Prediction of Tamoxifen Benefit in Premenopausal Breast Cancer Patients Evaluated by Three Methods for Determination of Hormone Receptor Status

Abstract

Abstract Background Tamoxifen remains an important adjuvant treatment in premenopausal patients with hormone receptor-positive breast cancer. Thus, determination of hormone receptors is important. Here, we compare cytosol-based methods, immunohistochemistry (IHC), and gene expression (GEX) analysis for determining hormone receptor status in premenopausal breast cancer patients from a randomized tamoxifen trial, to determine if any method is superior at identifying patients that benefit from tamoxifen. Methods Premenopausal patients (n = 564) were randomized to two years of tamoxifen or no systemic treatment. Estrogen receptor (ER) and progesterone receptor (PR) status by protein expression measured by cytosol-based methods and IHC, and mRNA by GEX analysis were compared in 313 patients with available data from all methods. Kaplan Meier estimates and Cox regression were used to evaluate the treatment-predictive value for recurrence-free interval (RFi) and overall survival (OS). Median follow-up for event-free patients was 26 (RFi) and 33 (OS) years. Results The mRNA data of ESR1 and PGR distributed bimodally, patterns confirmed in an independent cohort. Kappa-values between all methods were 0.76 and 0.79 for ER and PR respectively. Tamoxifen improved RFi in patients with ER-positive (ER+) or PR-positive (PR+) tumors (Hazard Ratio (HR) and 95% confidence interval (CI)), cytosol-ER + 0.53 (0.36–0.79); IHC-ER + 0.55 (0.38–0.79); GEX-ER + 0.54 (0.37–0.77); cytosol-PR + 0.49 (0.34–0.72); IHC-PR + 0.58 (0.40–0.85); GEX-PR + 0.55 (0.38–0.80)). Results were similar for OS. Conclusion Cytosol-based methods, IHC, and GEX analysis can all identify patients that benefit from two years of tamoxifen with equal performance, indicating that GEX data might be used to guide adjuvant tamoxifen therapy. The trial is registered on ISRCTN: ISRCTN12474687