The effect of endocrine therapy omission on survival in ER-negative PR-low (1–10%) early-stage breast cancer treated with chemotherapy.

521 Background: The effect of endocrine therapy omission on outcomes in breast cancer (BC) with low progesterone receptor (PR) expression (1–10%) is unknown. Previously, omitting adjuvant endocrine therapy in estrogen receptor (ER)-low (1–10%) BC was associated with worse survival (1), but whether this is also true for PR 1–10% (PR-low) BC has not been studied. We analyzed outcomes for omission of endocrine therapy in patients with ER-negative PR-low stage I–III BC who received chemotherapy. Methods: We identified 46,704 patients from the National Cancer Database (diagnosed 2018–2020) with PR 1–10% stage I–III BC, of whom 3651 (7.8%) were ER-negative. Of these, 2,915 (79.8%) received chemotherapy. After excluding incomplete data for covariates, 2,796 remained for analysis. Cox proportional hazards models were used to analyze overall survival (OS). Multivariate Cox regression and propensity score matching were performed to account for confounding by age, stage, comorbidity score, HER2 status, year of diagnosis, and grade. This study protocol was developed and reviewed by oncology faculty prior to implementation. Results: Of the final cohort of 2,796 ER-negative PR-low BC patients, 73.6% were HER2-negative and 85.0% were high grade. Stage distribution was 34.8% stage I, 43.6% stage II, and 21.6% stage III. Endocrine therapy was omitted in 2,051 (73.4%). OS was 93.9% (95% CI 93.0–94.9%) at 2 years and 86.1% (95% CI 84.3–87.9%) at 4 years, with 267 total deaths. In the univariate (unadjusted) analysis, omission of endocrine therapy was associated with worse 4-year OS (hazard ratio [HR] 1.84, 95% CI 1.34–2.53, p<0.001). In the multivariate (adjusted) analysis, the HR was 1.72 (95% CI 1.25–2.37, p<0.001). Interaction testing for endocrine therapy and HER2 status was not significant. To account for possible pandemic impacts on OS, a sensitivity analysis of 2,639 patients (after excluding those who did not survive six months beyond definitive surgery) was performed and yielded a HR of 1.50 (95% CI 1.08–2.10, p=0.016). After propensity score matching of 1,490 ER-negative PR-low BC patients (matched by age, stage, comorbidity score, HER2 status, year of diagnosis, and grade), omission of endocrine therapy was still associated with worse 4-year OS (HR 1.63, 95% CI: 1.12–2.36, p=0.010). In contrast, omission of endocrine therapy in matched ER-negative PR-negative (instead of PR-low) BC patients was not associated with worse OS (HR 1.12, 95% CI: 0.92–1.37, p=0.27). Conclusions: In ER-negative PR-low (1–10%) early-stage BC treated with chemotherapy, omission of endocrine therapy may be associated with worse overall survival, suggesting that endocrine therapy could improve survival in ER-negative BC patients even with only low (1–10%) PR expression. Further investigation is recommended as this retrospective study design cannot establish causality. 1. Choong, 2024, JCO .