Survival analysis of adjuvant endocrine therapy in HER2 positive early breast cancer patients with low ER positivity

Background: Optimal treatment strategies for early-stage human epidermal growth factor receptor 2 (HER2) positive breast cancer with low estrogen receptor (ER) expression (1–9%) remain unclear. While endocrine therapy (ET) is standard for ER-positive disease, its benefit in ER-low tumors, particularly with concurrent HER2 overexpression, is less established. Methods: We conducted a retrospective cohort study using Taiwan’s national cancer registry, identifying 10,408 patients with HER2-positive early breast cancer diagnosed between 2011 and 2019. Of these, 1436 (15.48%) had low ER positivity. Patients were stratified by ER level (1–9% vs. ≥10%) and ET use. Overall survival (OS), breast cancer-specific survival (BCSS), and recurrence-free survival (RFS) were evaluated via Kaplan-Meier and Cox regression analyses. Progesterone receptor (PR) status was also assessed. Results: Adjuvant ET significantly improved OS, BCSS, and RFS in both ER subgroups (all p < 0.05). In ER-low patients, ET was associated with improved OS (90.16% vs. 85.55%, p = 0.0082), BCSS (93.91% vs. 89.71%, p = 0.0047), and RFS (91.24% vs. 88.21%, p = 0.0316). On multivariate analysis, PR positivity—not ER level—was an independent predictor of improved outcomes. Notably, PR-positive, ER-low patients had better OS with ET (92.08% vs. 86.69%, p = 0.0216). Conclusion: Adjuvant ET provides meaningful survival benefits in HER2-positive early breast cancer with low ER expression, particularly in PR-positive tumors. Despite this, 41.92% of eligible ER-low patients did not receive ET, highlighting a treatment gap. PR status may guide ET decisions, supporting individualized treatment approaches.