Patients with estrogen receptor (ER)-positive breast cancer have a long-term risk of distant recurrence, but the underlying reasons remain unclear. Therefore, studies with long-term follow-up are essential to understand endocrine therapy benefit. Here, we investigate tamoxifen therapy benefit in Luminal-type breast cancer as defined by the BluePrint® and Genomic Risk signatures in the Stockholm tamoxifen (STO)-trials with 20-year follow-up.

Secondary analysis of the STO-trials including both pre- and postmenopausal patients of high and low clinical risk with a complete 20-year follow-up. The enrolled patients were randomly assigned to at least 2 years of adjuvant endocrine therapy or no endocrine therapy (control). In this study only patients assigned to 2 years of tamoxifen or no endocrine therapy were included. Patients with ER-positive and Luminal-type tumors (n=822), as assessed with the BluePrint® and Genomic Risk signatures, were included. Long-term (20 years) distant recurrence-free interval (DRFI) was assessed by Kaplan-Meier, Cox regression, and time-varying analyses.

Luminal Low-Risk patients had a significant long-term tamoxifen therapy benefit (Kaplan-Meier: Treated 74% vs. Control 61%, log-rank P=0.0047; Multivariable: DRFI HR=0.53; 95% CI [0.37-0.77]), whereas Ultralow (Kaplan-Meier: Treated 77% vs. Control 74%; log-rank P=0.5; DRFI HR=0.75; 95% CI [0.29-1.91]) and Luminal High-Risk patients had no significant benefit (Kaplan-Meier: Treated 54% vs. Control 50%; log-rank P=0.39; Multivariable: DRFI HR=0.77; 95% CI [0.51-1.12]). Time-varying analysis revealed a long-term treatment benefit for Luminal Low-Risk patients up to 20-years (HR= 0.44, 95% CI [0.24-0.81]), but not for Luminal High-Risk patients.

Patients with Luminal Low-Risk breast cancer had a long-term benefit from 2 years of adjuvant tamoxifen up to 20 years beyond primary diagnosis. No significant benefit was seen for Ultralow or Luminal High-Risk patients. This highlights the importance of extended follow-up to understand treatment benefit and the importance of individualized management for ER-positive patients.