Predicting breast cancer treatment outcome
View Patent ↗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 treatment with tamoxifen or another antiestrogen agent against breast cancer 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 breast cancer with tamoxifen or another antiestrogen agent against breast cancer. Additional methods and compositions are provided for predicting responsiveness to tamoxifen or another antiestrogen agent against breast cancer in cases of 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.
1. A method for treating a human subject having ER+ (estrogen receptor positive) breast cancer, comprising
assaying a breast cancer cell sample from the human subject by determining a ratio of HoxB13 and IL17BR mRNA expression levels in the breast cancer cell sample;
comparing the ratio of HoxB13 and IL17BR mRNA expression levels in the breast cancer cell sample to a HoxB13 and IL17BR mRNA expression level threshold ratio,
wherein a ratio of HoxB13 and IL17BR mRNA expression levels above the threshold ratio indicates an outcome comprising cancer recurrence via metastasis following tamoxifen or letrozole treatment, and
treating the human subject with an alternative therapy other than tamoxifen or letrozole, if the ratio of HoxB13 and IL17BR mRNA expression levels is above the threshold ratio, wherein the alternative therapy other than tamoxifen or letrozole comprises a selective estrogen receptor modulator (SERM), a selective estrogen receptor downregulator (SERD), an aromatase inhibitor (AI), surgical ovarian ablation, or chemical ovarian ablation.
2. The method of claim 1 , wherein said mRNA expression levels are determined by quantitative PCR.
3. The method of claim 1 , wherein said assaying comprises RT-PCR (reverse transcription polymerase chain reaction).
4. The method of claim 3 , wherein the ratio of HoxB13 and IL17BR mRNA expression levels is expressed as ACT, wherein CT is the PCR amplification cycle in which the HoxB13 or IL17BR mRNA reaches a threshold amount, and wherein ACT is the CT difference between HoxB13 or IL17BR mRNA.
5. The method of claim 1 , wherein said breast cancer cell sample is a formalin fixed paraffin embedded (FFPE), ductal lavage or fine needle aspiration sample.
6. The method of claim 1 , wherein said breast cancer cell sample is a section of tissue from a subject or comprises cells microdissected from said section.
7. The method of claim 1 , wherein the alternative therapy other than tamoxifen or letrozole comprises a selective estrogen receptor modulator (SERM), a selective estrogen receptor downregulator (SERD), or an aromatase inhibitor (AI).
8. The method of claim 1 , wherein the alternative therapy other than tamoxifen or letrozole comprises anastrozole, vorozole, exemestane, androstenedione, or formestane.
9. The method of claim 1 , wherein the alternative therapy other than tamoxifen or letrozole comprises surgical or chemical ovarian ablation.