Long-term benefit from adjuvant tamoxifen therapy for ER+ HER2- breast cancer by PR positivity.

We aimed to evaluate the long-term tamoxifen benefit by progesterone receptor (PR) levels in postmenopausal lymph node-negative breast cancer patients with estrogen receptor (ER)-positive/human epidermal growth factor receptor 2-negative (HER2) tumors in the STO-3 randomized trial. This is a secondary analysis of the STO-3 trial including 559 postmenopausal breast cancer patients by PR levels. Patients were randomly assigned to at least 2 years of adjuvant tamoxifen therapy (40 mg once daily) versus no endocrine therapy in the Stockholm (STO)-3 trial. Twenty-five-year distant recurrence-free interval (DRFI) was assessed by Kaplan-Meier, multivariable Cox proportional hazard regression, and multivariable time-varying analyses. Univariable Kaplan-Meier analysis showed a significant long-term tamoxifen benefit for PR-positive disease using a threshold of 10% or greater (DRFI, tamoxifen treated 85% vs. control 68%; p < .0001). Similarly, patients with high PR gene expressing tumors had a significant long-term tamoxifen therapy benefit (DRFI, tamoxifen treated 84% vs. control 66%; log-rank p < .001). In contrast, we report no significant therapy benefit for patients with PR-negative disease (DRFI, tamoxifen treated 79% vs. control 70%; log-rank p = .14) or low PR gene expression (DRFI, tamoxifen treated 82% vs. control 74%; log-rank p = .17). Multivariable Cox proportional hazard regression modelling confirmed the univariable findings for PR-positive disease (HR = 0.37; 95% CI [0.23-0.61]). Time-varying analysis revealed a treatment benefit for PR-positive disease up to 25 years (HR = 0.35; 95% CI [0.16-0.79]), but not for patients with PR-negative tumors. PR-positivity as determined by immunohistochemistry predicted long-term benefit from adjuvant tamoxifen in lymph node-negative postmenopausal breast cancer patients with ER+/HER2- tumors.