What question did this study set out to answer?

This study aims to explore the correlation between homologous recombination deficiency (HRD), tumor-infiltrating lymphocytes (TILs), and clinical outcomes in HR+/HER2− breast cancer.

June 20, 2026Open Access

Homologous recombination deficiency correlates with tumor-infiltrating lymphocytes and predicts patient outcomes in hormone receptor-positive/HER2-negative breast cancer

Key Points

This study aims to explore the correlation between homologous recombination deficiency (HRD), tumor-infiltrating lymphocytes (TILs), and clinical outcomes in HR+/HER2− breast cancer.
Retrospective multicenter cohort study of 365 patients with HR+/HER2− breast cancer.
HRD was assessed using the Shallow HRD algorithm on whole-genome sequencing, while TILs were evaluated using the MD Anderson system.
Statistical analyses included Spearman correlation, Kaplan–Meier survival analysis, and multivariable Cox regression.
HRD scores showed a significant inverse correlation with TILs (Spearman rho = -0.13, p = 0.031).
HRD-high patients exhibited inferior 10-year survival rates compared to HRD-low (IDFS: 31.0% vs. 57.9%, HR = 2.36; OS: 48.7% vs. 79.0%, HR = 2.79; p < 0.0001).
HRD confirmed as an independent prognostic predictor (IDFS HR = 2.03, p < 0.01).

Abstract

Background: Hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−) breast cancer represents the most prevalent molecular subtype but demonstrates pronounced biological and clinical heterogeneity. Homologous recombination deficiency (HRD) and tumor-infiltrating lymphocytes (TILs) have recently emerged as key determinants of prognosis and immune activity, but their interplay in this subtype remains understudied. Objectives: To assess the relationship between HRD, TILs, and clinical outcomes in HR+/HER2− breast cancer and validate the prognostic value of HRD. Design: Retrospective multicenter cohort study. Methods: A total of 365 patients (332 with available TILs data) from three institutions were enrolled. HRD was quantified using Shallow HRD algorithm on low-depth whole-genome sequencing (threshold: score ⩾6). TILs were evaluated by the MD Anderson system (⩾10% classified as high). Spearman correlation, Kaplan–Meier survival analysis, and multivariable Cox regression were performed. Results: HRD scores were inversely correlated with TILs (Spearman rho = −0.13, p = 0.031). HRD-high patients had significantly inferior 10-year survival (invasive disease-free survival (IDFS): 31.0% vs 57.9%, hazard ratio (HR) = 2.36; distant recurrence-free survival (DRFS): 34.1% vs 61.1%, HR = 2.48; overall survival (OS): 48.7% vs 79.0%, HR = 2.79; p < 0.0001). HRD was confirmed as an independent prognostic predictor (IDFS HR = 2.03, DRFS HR = 2.16, OS HR = 2.15; p < 0.01). No significant survival benefit from anthracycline-based chemotherapy was observed in HRD-high tumors (HR = 1.32, p = 0.451). High TILs showed no significant association with survival outcomes in this cohort. Conclusion: HRD represents a reliable independent prognostic biomarker in HR+/HER2− breast cancer in this cohort, with an inverse association with TILs suggesting immune evasion. Its potential impact on prognosis and treatment requires further validation in prospective clinical trials.

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