Work

Parity, breastfeeding, and reproductive timing are associated with tumour-infiltrating lymphocytes in hormone receptor-negative breast cancer: a population-based cohort study

Year: 2026

Type: article

Abstract: Background Tumour-infiltrating lymphocytes (TILs) are established biomarkers of breast cancer immunogenicity and prognosis. Reproductive events induce durable immunological remodelling of the breast, but whether TIL levels at diagnosis reflect the immunological imprint of these events remains unclear. Materials and methods We included women diagnosed with invasive breast cancer between 1978 and 2012 in the Energy Balance and Breast Cancer Aspects throughout Life study, a substudy of the population-based Tromsø Study (Norway). Prediagnostic host factors were obtained. TILs were scored on an ordinal scale (1-4). Associations between host factors and the TIL score were analysed using ordinal logistic regression with interaction terms for hormone receptor (HR) status. Breast cancer-specific mortality was evaluated using Kaplan–Meier methods and Cox regression. Results A total of 425 women were included [median age at diagnosis 56.0 years, 360 (87.6%) parous], of whom 84 (19.8%) had HR-negative tumours. Among HR-negative cases, parity [odds ratio (OR) 10.14, 95% confidence interval (CI) 1.97-52.22], longer breastfeeding duration [OR 1.87 per standard deviation (SD), 95% CI 1.10-3.17], and higher age at first birth (OR 1.79 per SD, 95% CI 1.06-3.01) were associated with higher TIL scores, whereas higher mean arterial pressure (OR 0.59 per SD, 95% CI 0.41-0.86) was inversely associated. Significant interactions with HR status were observed for parity and breastfeeding duration. No associations were observed in HR-positive tumours. High-TIL levels (scores 3-4 versus 1-2) were associated with lower breast cancer-specific mortality in HR-negative tumours (adjusted hazard ratio 0.32, 95% CI 0.14-0.72) but not in HR-positive disease (hazard ratio 0.98, 95% CI 0.58-1.68; P interaction = 0.023). Conclusions These findings suggest that reproductive history and timing may shape the tumour immune microenvironment over the life course. If confirmed in larger studies, TILs may represent an intermediate phenotype linking upstream host characteristics to downstream clinical outcomes in breast cancer.

Source: ESMO Open

DOI: 10.1016/j.esmoop.2026.108604