Effect of Hormone Resistance Type on First-Line Treatment Selection in ER+/HER2-Negative Metastatic Breast Cancer

Abstract

Introduction. The optimal first-line hormone therapy (HT) regimen for HR+/HER2− metastatic breast cancer (mBC) remains a topic of debate. The SONIA trial demonstrated no significant benefit from adding CDK4/6 inhibitors (CDK4/6i) to first-line therapy for all patients, yet criteria for identifying patients who require combination HT have not been established. The type of hormone resistance (HR) represents a biologically plausible candidate for such a predictive marker.

Aim. To evaluate the impact of HR type (no resistance [HR0], primary resistance [HR1], secondary resistance [HR2]) on progression-free survival (PFS) and objective response rate (ORR) during first-line treatment of luminal mBC, and to determine the predictive value of HR type when comparing HT monotherapy versus combination HT (CDK4/6i + HT) in real-world clinical practice.

Materials and Methods. This retrospective study included 90 patients with HR+/HER2− mBC classified as HR0 (n=28), HR1 (n=21), and HR2 (n=41). In the first-line setting, 61 patients received combination HT and 29 received monotherapy. PFS was analyzed using the Kaplan–Meier method and the log-rank test. Group comparability was assessed using the Mann–Whitney U test, χ² test, and Fisher's exact test.

Results. HR type was a significant prognostic factor (p=0.0017): median PFS was 28 months for HR0, 22 months for HR2, and 13 months for HR1. Despite a worse baseline prognostic profile in the primary resistance group, combination HT significantly outperformed monotherapy in median PFS (16 months vs. 9 months; p=0.028); ORR was 0% with HT monotherapy versus 16.7% with combination HT. In secondary resistance, a clinically meaningful but statistically non-significant benefit was observed (23 months vs. 16.5 months; p=0.47). In the HR0, no difference in PFS was found (32 months vs. 28 months; p=0.99).

Conclusion. Primary HR predicts a significant benefit from combination HT and supports the mandatory use of CDK4/6i in this patient subgroup. In HR0, aromatase inhibitor monotherapy achieves high PFS comparable to that of combination therapy. The non-comparability of groups for several prognostic factors suggests that the observed effect of combination HT may be underestimated, and the results should be interpreted with consideration of the retrospective, observational study design.