Post-treatment breast cancer prognosis

Abstract

The disclosure includes the identification and use of gene expression profiles, or patterns, with clinical relevance to extended treatment and cancer-free survival in a patient. In particular, the disclosure includes the identities of genes that are expressed in correlation with benefit in a switch in endocrine therapy used to treat a patient. The levels of gene expression are disclosed as a molecular index for predicting clinical outcome, and so prognosis, for the patient. The disclosure further includes methods for predicting cancer recurrence, and/or predicting occurrence of metastatic cancer, after initial treatment with an anti-estrogen agent. The disclosure further includes methods for determining or selecting the treatment of a subject based upon the likelihood of life expectancy, cancer recurrence, and/or cancer metastasis.

What is claimed is: 
     
         1 . A method comprising:
 preparing cDNA from nucleic acids in a sample of ER+ breast cancer cells from a breast cancer afflicted subject,   determining the expression level of the HoxB13 gene from said cDNA,   identifying the subject as having undergone removal of the breast cancer and as having been treated with a first endocrine therapy for a period of time without cancer recurrence, and   classifying the subject as expected to benefit from treatment with the same first endocrine therapy or a different second endocrine therapy after cessation of the first endocrine therapy, wherein said classifying is based upon an elevated expression level of HoxB13.   
     
     
         2 . A method comprising:
 preparing cDNA from nucleic acids in a sample of ER+ breast cancer cells from a breast cancer afflicted subject,   determining the expression levels of the seven genes in the disclosed Breast Cancer Index (BCI) from said cDNA, wherein said genes are HoxB13, IL17BR, Bub1B, CENPA, NEK2, RACGAP1, and RRM2, to determine a BCI value,   identifying the subject as having undergone removal of the breast cancer and as having been treated with endocrine therapy for a period of time without cancer recurrence, and   classifying the cancer as likely to recur due to a high risk BCI value.   
     
     
         3 . The method of  claim 1  wherein said nucleic acids are mRNA from said sample. 
     
     
         4 . The method of  claim 3  wherein said RNA is used for PCR (polymerase chain reaction). 
     
     
         5 . The method of  claim 1  wherein said determining comprises using an array. 
     
     
         6 . The method of  claim 1  wherein said sample is dissected from tissue removed from said subject. 
     
     
         7 . The method of  claim 4  wherein said PCR is RT-PCR (reverse transcription-PCR), optionally real time RT-PCR. 
     
     
         8 . The method of  claim 1  wherein said sample is a formalin fixed paraffin embedded (FFPE) sample. 
     
     
         9 . The method of  claim 1 , further comprising treating said subject with letrozole after cessation of tamoxifen treatment. 
     
     
         10 . The method of  claim 1  further comprising assaying for the H:I ratio in said sample and wherein said ratio is used to indicate an elevated expression level of HoxB13. 
     
     
         11 . The method of  claim 1  wherein said cancer is ductal carcinoma in situ (DCIS) and said cancer recurrence comprises local recurrence. 
     
     
         12 . The method of  claim 1  wherein the first endocrine therapy is treatment with tamoxifen and the second endocrine therapy is treatment with letrozole. 
     
     
         13 . A method to treat a cancer patient, said method comprising
 preparing cDNA from nucleic acids in a sample of ER+ breast cancer cells from a breast cancer afflicted subject,   determining the expression level of the HoxB13 gene from said cDNA,   identifying the subject as having undergone removal of the breast cancer and as having been treated with a first endocrine therapy for a period of time without cancer recurrence,   classifying the subject as expected to benefit from treatment with the same first endocrine therapy or a different second endocrine therapy after cessation of the first endocrine therapy, wherein said classifying is based upon an elevated expression level of HoxB13, and   treating the patient with the second endocrine therapy after ending treatment with the first endocrine therapy.   
     
     
         14 . The method of  claim 13 , further comprising assaying for the H:I ratio in said sample, wherein said ratio is used to indicate an elevated expression level of HoxB13. 
     
     
         15 . The method of  claim 13  wherein the first endocrine therapy is treatment with tamoxifen and the second endocrine therapy is treatment with letrozole.