GENE EXPRESSION MARKERS OF RECURRENCE RISK IN CANCER PATIENTS AFTER CHEMOTHERAPY

1 . A method of predicting the clinical outcome for a patient receiving adjuvant anthracycline-based chemotherapy and having hormone receptor positive (HR+) breast cancer, the method comprising:

assaying an expression level of at least one RNA transcript listed in Tables 4A-B, or its expression product, in a biological sample comprising cancer cells obtained from the patient; and

determining a normalized expression level of the at least one RNA transcript, or its expression product,

wherein the normalized expression level of the at least one RNA transcript listed in Table 4A, or its expression product, correlates with a decreased likelihood of a positive clinical outcome; and

wherein the normalized expression level of the at least one RNA transcript listed in Table 4B, or its expression product, correlates with an increased likelihood of a positive clinical outcome.

2 . The method of claim 1 , wherein the patient is human.

3 . The method of claim 1 , wherein the expression level is obtained by gene expression profiling.

4 . The method of claim 3 , wherein gene expression profiling comprises a reverse transcription-polymerase chain reaction (RT-PCR)-based method.

5 . The method of claim 3 , wherein gene expression profiling comprises digital gene expression.

6 . The method of claim 1 , further comprising creating a report based on the normalized expression level.

7 . The method of claim 6 , wherein, if the patient has a decreased likelihood of a positive clinical outcome, the report provides information to support a decision to use an adjuvant treatment.

8 . The method of claim 7 , wherein the adjuvant treatment is at least one from the list consisting of a non-anthracycline chemotherapy and a radiation therapy.

9 . A method of predicting the clinical outcome for a patient receiving adjuvant anthracycline-based chemotherapy and having hormone receptor negative (HR−) breast cancer, the method comprising:

assaying an expression level of at least one RNA transcript listed in Tables 5A-B, or its expression product, in a biological sample comprising cancer cells obtained from the patient; and

determining a normalized expression level of the at least one RNA transcript, or its expression product,

wherein the normalized expression level of the at least one RNA transcript listed in Table 5A, or its expression product, correlates with a decreased likelihood of a positive clinical outcome; and

wherein the normalized expression level of the at least one RNA transcript listed in Table 5B, or its expression product, correlates with an increased likelihood of a positive clinical outcome.

10 . The method of claim 9 , wherein the patient is human.

11 . The method of claim 9 , wherein the expression level is obtained by gene expression profiling.

12 . The method of claim 11 , wherein gene expression profiling comprises a reverse transcription-polymerase chain reaction (RT-PCR)-based method.

13 . The method of claim 11 , wherein gene expression profiling comprises digital gene expression.

14 . The method of claim 9 , further comprising creating a report summarizing the normalized expression level.

15 . The method of claim 14 , wherein, if the patient has a decreased likelihood of a positive clinical outcome, the report provides information to support a decision to use an adjuvant treatment.

16 . The method of claim 15 , wherein the adjuvant treatment is at least one from the list consisting of a non-anthracycline chemotherapy and a radiation therapy.

17 . A method of predicting the clinical outcome for a patient receiving adjuvant anthracycline-based chemotherapy and having hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2−) breast cancer, the method comprising:

assaying an expression level of the at least one RNA transcript listed in Tables 6A-B, or its expression product, in a biological sample comprising cancer cells obtained from the patient; and

determining a normalized expression level of the at least one RNA transcript, or its expression product,

wherein the normalized expression level of the at least one RNA transcript listed in Table 6A, or its expression product, correlates with a decreased likelihood of a positive clinical outcome; and

wherein the normalized expression level of the at least one RNA transcript listed in Table 6B, or its expression product, correlates with an increased likelihood of a positive clinical outcome.

18 . The method of claim 17 , further comprising creating a report summarizing the normalized expression level.

19 . The method of claim 18 , wherein, if the patient has a decreased likelihood of a positive clinical outcome, the report contains information to support the use of at least one adjuvant treatment from the list consisting of a non-anthracycline chemotherapy and a radiation therapy.

20 . A method of predicting the clinical outcome for a patient receiving adjuvant anthracycline-based chemotherapy and having hormone receptor negative (HR), human epidermal growth factor receptor 2 negative (HER2−) breast cancer, the method comprising:

assaying an expression level of at least one RNA transcript listed in Tables 7A-B, or its expression product, in a biological sample comprising cancer cells obtained from the patient; and

determining a normalized expression level of the at least one RNA transcript, or its expression product,

wherein the normalized expression level of the at least one RNA transcript listed in Table 7A, or its expression product, correlates with a decreased likelihood of a positive clinical outcome; and

wherein the normalized expression level of the at least one RNA transcript listed in Table 7B, or its expression product, correlates with an increased likelihood of a positive clinical outcome.

21 . The method of claim 20 , further comprising creating a report summarizing the normalized expression level.

22 . The method of claim 21 , wherein, if the patient has a decreased likelihood of a positive clinical outcome, the report provides information to support a decision to use at least one adjuvant treatment from the list consisting of a non-anthracycline chemotherapy and a radiation therapy.

23 . A method of predicting the clinical outcome for a patient receiving adjuvant anthracycline-based chemotherapy and having hormone receptor positive (HR+), human epidermal growth factor receptor 2 positive (HER2+) breast cancer, the method comprising:

assaying an expression level of at least one RNA transcript listed in Tables 8A-B, or its expression product, in a biological sample comprising cancer cells obtained from the patient; and

determining a normalized expression level of the at least one RNA transcript, or its expression product,

wherein the normalized expression level of the at least one RNA transcript listed in Table 8A, or its expression product, correlates with a decreased likelihood of a positive clinical outcome; and

wherein the normalized expression level of the at least one RNA transcript listed in Table 8B, or its expression product, correlates with an increased likelihood of a positive clinical outcome.

24 . The method of claim 23 , wherein the patient is human.

25 . The method of claim 23 , further comprising creating a report summarizing the normalized expression level.

26 . The method of claim 25 , wherein, if the patient has a decreased likelihood of a positive clinical outcome, the report provides information to support a decision to use at least one adjuvant treatment from the list consisting of a non-anthracycline chemotherapy and radiation therapy.

27 . A method of predicting the clinical outcome for a patient receiving adjuvant anthracycline-based chemotherapy and having hormone receptor negative (HR−), human epidermal growth factor receptor 2 positive (HER2+) breast cancer, the method comprising:

assaying an expression level of at least one RNA transcript listed in Tables 9A-B, or its expression product, in a biological sample comprising cancer cells obtained from the patient; and

determining a normalized expression level of the at least one RNA transcript, or its expression product,

wherein the normalized expression level of the at least one RNA transcript listed in Table 9A, or its expression product, correlates with a decreased likelihood of a positive clinical outcome; and

wherein the normalized expression level of the at least one RNA transcript listed in Table 9B, or its expression product, correlates with an increased likelihood of a positive clinical outcome.

28 . The method of claim 27 , wherein the patient is human.

29 . The method of claim 27 , further comprising creating a report summarizing the normalized expression level.

30 . The method of claim 29 , wherein, if the patient has a decreased likelihood of a positive clinical outcome, the report provides information to support a decision to use at least one adjuvant treatment from the list consisting of a non-anthracycline chemotherapy and a radiation therapy.

31 . A method of predicting the likelihood that a patient having hormone receptor positive (HR+) breast cancer will exhibit a clinical benefit in response to adjuvant treatment with an anthracycline-based chemotherapy, the method comprising:

assaying a biological sample obtained from a cancer tumor of the patient for an expression level of at least one RNA transcript listed in Tables 4A-B, 6A-B, and/or 8A-B, or its expression product,

determining a normalized expression level of the at least one RNA transcript in Tables 4A-B, 6A-B, and/or 8A-B, or its expression product,

wherein the normalized expression level of the at least one RNA transcript listed in Table 4A, 6A, and/or 8A, or its expression product, positively correlates with a clinical benefit in response to treatment with an anthracycline-based chemotherapy; and

wherein the normalized expression level of the at least one RNA transcript listed in Table 4B, 6B, and/or 8B, or its expression product, negatively correlates with a clinical benefit in response to treatment with an anthracycline-based chemotherapy.

32 . The method of claim 31 , further comprising: creating a report based on the normalized expression level, wherein the report provides information to support a treatment decision.

33 . A method of predicting the likelihood that a patient having hormone receptor negative (HR−) breast cancer will exhibit a clinical benefit in response to adjuvant treatment with an anthracycline-based chemotherapy, the method comprising:

assaying a biological sample obtained from a cancer tumor of the patient for an expression level of at least one RNA transcript listed in Tables 5A-B, 7A-B, and/or 9A-B, or its expression product,

determining a normalized expression level of the at least one RNA transcript in Tables 5A-B, 7A-B, and/or 9A-B, or its expression product,

wherein the normalized expression level of the at least one RNA transcript listed in Table 5A, 7A, and/or 9A, or its expression product, positively correlates with a clinical benefit in response to treatment with an anthracycline-based chemotherapy; and

wherein the normalized expression level of the at least one RNA transcript listed in Table 5B, 7B, and/or 9B, or its expression product, negatively correlates with a clinical benefit in response to treatment with an anthracycline-based chemotherapy.

34 . The method of claim 33 , further comprising: creating a report based on the normalized expression level, wherein the report provides information to support a treatment decision.

35 . A kit comprising a set of gene specific probes and/or primers for quantifying the expression of one or more of the genes listed in any one of Tables 1, 2, 3, 4A-B, 5A-B, 6A-B, 7A-B, 8A-B, and 9A-B by quantitative RT-PCR.

36 . The kit of claim 35 further comprising one or more reagents for expression of RNA from tumor samples.

37 . The kit of claim 35 or claim 36 comprising one or more containers.

38 . The kit of claim 35 or claim 36 comprising one or more algorithms that yield prognostic or predictive information.

39 . The kit of claim 38 wherein one or more of said containers comprise pre-fabricated microarrays, a buffers, nucleotide triphosphates, reverse transcriptase, DNA polymerase, RNA polymerase, probes, or primers.

40 . The kit of claim 38 comprising a label or package insert with instructions for use of its components.

41 . The kit of claim 40 wherein the instructions comprise directions for use in the prediction or prognosis of breast cancer.

42 . A method of preparing a personalized genomics profile for a patient comprising the steps of: (a) determining the normalized expression levels of the RNA transcripts or the expression products of one or more genes listed in Tables 1, 2, 3, 4A-B, 5A-B, 6A-B, 7A-B, 8A-B, and 9A-B, in a cancer cell obtained from said patient; and (b) creating a report summarizing the data obtained by said gene expression analysis.

43 . The method of claim 42 comprising communicating the report to the patient or a physician of the patient.