316P - Differential long-term benefit of 2-year adjuvant tamoxifen therapy for luminal-type breast cancer: Insights from a 20-year follow-up analysis of the STO trials

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Swedish Research Council (Vetenskapsrådet), Swedish Research Council for Health, Working life and Welfare (FORTE), ALF medicine, Gösta Milton Donation Fund (Stiftelsen Gösta Miltons donationsfond), Swedish Cancer Society (Cancerfonden), Stockholm Cancer Society (Cancerföreningen iStockholm).

Disclosure

L.J. Van't Veer: Financial Interests, Institutional, Leadership Role, LJV is a cofounder, stockholder, and part-time employee of Agendia.: Agendia. All other authors have declared no conflicts of interest.