Prognostic impact of estrogen and progesterone receptor expression disparity in early-stage HR+/HER2- breast cancer.

Abstract

e12534 Background: In hormone receptor-positive, HER2-negative early-stage breast cancer (HR+/HER2- EBC), the biological characteristics and therapeutic response to endocrine treatment are fundamentally shaped by the synergistic interplay between estrogen receptor (ER) and progesterone receptor (PR). Nevertheless, the role of discordant expression levels between ER and PR—termed ΔER-PR—remains poorly studied, and its effect on patient outcomes is unclear. Methods: This large-scale, multicenter retrospective study analyzed data from 3521 patients with HR+/HER2- EBC, treated across four institutions between January 2013 and June 2019. The continuous variable ΔER-PR was calculated, and its optimal cut-off value was determined using X-tile software, with subsequent validation via the survminer package in R. Based on this threshold, patients were categorized into two groups for comparative analysis. To ensure balanced baseline characteristics and minimize selection bias, propensity score matching (PSM) was employed to adjust for potential confounders. The primary endpoint, disease-free survival (DFS), was evaluated using Kaplan-Meier (KM) survival curves, and both univariate and multivariate Cox proportional hazards regression analyses were conducted to identify independent prognostic factors. Results: The optimal cut-off for ΔER-PR was identified as 25%. This stratified patients into a “Discordant Expression Group” (ΔER-PR > 25%) and a “Concordant Expression Group” (ΔER-PR ≤ 25%). Before PSM, the cohorts consisted of 1417 and 2104 patients, respectively. After PSM, 2236 patients were equally matched (1118 per group). KM survival analysis consistently demonstrated significantly inferior DFS in the Discordant Expression Group compared to the Concordant Group, both before and after matching (all P < 0.001). Multivariate Cox regression analyses confirmed that belonging to the Discordant Expression Group was an independent adverse prognostic factor for DFS (pre-PSM: HR 1.52, 95% CI 1.27–1.81, P < 0.001; post-PSM: HR 1.47, 95% CI 1.21–1.79, P < 0.001). Subgroup analyses across various patient strata further corroborated the consistent negative prognostic impact of significant ER/PR expression disparity. Conclusions: This study demonstrates that a disparity in ER and PR expression (ΔER-PR > 25%) is associated with inferior prognosis in HR+/HER2- EBC, underscoring that imbalance between these receptors may substantially influence the effectiveness of endocrine therapy.