim 1 , wherein step c) comprises comparing the test sample hybridization profile to a database, statistics, or table of miR levels associated with non-cancerous samples.

3. The method of claim 1 , wherein a level of expression of miR-210, let-7d and miR-221 is assessed by detecting the presence of a transcribed polynucleotide or portion thereof, wherein the transcribed polynucleotide comprises a coding region of miR-210, let-7d and miR-221.

4. The method of claim 1 , wherein the sample comprises cells obtained from the subject taken over time.

5. A method of determining disease progression of breast invasive ductal carcinoma (IDC) in a subject as compared to ductal carcinoma in situ (DCIS), comprising:

a) identifying the relative miR-210 expression compared to a control by:

i) extracting a test sample of tissue from a human subject, wherein the extracting is by hypodermic needle, microdissection, or laser capture; and

ii) measuring by microarray analysis the level of a miRNA/mRNA signature in the test sample of tissue from the human subject, the miRNA/mRNA signature consisting of miR-210, let-7d and miR-221; and,

b) determining the disease progression as IDC in the subject if the subject has increased miR-210, let-7d and miR-221 expression compared to the control; or, determining no disease progression if the subject does not have increased miR-210, let-7d and miR-221 expression compared to the control.

6. A method of claim 5 , which further comprises designing a treatment plan based on the diagnosis.

7. A method of claim 5 , which further comprises administration of a treatment based on the diagnosis.

8. A method of claim 5 , which further comprises determining prognosis based on the diagnosis.

9. A method for determining the likelihood of breast cancer progression in a human subject having breast cancer, comprising:

a) determining the expression level of a signature of hsa-miR-210, hsa-let-7d and hsa-miR-221 in a sample containing breast cancer cells from the subject with breast cancer, by assaying by microarray analysis a nucleic acid sample obtained from the breast cancer cells to determine the expression level of the miRNA signature in the nucleic acid sample;

b) comparing the expression level from step a) to a standard miRNA expression level in a control sample, and

determining that the subject has a poor survival outcome, if there is an increase in the expression levels of miRNA signature in the nucleic acid sample, as compared to a control sample.

10. The method of claim 9 , wherein the control sample comprises tissue from a representative individual or pool of individuals with breast cancer wherein the breast cancer has not progressed.

11. The method of claim 9 , wherein the control sample comprises tissue from the subject taken at an earlier point in time, as compared to the time of determining the expression level of step a).

12. The method of claim 9 , wherein the standard miRNA expression level is from the representative pool of individuals and is a mean, median or other statistically manipulated or otherwise summarized or aggregated representative miRNA expression level for the miRNA level in the control tissues in the subject.

13. The method of claim 9 , wherein the expression level of one or more of: miR-10b, miR-126, miR-143, miR-218 and miR-335-5p, is also measured relative to the expression level in the control sample, and wherein a decreased expression level of one or more of: miR-10b, miR-126, miR-143, miR-218 and miR-335-5p correlates with a higher risk of progression.