1. Abstract P6-09-23: SETER/PR - A robust 18-gene predictor of sensitivity to endocrine therapy in metastatic breast cancer
- Author
-
Ravi Murthy, Ta King, Bruno Valentin Sinn, Rebekah Gould, DN Kwiatkowski, V. Valero, Christos Hatzis, C Fu, Rosanna Lau, T-H Tsai, and William Fraser Symmans
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Microarray ,medicine.diagnostic_test ,medicine.drug_class ,business.industry ,Cancer ,medicine.disease ,Metastatic breast cancer ,Metastasis ,Breast cancer ,Estrogen ,Internal medicine ,Biopsy ,medicine ,Biomarker (medicine) ,business - Abstract
Rationale: A robust index for gene expression related to activity of estrogen (ESR1) and progesterone (PGR) receptors could predict sensitivity to endocrine therapy in metastatic breast cancer. Methods: Transcripts correlated with ESR1 and PGR expression in 389 hormone receptor-positive breast cancer samples (Affymetrix U133A microarrays) were ranked for reliability according to their pre-analytical (intratumoral heterogeneity, biopsy type) and analytical reproducibility. Eighteen target and ten reference genes were selected and summarized as the SETER/PR index. The SETER/PR index was evaluated in a different set of 140 biopsies from distant metastases of hormone receptor-positive and HER2-negative (HR+/HER2-) breast cancer, and in additional pre-analytical and analytical sample cohorts. Thereafter, SETER/PR was translated to a customized format for application to formalin-fixed and paraffin-embedded (FFPE) sections. Results: Higher SETER/PR in a metastasis was associated with longer progression-free survival (PFS, 9 vs. 2 months) and overall survival (OS, 50 vs. 19 months) following endocrine therapy in the cohort with metastatic breast cancer (MBC) and relapsed disease (n=79), so a cut point was defined in that cohort. SETER/PR was also significantly associated with PFS after adjusting for PR status of the metastasis, presence of visceral metastases, number of previous relapse events, and clinical history of previous sensitivity to endocrine therapy (HR 0.485, 95%CI 0.265 – 0.889, p = 0.019). Technically, SETER/PR was highly reproducible under different pre-analytical and analytical conditions, including host organ contamination. The translated SETER/PR assay used a single 10 µm FFPE tissue section, did not require RNA purification, and represented the microarray results from matched fresh samples with excellent agreement (correlation = 0.980, n = 31). Conclusion: The SETER/PR index is a new biomarker to predict PFS and OS for patients with HR+/HER2- MBC who receive endocrine therapy. The assay is applicable to FFPE tissue sections from small biopsies of metastases. Additional independent (blinded) validation studies will be necessary to confirm these results.Rationale: A robust index for gene expression related to activity of estrogen (ESR1) and progesterone (PGR) receptors could predict sensitivity to endocrine therapy in metastatic breast cancer. Methods: Transcripts correlated with ESR1 and PGR expression in 389 hormone receptor-positive breast cancer samples (Affymetrix U133A microarrays) were ranked for reliability according to their pre-analytical (intratumoral heterogeneity, biopsy type) and analytical reproducibility. Eighteen target and ten reference genes were selected and summarized as the SETER/PR index. The SETER/PR index was evaluated in a different set of 140 biopsies from distant metastases of hormone receptor-positive and HER2-negative (HR+/HER2-) breast cancer, and in additional pre-analytical and analytical sample cohorts. Thereafter, SETER/PR was translated to a customized format for application to formalin-fixed and paraffin-embedded (FFPE) sections. Results: Higher SETER/PR in a metastasis was associated with longer progression-free survival (PFS, 9 vs. 2 months) and overall survival (OS, 50 vs. 19 months) following endocrine therapy in the cohort with metastatic breast cancer (MBC) and relapsed disease (n=79), so a cut point was defined in that cohort. SETER/PR was also significantly associated with PFS after adjusting for PR status of the metastasis, presence of visceral metastases, number of previous relapse events, and clinical history of previous sensitivity to endocrine therapy (HR 0.485, 95%CI 0.265 – 0.889, p = 0.019). Technically, SETER/PR was highly reproducible under different pre-analytical and analytical conditions, including host organ contamination. The translated SETER/PR assay used a single 10 µm FFPE tissue section, did not require RNA purification, and represented the microarray results from matched fresh samples with excellent agreement (correlation = 0.980, n = 31). Conclusion: The SETER/PR index is a new biomarker to predict PFS and OS for patients with HR+/HER2- MBC who receive endocrine therapy. The assay is applicable to FFPE tissue sections from small biopsies of metastases. Additional independent (blinded) validation studies will be necessary to confirm these results. Citation Format: Sinn BV, Tsai T-H, Lau R, Fu C, Gould R, Murthy R, King TA, Hatzis C, Kwiatkowski DN, Valero V, Symmans WF. SETER/PR - A robust 18-gene predictor of sensitivity to endocrine therapy in metastatic breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-09-23.
- Published
- 2017
- Full Text
- View/download PDF