Baseline risk variability by eligibility criteria in Cohort 1 of the monarchE trial for high-risk HR-positive, HER2-negative breast cancer

TL;DR

This study shows that high-risk breast cancer patients in the monarchE trial have varying recurrence risks based on specific criteria, which could help tailor treatment.

Contribution

The study identifies distinct prognostic differences among high-risk breast cancer subgroups in the monarchE trial criteria.

Findings

5-year iDFS rates varied significantly across subgroups, with ≥N2 having the lowest at 77.3%.

N1 + G3, ≥N2, and neoadjuvant chemotherapy were identified as poor prognostic factors.

The study emphasizes the need for individualized risk assessment to optimize treatment benefits.

Abstract

Baseline recurrence risk increasingly guides adjuvant endocrine therapy for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer (BC). The monarchE trial demonstrated the benefits of adding abemaciclib to endocrine therapy for high-risk patients. However, differences in baseline recurrence risks within monarchE Cohort 1 subgroups and their impact on absolute benefit remain unclear. This study assessed these prognostic differences.

We retrospectively analysed 989 patients with HR-positive, and HER2-negative BC who underwent surgery between January 2017 and August 2019 at our institution. Patients were categorised into four groups: non-eligible (not meeting monarchE criteria), N1 + >5 cm (1–3 lymph node metastases with tumours >5 cm), N1 + G3 (1–3 lymph node metastases with Grade 3 tumours), and ≥N2 (≥4 lymph node metastases). Survival outcomes, including invasive disease-free survival (iDFS), distant disease-free survival, and overall survival, were analysed using Kaplan–Meier and Cox proportional hazards models.

The 5-year iDFS rates were 94.7% (non-eligible), 88.9% (N1 + >5 cm), 83.3% (N1 + G3), and 77.3% (≥N2) (p < 0.001). Multivariate analysis identified N1 + G3 HR3.38, p = 0.005), ≥N2 (HR 3.39, p < 0.001), and neoadjuvant chemotherapy (HR 2.71, p = 0.003) as poor prognostic factors.

This study highlights the prognostic variability among high-risk subgroups aligned with monarchE Cohort 1 criteria. Individualized risk assessment will be key to optimizing the benefit of adjuvant therapy in HR-positive, HER2-negative breast cancer.

The online version contains supplementary material available at 10.1007/s12282-025-01747-x.

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