Predicting outcome with tamoxifen in breast cancer
First Claim
1. A method to determine the risk of cancer recurrence in a human subject afflicted with ER+ (estrogen receptor positive) breast cancer, said method comprisingdetermining an expected cancer recurrence for said subject by assaying a sample of breast cancer cells from said subject for a ratio of HoxB13 and IL17BR RNA expression levels that is higher than the mean (average) ratio of HoxB13 and IL17BR RNA expression levels in ER+ breast cancer cells;
- ordetermining an expected lack of cancer recurrence for said subject by assaying a sample of breast cancer cells from said subject for a ratio of HoxB13 and IL17BR RNA expression levels that is below the mean (average) ratio of HoxB13 and IL17BR RNA expression levels in ER+ breast cancer cells;
wherein said mean (average) ratio of HoxB13 and IL17BR RNA expression levels is determined from the mean (average) of HoxB13 RNA expression levels, and the mean (average) of IL17BR RNA expression levels, in ER+ breast cancer cell samples from human breast cancer subjects that respond to treatment with tamoxifen and human breast cancer subjects that do not respond to treatment with tamoxifen.
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Accused Products
Abstract
Methods and compositions are provided for the identification of expression signatures in ER+ breast cancer cases, where the signatures correlate with responsiveness, or lack thereof, to tamoxifen treatment. The signature profiles are identified based upon sampling of reference breast tissue samples from independent cases of breast cancer and provide a reliable set of molecular criteria for predicting the efficacy of treating a subject with ER+ breast cancer with tamoxifen. Additional methods and compositions are provided for predicting tamoxifen responsiveness in cases of ER+ breast cancer by use of three biomarkers. Two biomarkers display increased expression correlated with tamoxifen response while the third biomarker displays decreased expression correlated with tamoxifen response.
76 Citations
43 Claims
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1. A method to determine the risk of cancer recurrence in a human subject afflicted with ER+ (estrogen receptor positive) breast cancer, said method comprising
determining an expected cancer recurrence for said subject by assaying a sample of breast cancer cells from said subject for a ratio of HoxB13 and IL17BR RNA expression levels that is higher than the mean (average) ratio of HoxB13 and IL17BR RNA expression levels in ER+ breast cancer cells; - or
determining an expected lack of cancer recurrence for said subject by assaying a sample of breast cancer cells from said subject for a ratio of HoxB13 and IL17BR RNA expression levels that is below the mean (average) ratio of HoxB13 and IL17BR RNA expression levels in ER+ breast cancer cells; wherein said mean (average) ratio of HoxB13 and IL17BR RNA expression levels is determined from the mean (average) of HoxB13 RNA expression levels, and the mean (average) of IL17BR RNA expression levels, in ER+ breast cancer cell samples from human breast cancer subjects that respond to treatment with tamoxifen and human breast cancer subjects that do not respond to treatment with tamoxifen. - View Dependent Claims (5, 6, 7, 8, 9, 10, 11, 12, 38)
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2. A method of determining the outcome of a human subject having ER+ (estrogen receptor positive) breast cancer, or of a subject afflicted with ER+ breast cancer, if said subject is treated with tamoxifen, said method comprising:
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assaying a breast cancer cell sample from said subject wherein a ratio of HoxB13 and IL17BR RNA expression levels that is below the mean (average) ratio of HoxB13 and IL17BR expression levels in ER+ breast cancer cells indicates a cancer-free outcome, and a ratio above the mean (average) ratio of HoxB13 and IL17BR RNA expression levels in ER+ breast cancer cells indicates an outcome comprising cancer recurrence; wherein said mean (average) ratio of HoxB13 and IL17BR RNA expression levels is determined from the mean (average) of HoxB13 RNA expression levels, and the mean (average) of IL17BR RNA expression levels, in ER+ breast cancer cell samples from human breast cancer subjects that respond to treatment with tamoxifen and human breast cancer subjects that do not respond to treatment with tamoxifen. - View Dependent Claims (13, 14, 15, 16, 17, 18, 19, 20, 39, 42, 43)
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3. A method to predict an expected lack of response to tamoxifen treatment in a human ER+ (estrogen receptor positive) breast cancer patient, said method comprising
determining an expected lack of response to tamoxifen treatment for said patient by assaying a sample of breast cancer cells from said patient for a ratio of HoxB13 and IL17BR expression levels that is higher than the mean (average) ratio of HoxB13 and IL17BR expression levels in ER+ breast cancer cells; wherein said mean (average) ratio of HoxB13 and IL17BR RNA expression levels is determined from the mean (average) of HoxB13 RNA expression levels, and the mean (average) of IL17BR RNA expression levels, in ER+ breast cancer cell samples from human breast cancer subjects that respond to treatment with tamoxifen and human breast cancer subjects that do not respond to treatment with tamoxifen. - View Dependent Claims (21, 22, 23, 24, 25, 26, 27, 28, 40)
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4. A method to determine risk of cancer recurrence in a human subject having ER+ (estrogen receptor positive) breast cancer if treated with tamoxifen, said method comprising
assaying a sample of breast cells from said subject for increased expression of human HOXB 13 sequences, or decreased expression of IL17BR sequences, relative to the mean (average) expression thereof in ER+ breast cancer cell samples from human breast cancer subjects that respond to treatment with tamoxifen and human breast cancer subjects that do not respond to treatment with tamoxifen, as an indicator of tamoxifen non-responsiveness; - or
decreased expression of human HOXB 13 sequences, or increased expression of IL17BR sequences, relative to the mean (average) expression thereof in ER+ breast cancer cell samples from human breast cancer subjects that respond to treatment with tamoxifen and human breast cancer subjects that do not respond to treatment with tamoxifen, as an indicator of tamoxifen responsiveness. - View Dependent Claims (29, 30, 31, 32, 33, 34, 35, 36, 37, 41)
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Specification